Effect of Spinal Manipulative and Mobilization Therapies in Young Adults With Mild to Moderate Chronic Low Back Pain: A Randomized Clinical Trial | Complementary and Alternative Medicine | JAMA Network Open | JAMA Network
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Visual Abstract. Effect of Spinal Manipulative and Mobilization Therapies in Young Adults with Mild to Moderate Chronic Low Back Pain
Effect of Spinal Manipulative and Mobilization Therapies in Young Adults with Mild to Moderate Chronic Low Back Pain
Figure 1.  CONSORT Diagram
CONSORT Diagram
Figure 2.  Change in Self-reported Pain and Disability Scores
Change in Self-reported Pain and Disability Scores

A, Self-reported assessment of average pain during the last 7 days (Numerical Pain Rating Scale score; range, 0-10, with higher scores indicating greater pain). B, Self-reported disability (Roland-Morris Disability Questionnaire; range, 0-24, with higher scores indicating greater disability). Means and 95% CIs (error bars) are plotted for ratings collected at the initial visit, 72 hours after completing 3 weeks of treatment (ie, primary end point), and 4 weeks after treatment completion (ie, follow-up). The plots are offset along the time axis for visual clarity.

Table 1.  Baseline Participant Characteristics
Baseline Participant Characteristics
Table 2.  Relationship Between Treatment Expectancy and Observed Pain Changes by Study Group
Relationship Between Treatment Expectancy and Observed Pain Changes by Study Group
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Paige  NM, Miake-Lye  IM, Booth  MS,  et al.  Association of spinal manipulative therapy with clinical benefit and harm for acute low back pain: systematic review and meta-analysis.   JAMA. 2017;317(14):1451-1460. doi:10.1001/jama.2017.3086PubMedGoogle ScholarCrossref
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Bronson  MA, Smith  DL, Tuchin  P.  Spinal manipulation is beneficial for nonchronic low back pain.   Am J Emerg Med. 2017;35(10):1576-1577. doi:10.1016/j.ajem.2017.04.048PubMedGoogle ScholarCrossref
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Schneider  M, Haas  M, Glick  R, Stevans  J, Landsittel  D.  Comparison of spinal manipulation methods and usual medical care for acute and subacute low back pain: a randomized clinical trial.   Spine (Phila Pa 1976). 2015;40(4):209-217. doi:10.1097/BRS.0000000000000724PubMedGoogle ScholarCrossref
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Qaseem  A, Wilt  TJ, McLean  RM, Forciea  MA; Clinical Guidelines Committee of the American College of Physicians.  Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians.   Ann Intern Med. 2017;166(7):514-530. doi:10.7326/M16-2367PubMedGoogle ScholarCrossref
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Merepeza  A.  Effects of spinal manipulation versus therapeutic exercise on adults with chronic low back pain: a literature review.   J Can Chiropr Assoc. 2014;58(4):456-466.PubMedGoogle Scholar
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Licciardone  JC, Gatchel  RJ, Aryal  S.  Recovery from chronic low back pain after osteopathic manipulative treatment: a randomized controlled trial.   J Am Osteopath Assoc. 2016;116(3):144-155. doi:10.7556/jaoa.2016.031PubMedGoogle ScholarCrossref
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Xia  T, Long  CR, Gudavalli  MR,  et al.  Similar effects of thrust and nonthrust spinal manipulation found in adults with subacute and chronic low back pain: a controlled trial with adaptive allocation.   Spine (Phila Pa 1976). 2016;41(12):E702-E709. doi:10.1097/BRS.0000000000001373PubMedGoogle ScholarCrossref
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Castro-Sánchez  AM, Lara-Palomo  IC, Matarán-Peñarrocha  GA,  et al.  Short-term effectiveness of spinal manipulative therapy versus functional technique in patients with chronic nonspecific low back pain: a pragmatic randomized controlled trial.   Spine J. 2016;16(3):302-312. doi:10.1016/j.spinee.2015.08.057PubMedGoogle ScholarCrossref
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Lopez-Lopez  A, Alonso Perez  JL, González Gutierez  JL,  et al.  Mobilization versus manipulations versus sustain apophyseal natural glide techniques and interaction with psychological factors for patients with chronic neck pain: randomized controlled trial.   Eur J Phys Rehabil Med. 2015;51(2):121-132.PubMedGoogle Scholar
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Paanalahti  K, Holm  LW, Nordin  M,  et al.  Three combinations of manual therapy techniques within naprapathy in the treatment of neck and/or back pain: a randomized controlled trial.   BMC Musculoskelet Disord. 2016;17:176. doi:10.1186/s12891-016-1030-yPubMedGoogle ScholarCrossref
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Gatterman  MI, Cooperstein  R, Lantz  C, Perle  SM, Schneider  MJ.  Rating specific chiropractic technique procedures for common low back conditions.   J Manipulative Physiol Ther. 2001;24(7):449-456. doi:10.1016/S0161-4754(01)75655-2PubMedGoogle ScholarCrossref
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Hondras  MA, Long  CR, Cao  Y, Rowell  RM, Meeker  WC.  A randomized controlled trial comparing 2 types of spinal manipulation and minimal conservative medical care for adults 55 years and older with subacute or chronic low back pain.   J Manipulative Physiol Ther. 2009;32(5):330-343. doi:10.1016/j.jmpt.2009.04.012PubMedGoogle ScholarCrossref
18.
Clark  BC, Russ  DW, Nakazawa  M,  et al.  A randomized control trial to determine the effectiveness and physiological effects of spinal manipulation and spinal mobilization compared to each other and a sham condition in patients with chronic low back pain: Study protocol for The RELIEF Study.   Contemp Clin Trials. 2018;70:41-52. doi:10.1016/j.cct.2018.05.012PubMedGoogle ScholarCrossref
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Childs  JD, Fritz  JM, Flynn  TW,  et al.  A clinical prediction rule to identify patients with low back pain most likely to benefit from spinal manipulation: a validation study.   Ann Intern Med. 2004;141(12):920-928. doi:10.7326/0003-4819-141-12-200412210-00008PubMedGoogle ScholarCrossref
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Devilly  GJ, Borkovec  TD.  Psychometric properties of the credibility/expectancy questionnaire.   J Behav Ther Exp Psychiatry. 2000;31(2):73-86. doi:10.1016/S0005-7916(00)00012-4PubMedGoogle ScholarCrossref
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Dougherty  PE, Karuza  J, Savino  D, Katz  P.  Evaluation of a modified clinical prediction rule for use with spinal manipulative therapy in patients with chronic low back pain: a randomized clinical trial.   Chiropr Man Therap. 2014;22(1):41. doi:10.1186/s12998-014-0041-8PubMedGoogle ScholarCrossref
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Manogharan  S, Kongsted  A, Ferreira  ML, Hancock  MJ.  Do older adults with chronic low back pain differ from younger adults in regards to baseline characteristics and prognosis?   Eur J Pain. 2017;21(5):866-873. doi:10.1002/ejp.989PubMedGoogle ScholarCrossref
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Machado  LA, Kamper  SJ, Herbert  RD, Maher  CG, McAuley  JH.  Imperfect placebos are common in low back pain trials: a systematic review of the literature.   Eur Spine J. 2008;17(7):889-904. doi:10.1007/s00586-008-0664-3PubMedGoogle ScholarCrossref
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Puhl  AA, Reinhart  CJ, Doan  JB, Vernon  H.  The quality of placebos used in randomized, controlled trials of lumbar and pelvic joint thrust manipulation-a systematic review.   Spine J. 2017;17(3):445-456. doi:10.1016/j.spinee.2016.11.003PubMedGoogle ScholarCrossref
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    3 Comments for this article
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    A moratorium on monotherapy on unclassified (undiagnosed) low back pain
    Donald Murphy, DC | Alpert Medical School of Brown University
    This is a well-designed, well-performed, well-written study that is part of a long line of clinical trials for LBP that are of little to no usefulness in the field of spine related disorders. I would recommend a moratorium on clinical trials that study a single modality of treatment in a population of patients with LBP without consideration of 1) the specific features and needs of each patient and 2) the context (1) in which the treatment is applied. Attempts to apply a one-size-fits-all approach to LBP, after decades of study, have provided very little benefits in terms of informing clinicians as to the best way to approach individual patients. This is not a criticism of the professionals who performed this study, but on the unhelpful manner in which clinical trials on the management of patients with LBP have been carried out for a long time.

    I realize that an attempt to classify, using the clinical prediction rule, was done in this study (unlike the majority of other clinical trials in LBP). So my comment regarding patients being "unclassified (undiagnosed)" apply more generally in the field, not to this specific study.

    1. Testa M, Rossettini G: Enhance placebo, avoid nocebo: How contextual factors affect physiotherapy outcomes. Man Ther 2016, 24:65-74
    CONFLICT OF INTEREST: None Reported
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    A biopsychosocial approach to managing chronic low back pain is essential now and in future clinical trial designs
    David Byfield, BSc Hons, DC, MPhil | Neurovascular Research Laboratory, School of Health, Sport and Professional Practice, Faculty of Life Sciences and Education, University of South Wales, WalesUK
    We would like to congratulate Thomas et al. for their work. However, in terms of the design, this trial was an efficacy study and not an effectiveness study to evaluate the two interventions for the treatment of chronic low back pain (LBP). These two types of trials are often poorly understood as they serve distinct purposes. Efficacy studies investigate the benefits and harms of an intervention under highly controlled conditions requiring a deviation from routine clinical practice due to restrictions placed on the study sample, ie strict inclusion exclusion criteria. Effectiveness studies evaluate interventions that more closely resemble real-life clinical settings with more varied patient populations, less standardised protocols and interventions delivered in a everyday clinical environment. The authors also haven’t considered the nature and course of chronic LBP by employing only a 4 week follow up from baseline. LBP is a persistant and reoccurring condition and the study timeline was too short to evaluate the effect of the interventions over time. Numerous randomised controlled trials of varying methodological quality and size have examined the benefits and harms of manual therapy for the treatment of LBP. A recent systematic review by Rubenstein et al. (2019) suggested that future clinical trials of manual therapy for chronic LBP are not necessary unless they contain an innovative approach, are well designed, include an economic evaluation and contain qualitative information about patient context, their beliefs and preferences.

    Thomas et al. have also overlooked the seminal work published in the Lancet Low Back Series (Hartvigsen et al., Foster et al., Buchbinder et al., 2018). These publications were the turning point in the understanding and management of chronic LBP and a key message was the assessment and management of LBP should be underpinned by a biopsychosocial model. An awareness of this model has greatly advanced the understanding of the prognostic significance of psychosocial factors in individual patients in a real clinical setting. Continuing to investigate the effectiveness of a single modality in isolation only perpetuates a biomedical approach and underestimating the contextual parameters that accompany this complex clinical presentation.

    Therefore, the conclusion of this study that spinal manipulation or spinal mobilisation are not effective for the treatment of chronic LBP is also out of step with contemporary clinical guidelines for LBP, including, i) the Danish Health Authority Guidelines (2018), ii) the American College of Physicians Guidelines (2017), iii) the National Institute of Clinical Excellence UK (NICE)) Guidelines (2016), which recommend spinal manipulative therapy for both acute and chronic LBP of all ages in conjunction with other interventions such as exercise, advice and education in a non-pharmacological approach. Therefore, we recommend that in future studies reporting interventions for LBP must reflect best practice and focus on the patients’ context and modifiable biopsychosocial factors that influence pain and disability facilitated by education and active self-management protocols.

    References

    Rubenstein SM et al. M. Benefits and harms of spinal manipulative therapy for the treatment of chronic low back pain: systematic review and meta-analysis of randomised controlled trials. British Medical Journal. 2019; 364:l689

    Singal AG et al. A. A Primer on Effectiveness and Efficacy Trials. Clinical and Translational Gastrooenterology. 2014;5, e45;doi:10.1038/ctg.2013.13
    CONFLICT OF INTEREST: None Reported
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    To Enhance Translation Potential Consider Updating Conclusion and Title
    David Elton, D.C. | UnitedHealth Group
    This research was thoughtfully designed, carefully executed and contains important insights. The title and primary conclusion would benefit from an update to more closely reflect the research performed.

    The study found 6 visits of spinal manipulation or mobilization delivered by Doctors of Osteopathy (DO) and Physical Therapists (PT) as a monotherapy was no better than a placebo monotherapy for 18 to 45-year-old patients with mild to moderate chronic low back pain. Readers may infer from the paper’s title and conclusion extrapolate that this important insight, which could be true, to all spinal manipulation or mobilization.

    In
    addition to the growing body of high-quality research in the public domain, including JAMA Network Open, experience from approximately 1 million complete episodes of non-surgical back pain ending in 2017-2019 in 18 to 45-year-old patients in a commercially insured population provides some additional context for this comment:

    • ~10% of all spinal manipulation or mobilization is performed by DOs or PTs, and is infrequently provided as a monotherapy
    • ~90% of all spinal manipulation or mobilization is performed by Doctors of Chiropractic (DC) using Chiropractic Manipulative Treatment (CMT) codes, and is infrequently provided as a mono-therapy
    • 1-6 visits of CMT provided alone or in combination with other services is associated with several beneficial total episode of care attributes when compared to overall performance for the entire sample of 1 million episodes, a few examples include:
    • 1-6 visits of CMT is associated with lower total episode cost, smaller number of different providers seen during the episode, lower rates of Rx classes like opioids, NSAIDs and skeletal muscle relaxants, and lower rates of spinal imaging and injections.
    • CMT is the only form of spinal manipulation or mobilization that is associated with lower total episode cost when 1-6 visits are provided and is associated with higher total episode cost if never provided.
    • While these are not true clinical outcome measures, they do provide a proxy for potential clinical benefits of CMT.
    • Seemingly consistent with the paper’s findings, 1-6 visits of spinal manipulation performed by a DO or mobilization performed by a PT is not associated with the same beneficial total episode of care attributes observed with 1-6 visits of CMT:
    • 1-6 visits of spinal manipulation performed by a DO or mobilization performed by a PT is associated with higher total episode cost, higher number of different providers seen during the episode, and higher rates of imaging and injection when compared to overall performance for the entire sample of 1 million episodes.
    • Like CMT, 1-6 visits of spinal manipulation performed by a DO or mobilization performed by a PT alone or in combination with other services is associated with lower rates of Rx classes like opioids, NSAIDs and skeletal muscle relaxants.

    The paper's finding that spinal manipulation or mobilization delivered by a DO or PT as monotherapy, while uncommon, is no better than an even less commonly provided placebo monotherapy is an important advance in our understanding of treatment mild to moderate chronic back pain. The paper did not explore either; a. what is by far the most common form of spinal manipulation, Chiropractic Manipulative Treatment, or b. spinal manipulation/mobilization performed by any provider in combination with other services.
    CONFLICT OF INTEREST: None Reported
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    Original Investigation
    Orthopedics
    August 5, 2020

    Effect of Spinal Manipulative and Mobilization Therapies in Young Adults With Mild to Moderate Chronic Low Back Pain: A Randomized Clinical Trial

    Author Affiliations
    • 1Department of Physical Therapy, Virginia Commonwealth University, Richmond
    • 2Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond
    • 3Division of Physical Therapy, Ohio University School of Rehabilitation and Communication Sciences, Athens
    • 4Ohio Musculoskeletal and Neurological Institute, Ohio University, Athens
    • 5Department of Biomedical Sciences, Ohio University, Athens
    • 6Morsani College of Medicine, University of South Florida School of Physical Therapy and Rehabilitation Sciences, Tampa
    • 7Department of Psychology, Ohio University, Athens
    • 8Applied Biostatistics Laboratory, University of Michigan School of Nursing, Ann Arbor
    • 9Feinberg School of Medicine, Department of Physical Therapy and Human Movement Sciences, Northwestern University, Chicago, Illinois
    JAMA Netw Open. 2020;3(8):e2012589. doi:10.1001/jamanetworkopen.2020.12589
    Key Points español 中文 (chinese)

    Question  What is the comparative effectiveness of spinal manipulation compared with spinal mobilization relative to a placebo control in reducing pain and disability in chronic low back pain?

    Findings  In this randomized clinical trial that included 162 young adults, there was no difference in reduction of pain and disability when comparing spinal manipulation to spinal mobilization relative to the placebo control treatment.

    Meaning  Neither spinal manipulation nor mobilization appeared to be an effective intervention for young adults with mild to moderate chronic low back pain.

    Abstract

    Importance  Low back pain (LBP) is one of the most common reasons for seeking medical care. Manual therapy is a common treatment of LBP, yet few studies have directly compared the effectiveness of thrust (spinal manipulation) vs nonthrust (spinal mobilization) techniques.

    Objective  To evaluate the comparative effectiveness of spinal manipulation and spinal mobilization at reducing pain and disability compared with a placebo control group (sham cold laser) in a cohort of young adults with chronic LBP.

    Design, Setting, and Participants  This single-blinded (investigator-blinded), placebo-controlled randomized clinical trial with 3 treatment groups was conducted at the Ohio Musculoskeletal and Neurological Institute at Ohio University from June 1, 2013, to August 31, 2017. Of 4903 adult patients assessed for eligibility, 4741 did not meet inclusion criteria, and 162 patients with chronic LBP qualified for randomization to 1 of 3 treatment groups. Recruitment began on June 1, 2013, and the primary completion date was August 31, 2017. Data were analyzed from September 1, 2017, to January 20, 2020.

    Interventions  Participants received 6 treatment sessions of (1) spinal manipulation, (2) spinal mobilization, or (3) sham cold laser therapy (placebo) during a 3-week period.

    Main Outcomes and Measures  Coprimary outcome measures were the change from baseline in Numerical Pain Rating Scale (NPRS) score over the last 7 days and the change in disability assessed with the Roland-Morris Disability Questionnaire (scores range from 0 to 24, with higher scores indicating greater disability) 48 to 72 hours after completion of the 6 treatments.

    Results  A total of 162 participants (mean [SD] age, 25.0 [6.2] years; 92 women [57%]) with chronic LBP (mean [SD] NPRS score, 4.3 [2.6] on a 1-10 scale, with higher scores indicating greater pain) were randomized. Fifty-four participants were randomized to the spinal manipulation group, 54 to the spinal mobilization group, and 54 to the placebo group. There were no significant group differences for sex, age, body mass index, duration of LBP symptoms, depression, fear avoidance, current pain, average pain over the last 7 days, and self-reported disability. At the primary end point, there was no significant difference in change in pain scores between spinal manipulation and spinal mobilization (0.24 [95% CI, −0.38 to 0.86]; P = .45), spinal manipulation and placebo (−0.03 [95% CI, −0.65 to 0.59]; P = .92), or spinal mobilization and placebo (−0.26 [95% CI, −0.38 to 0.85]; P = .39). There was no significant difference in change in self-reported disability scores between spinal manipulation and spinal mobilization (−1.00 [95% CI, −2.27 to 0.36]; P = .14), spinal manipulation and placebo (−0.07 [95% CI, −1.43 to 1.29]; P = .92) or spinal mobilization and placebo (0.93 [95% CI, −0.41 to 2.29]; P = .17).

    Conclusions and Relevance  In this randomized clinical trial, neither spinal manipulation nor spinal mobilization appeared to be effective treatments for mild to moderate chronic LBP.

    Trial Registration  ClinicalTrials.gov Identifier: NCT01854892

    Introduction

    Low back pain is one of the most common reasons for seeking care from a physician, with total costs exceeding $100 billion annually in the US alone.1-3 These costs are driven primarily by 7% to 10% of patients who develop chronic low back pain. Manipulative therapies are a common conservative treatment approach for low back pain, with more than 18 million American adults receiving manipulative therapies at a total annual out-of-pocket cost of $3.9 billion.4

    Spinal manipulative treatments can be broadly classified as manipulation-based or mobilization-based techniques. Manipulation-based techniques apply a high-velocity, low-amplitude force to the spine and are often accompanied by an audible sound from 1 or more joints.5 In contrast, mobilization-based techniques use a low-velocity, low-force approach that generally does not produce audible joint sounds. Although the clinical effectiveness of manipulative therapy techniques for acute and subacute low back pain has been reported,6-8 the evidence on the effectiveness for reducing pain in patients with chronic low back pain is mixed.9-11 Reviews have generally found that manipulation is more effective compared with standard of care,6 but few studies have compared the clinical effectiveness of these 2 manipulative therapies,12-17 and existing studies have yielded discrepant results. Some studies indicate that manipulation-based techniques are more effective for low back pain compared with nonthrust techniques13,14,16; however, other studies report no significant difference in clinical outcomes between spinal manipulation and mobilization.12,15,17 Finally, most studies on manipulative therapies have used standard of care or waiting list controls as the comparison group.6 The current trial sought to use stronger control given the prevalence of both techniques in clinical practice and that understanding their relative effectiveness is an important and unresolved issue.

    Accordingly, the RELIEF (Researching the Effectiveness of Lumbar Interventions for Enhancing Function) Study was conducted as a phase II randomized clinical trial to compare the effectiveness of spinal manipulation, spinal mobilization, and placebo (sham laser) in the treatment of pain and disability among young adults with chronic low back pain.

    Methods
    Study Design

    This randomized clinical trial was a single-blinded (investigator-blinded), placebo-controlled, 3-arm, parallel-groups trial with repeated measurements. The Ohio University institutional review board approved this study, and written informed consent was obtained from all participants. The detailed study protocol (Supplement 1) is published18 and registered on ClinicalTrials.gov (NCT01854892). This study was conducted according to the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline. Recruitment began on June 1, 2013, and the primary completion date was August 31, 2017. Participants were randomized in a 1:1:1 ratio into 1 of 3 groups (Figure 1).

    Group 1 received spinal manipulation treatment 2 times per week for 3 weeks (spinal manipulation). Group 2 received spinal mobilization treatment 2 times per week for 3 weeks. The placebo group received sham cold laser treatment 2 times per week for 3 weeks. Randomization was stratified by sex, using a permuted block design, for the purpose of maintaining balance across treatment groups. This-computer generated randomization table was maintained by the study coordinator. All outcome measures were obtained by study staff blinded to the assignment of treatment group.

    Study Participants

    Patients with chronic low back pain (n = 162) were randomly assigned to the following treatment groups (54 patients per group): (1) spinal manipulation, (2) spinal mobilization, or (3) placebo. The Box lists the inclusion and exclusion criteria for the study. In brief, key inclusion criteria were: being 18 to 45 years of age, reporting low back pain constantly or on most days for the last 3 months and low back pain that has caused them to seek care or consultation from a health care practitioner, and average pain of at least 2 on a scale of 0 to 10 (with higher scores indicating greater pain) and a Roland-Morris Disability Questionnaire score of at least 4 (scores range from 0 to 24, with higher values indicating greater disability). To further reduce heterogeneity associated with low back pain, all potential participants completed a physical exam to determine whether they had at least 3 of 4 clinical characteristics that have been associated with positive response to spinal manipulation.19 In the original clinical prediction rule, an individual had to meet 4 of 5 characteristics (ie, symptoms for <16 days, no symptoms distal to the knee, low fear avoidance behavior, at least 1 hypomobile vertebral segment, and at least 1 hip with internal range of motion greater than 35 degrees).19 As this trial sought to examine spinal manipulative therapies in a cohort with chronic back pain, none of the participants had symptom duration of less than 16 days. Interventions allowed during the trial were over-the-counter pain relief medications (eg, ibuprofen, acetaminophen) and application of heat or ice packs. However, narcotics, muscle relaxants, manipulation, mobilization, acupuncture, or massage treatments were prohibited.

    Box Section Ref ID
    Box.

    Inclusion and Exclusion Criteria for Study Participation

    Inclusion
    • Between 18 and 45 years of age

    • Answer yes to the following questions:

      • Have you had low back pain constantly or on most days for the last 3 months?

      • Has your back pain caused you to seek care or consultation from a health care provider?

    • Average pain intensity assessed using the Numerical Pain Rating Scale over the past week ≥2 on a 0-10 numerical pain scale

    • Roland-Morris Disability Questionnaire score ≥4

    • Exhibit at least 3 of the following findings reported in the clinical prediction rules for spinal manipulation:

      • No symptoms distal to the knee

      • Fear Avoidance Beliefs Questionnaire work subscale score <19

      • At least 1 hypomobile lumbar spinal segment

      • At least 1 hip with >35 degrees internal rotation range of motion

    Exclusion
    • Have a personal history of the following neurological disorders: Alzheimer disease, amyotrophic lateral sclerosis, multiple sclerosis, Parkinson disease, or stroke

    • Have a history of the congestive heart failure or heart attack in past 24 months

    • Have a body mass index greater than 35 kg/m2

    • Have used narcotics or muscle relaxants within 30 days prior to study enrollment

    • Have clinical depression (ie, score 24 or higher on the Center for Epidemiology Depression Scale)

    • Report having pending litigation related to an episode of low back pain or are receiving any type of disability services related to low back pain

    • Have active cancer

    • Are blind

    • Report being pregnant, lactating, or that they anticipate becoming pregnant in the next 3 months

    • Current drug or alcohol use or dependence that, in the opinion of the primary investigators, would interfere with adherence to study requirements.

    Participant Recruitment

    We used print and media advertisements, including mass mailing campaigns, to recruit a broad set of individuals with low back pain. This recruitment resulted in 4903 people completing a brief online survey to determine initial eligibility. In general, the vast majority of these potential participants were excluded owing to (1) insufficient pain levels, (2) insufficient duration of symptoms, (3) receiving prohibited interventions, or (4) age outside of the criterion. Individuals who met initial study criteria (n = 182) were then scheduled for an in-person physical screening prior to assignment to a treatment group. Our inclusion and exclusion criteria were designed to optimize the potential for observing an effect of manipulative intervention. Accordingly, a relatively homogenous group of individuals with chronic low back pain who were young and without obesity was enrolled (individuals with above class 1 [low-risk] obesity, defined by a body mass index [calculated as weight in kilograms divided by height in meters squared] of 30 to 34.9, were excluded). We postulate that these criteria minimized the confounding effects of aging and obesity and likely the comorbidities associated with these factors. Careful investigator bias control measures included the following: (1) study personnel conducting the outcome assessments were blind to group assignment throughout the length of the study, (2) clinicians were not aware that the cold laser was a sham intervention, and (3) the statistician and principal investigators remained blind to group assignment until data collection and analyses were completed. While participants could not be blinded to the assigned treatment group, they were unaware that the cold laser was inert (ie, placebo).

    Study Timeline

    Eligible participants were enrolled into the study and randomized to an intervention group, baseline clinical measures were obtained, a treatment intervention was performed, and then the clinical measures were repeated (ie, immediately after the first treatment). Baseline measures to characterize the sample are provided in the Box. Participants then received 5 more treatments over the next 3 weeks. Prior to the second treatment intervention, participant expectations for treatment success were assessed using a credibility and expectancy questionnaire.20 The credibility and expectancy instrument consists of 7 questions with a 9-point Likert scale to assess how confident the participant is that the treatment they have received has the potential to reduce their symptoms. It is often used to assess the strength of the placebo treatment group in randomized trials. Three (±1) days after the final treatment, participants reported back to the laboratory for a follow-up assessment of all clinical measures (ie, primary end point). Participants returned approximately 4 weeks after their last treatment for a follow-up assessment of the clinical outcome measures.

    Study Interventions
    Spinal Manipulation Treatment

    The participant was placed in a side-lying position facing the clinician with the more painful side facing upward. The clinician passively flexed the participant’s hips and knees to induce lumbar spine flexion until they felt the spinous process of the affected lumbar vertebrae begin to move. Next, the clinician passively rotated the participant’s torso opposite to the side they were lying on until they felt rotation in the vertebra above the suspected lesion. The clinician applied a rapid thrust to the shoulder (anterior to posterior force) and pelvis (posterior to anterior force) resulting in a rotation force couple on the hypomobile segment. If a cavitation (ie, an audible pop) occurred, the treatment was considered complete. If no cavitation was produced, the participant was repositioned and the manipulation was attempted again. A maximum of 2 attempts per side was permitted. If no cavitation was produced after the 4 attempts (ie, 2 per side), the treatment was considered complete.

    Spinal Mobilization Treatment

    The participant was positioned using the same technique as described above. The clinician then placed 1 hand on the anterior shoulder and 1 hand on the posterior pelvis. The participant was asked to try to gently push the shoulder and pelvis into the clinician’s hands. Thus, they performed an isometric rotation of the torso resulting in a rotation force couple on the hypomobile segment. The clinician had the participant hold the contraction for a minimum of 7 seconds and a maximum of 60 seconds if the patient could comfortably tolerate the stretch. If a cavitation occurred or the clinician assessed a release in tissue tension, the treatment was considered complete. Otherwise, the clinician repositioned the patient as needed and repeated the treatment for up to 10 minutes.

    Placebo (Sham Laser) Treatment

    The laser manufacturer (MedX Health Corp) provided a MedX 1100 system that did not deliver any significant amount of light energy or heat but otherwise appeared operational to participants and clinicians. The sham laser was delivered over the painful region with the study participant positioned as described for spinal manipulation and spinal mobilization treatments.

    Practitioners, Adherence, and Safety Assessments

    Licensed clinicians (either a doctor of osteopathic medicine or physical therapist), with at least 3 years of clinical experience using manipulative therapies provided all treatments. A yearly workshop organized by the study team harmonized treatment interventions to ensure fidelity to the interventions described above. Successful adherence was defined as a study participant receiving at least 5 of the 6 treatments (83%). At each visit, all negative changes in health status were recorded as adverse events with attribution and grading determined based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events.

    Statistical Analysis

    Sample size calculations for this study have been previously described.18 In brief, based on extant studies of spinal manipulation, we used a Cohen d effect size of 0.5 for simulation studies that indicated 54 subjects per treatment group would be sufficient to achieve power of 0.8 to detect a clinically meaningful treatment effect for coprimary outcomes (ie, change in Numerical Pain Rating Scale [NPRS] score >2 and disability >3) at our primary end point. Sample size calculations also assumed a 10% attrition rate.

    The primary hypotheses were that (1) the spinal manipulation and the spinal mobilization groups would display a significantly larger reduction in NPRS level from baseline than the placebo at the primary end point and (2) the spinal manipulation and the spinal mobilization groups would display a significantly larger reduction in Roland-Morris Disability Questionnaire score than the placebo at the primary end point. One-tailed tests were used to assess these directional hypotheses. A 2-point reduction in NPRS score21 and a 3-point reduction in Roland-Morris Disability Questionnaire score22 were considered clinically meaningful important differences. P < .05 was used to indicate statistical significance.

    Data were examined to check for the following key assumptions: (1) normal distribution of random intercepts and slopes as well as residuals and (2) homogeneity of residual variances across the 3 treatment groups. Linear mixed-effects regression analyses served as the main analytic framework. This regression technique incorporates miscellaneous factors (eg, blocks and practitioners) as random effects so that the variances due to those factors can be partitioned. Furthermore, the maximum-likelihood estimation allows participants with missing data to be included in the model if the observations were missing completely at random or missing at random.

    All regression models incorporated random intercept terms to accommodate the within-subject variance associated with longitudinal experimental designs and fixed-factor parameters for the main effects of group (sham-laser control as reference), main effect for time (baseline as reference), and the simple interaction terms of group by time (relative to control and baseline). Biological sex was included in each of the models. Additional a priori contrasts comparing changes from baseline between the 2 intervention groups (ie, simple interaction contrasts) were also performed, with Holm alpha adjustments to preserve the familywise error rates to 0.05.

    Intention-to-Treat Analysis

    All randomized study participants with at least a baseline assessment were included in the intention-to-treat (ITT) analysis. This trial enrolled and randomized participants following an in-person physical examination. Baseline measures were then completed in a follow-up visit within 7 days of the physical screening. Four of the randomized participants dropped out before baseline measures. Accordingly, our primary analysis does not meet the strict definition for ITT analysis. Thus, we used a near ITT analysis as the primary method for assessing outcomes, and maximum-likelihood estimation was used to estimate any missing observations.

    Per-Protocol Analysis

    For the per-protocol analysis (PPA), we excluded study participants who (1) attended fewer than 5 treatment sessions and (2) received prohibited concomitant interventions or (3) developed an exclusionary medical condition while on the study protocol. The outcomes from the ITT analysis and PPA were nearly identical (ie, differences in estimated marginal means were generally less than 0.5, with no differences in significance). Accordingly, only the results of the ITT analysis are presented.

    Results

    A total of 162 participants (92 women [57%] and 70 men [43%]) with a mean (SD) age of 25.0 (6.2) years (range, 18.6-45.9 years) were enrolled in this trial. At baseline, this cohort reported a mean (SD) pain score over the last 7 days of 4.3 (2.5) on the NPRS (range, 0-10), a mean (SD) score of 9.9 (4.5) on the Roland-Morris Disability Questionnaire (range, 0-24), and mean (SD) length of chronic pain of 6.2 (5.1) years, indicating mild to moderate back pain of long duration. Fifty-four participants were randomized to the spinal manipulation group (31 women [57%] and 23 men [43%]), 54 participants to the spinal mobilization group (31 women [57%] and 23 men [43%]), and 54 participants to the placebo group (30 women [56%] and 24 men [44%]). Four participants were withdrawn from the study after the randomization process owing to scheduling issues (2 from the spinal manipulation group, 1 from spinal mobilization, and 1 from placebo) and never completed baseline measures or any part of the treatments and follow-up assessments. An additional 5 individuals did not complete the allocated intervention and follow-up visits. Participant characteristics as a function of treatment group are reported in Table 1.

    Primary Outcomes

    At the primary end point, there was no significant difference in the change in pain scores between spinal manipulation and spinal mobilization (0.24; 95% CI, −0.38 to 0.86; P = .45), spinal manipulation and placebo (−0.03; 95% CI, −0.65 to 0.59; P = .92), or spinal mobilization and placebo (−0.26; 95% CI, −0.38 to 0.85; P = .39) (Figure 2A). There was no significant difference in change in self-reported disability scores between spinal manipulation and spinal mobilization (−1.00; 95% CI, −2.37 to 0.36; P = .14), spinal manipulation and placebo (−0.07; 95% CI, −1.43 to 1.29; P = .92), or spinal mobilization and placebo (0.93; 95% CI, −0.41 to 2.29; P = .17) (Figure 2B). There was no significant interaction of sex on pain or disability measures.

    Treatment Expectancy

    A comparison of treatment credibility and expectancy ratings across groups was not statistically significant (F2,151 = 1.70, P = .19), indicating that, on average, participants in each group had similar expectations regarding the likely benefit of their assigned treatment. Next, we examined the relationship between these individual treatment expectancy ratings (Table 2), obtained before the second treatment session, and changes in current NPRS ratings (ie, 72 hours posttreatment − baseline). For the sample as a whole, treatment expectancy scores were inversely correlated with the change in pain ratings (r = −0.396; P < .01), indicating that those who had higher expectations of treatment success reported larger decreases in pain with treatment. When these expectancy effects were examined within each treatment group, significant inverse correlations were observed for placebo (r = −0.569; P < .001) and spinal manipulation (r = −0.423; P = .002) but not spinal mobilization (r = −0.188; P = .18). The changes in Roland-Morris Disability Questionnaire ratings (ie, session 9 − session 2) were not significantly related to treatment expectancy.

    Discussion

    The RELIEF Study is one of the few randomized clinical trials to date to compare the effectiveness of 2 common manipulative therapy techniques to a robust placebo for treatment of chronic low back pain. We found no effects of treatment group on the change in pain and disability immediately following a 3-week course of treatment or at the follow-up 4 weeks after treatment completion. Although we hypothesized that spinal manipulation and spinal mobilization would be more effective in reducing pain and disability compared with the placebo (ie, sham cold laser), this hypothesis was not supported by the data.

    The clinical effectiveness of manipulative therapy techniques for acute and subacute low back pain has been reported6-8; however, the evidence on the effectiveness for reducing pain in chronic low back pain sufferers is mixed.9-11 We developed a modified version of a clinical prediction rule to identify individuals with chronic low back pain most likely to respond to a manipulative therapy intervention. Specifically, we modified the clinical prediction rule by Childs and colleagues19 by removing 1 of the 5 criteria (ie, symptoms <16 days) for this study. It should be noted that there were no data to indicate that acuteness of symptom onset was more heavily weighted than the 4 other criteria (ie, no symptoms distal to the knee, low fear avoidance behavior, at least 1 hypomobile vertebral segment, and at least 1 hip with internal range of motion greater than 35 degrees). Even with a modified clinical prediction rule to identify a cohort of individuals with chronic back pain most likely to respond to manipulative therapies, our data indicate that spinal manipulation and spinal mobilization were not very effective in reducing pain and disability in this cohort. This finding is consistent with those of Dougherty and colleagues,23 who also found that a modified version of this rule was not effective in discriminating which patients with chronic low back pain are most likely to respond to spinal manipulation. It is important to note that findings were reported by Dougherty and colleagues more than a year after subject recruitment began for the RELIEF Study.

    There is also the possibility that manipulative therapy techniques are not as effective for treating mild to moderate pain conditions. Across treatment groups, participants in this study reported a mean pain score of 4.2 (on a 0-10 scale) when asked to rate their pain over the last 7 days. While our data show that manipulative therapy techniques were no more effective than an effective placebo treatment for mild to moderate chronic low back pain, it is possible that these techniques would be more effective for individuals with more severe pain. Alternatively, the finding that manipulative therapies were not very effective in a young cohort of patients with mild to moderate low back pain with few confounding factors may provide additional evidence that this approach is not ideal for chronic back pain. That possibility would be consistent with the literature that indicates manipulation is a reasonable, effective intervention for those with acute low back pain6 whereas the results are more mixed in chronic low back pain.9-11 Although the young age cohort in our study, which likely arose from our primary recruitment strategy being direct emails and online advertisements, is a limitation with respect to generalizability, a recent paper by Manogharan and colleagues24 suggests there are relatively small differences in baseline characteristics and prognosis among young, middle-aged, and older cohorts of patients with low back pain. In sum, these findings provide additional evidence about the limits of manipulative therapies in chronic low back pain.

    Another consideration, not only in the RELIEF trial but in all studies on manipulative therapy, is the effectiveness of the placebo to create a true control condition. Whereas an effective placebo is critical to maintain blinding and reduce the risk of bias, poor placebos are quite common in low back pain studies.25 A review of low back pain trials by Machado and colleagues25 reported that 20% of trials had a placebo that was a potentially genuine treatment, 13% maintained adequacy of blinding, and most that assessed treatment expectations found that participants had lower expectations of placebo as compared to the active treatment groups.25 Another review reported that the quality of placebos typically used in studies on manipulative therapy is inadequate and that few studies controlled for or assessed treatment expectations.26 We used a validated treatment expectancy measure,20 and, consistent with Puhl et al,26 our data clearly showed that expectancy of treatment success was related to reductions in pain but not disability. Although there was no effect of treatment group on participant treatment expectancy ratings, the sham cold laser treatment group showed the strongest relationship between expectancy and pain reduction. Taken in total, these data suggest that sham cold laser is an effective placebo for spinal manipulation studies and that the power of participant expectations can be quite large. These findings reinforce the conclusions from Puhl et al26 that future trials should carefully select the control treatment, and the effectiveness of the control must be evaluated to provide confidence for assessing the effectiveness of manipulative therapy.

    Limitations

    This study has limitations that should be noted. First, our participants were relatively young adults with only mild to moderate chronic low back pain with low levels of self-reported disability. Although this age cohort may not seek medical care for low back pain as often as middle-aged and older adults, it is worth noting the average duration of symptoms for this cohort was greater than 6 years. Thus, this is potentially an understudied cohort, and data on treatment effectiveness of manual therapies is needed. Second, the trial used a single-blinded design. However, this design is consistent with all studies of spinal manual therapies, as it is impossible to have a true double-blind design because the clinician will obviously know what treatment they are providing. We attempted to minimize any bias by having the data collection team assessing clinical outcomes blinded to treatment assignment. Another potential limitation is that the interventions were restricted to the isolated application of manipulation, mobilization, or placebo (ie, inert cold laser) using a classic randomized trial design. This approach was designed to reduce potential confounds by the application of concomitant interventions, such as stretching and strengthening exercises. Thus, a future study that uses a pragmatic clinical trial design approach could provide further understanding of the potential additive benefits of these manual therapies.

    Conclusions

    Our findings indicated that spinal manipulation and spinal mobilization were no more effective than a well-chosen placebo in reducing pain and disability in patients with chronic low back pain. We conclude that these manipulative therapy techniques do not appear to be effective for chronic low back pain, at least among relatively young individuals with mild to moderate back pain.

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    Article Information

    Accepted for Publication: May 22, 2020.

    Published: August 5, 2020. doi:10.1001/jamanetworkopen.2020.12589

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Thomas JS et al. JAMA Network Open.

    Corresponding Authors: James S. Thomas, PT, PhD, Department of Physical Therapy, Virginia Commonwealth University, 900 E Leigh St, Room 4208, Richmond, VA 23298 (jthomas32@vcu.edu); Brian Clark, PhD, OMNI, Department of Biomedical Sciences, Ohio University, Athens, OH 45701 (clarkb2@ohio.edu).

    Author Contributions: Drs Thomas and Clark had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Thomas, Clark, Russ, France, Corcos.

    Acquisition, analysis, or interpretation of data: Thomas, Clark, Russ, France, Ploutz-Snyder.

    Drafting of the manuscript: Thomas, Russ, France, Ploutz-Snyder.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Thomas, France, Ploutz-Snyder.

    Obtained funding: Thomas, Clark, France.

    Administrative, technical, or material support: Thomas, Clark, France, Corcos.

    Supervision: Thomas, Clark.

    Conflict of Interest Disclosures: Dr Thomas reported receiving grants from the National Institutes of Health (NIH) during the conduct of this study. Dr Clark reported receiving grants from the NIH during the conduct of the study and grants from the Osteopathic Heritage Foundations and the American Osteopathic Association outside the submitted work. Dr Russ reported receiving grants from the NIH during the conduct of the study. Dr France reported receiving grants from the NIH during the conduct of the study. Dr Ploutz-Snyder reported receiving grants from the NIH, the Department of Justice, NASA, the Merk Foundation, and the Ethel and James Flinn Foundation for effort as a biostatistician during the conduct of the study. No other disclosures were reported.

    Funding/Support: Research reported in this publication was supported by the National Center for Complementary and Integrative Health of the NIH under award number R01AT006978 (Drs Thomas and Clark).

    Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    RELIEF Study Investigators: Study coordinator: Rebecca Batey, MFA (School of Rehabilitation and Communication Sciences, Athens, Ohio); treatment providers: Timothy Law, DO, and Simeon Hain, DO (Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio); James Odenthal, DPT, and Betty Sindelar, PhD, PT (School of Rehabilitation and Communication Sciences, Athens, Ohio); trainees and postdoctoral fellows: Sam Leikham, PhD, and Megan Applegate, PhD (School of Rehabilitation and Communication Sciences, Athens, Ohio) and Niladri Mahato, PhD (Department of Biomedical Sciences, Ohio University, Athens, Ohio).

    Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

    Data Sharing Statement: See Supplement 2.

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