Measuring Disease Progression in Early Parkinson Disease: The National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) Experience | Lifestyle Behaviors | JAMA Neurology | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Suchowersky  O, Reich  S, Perlmutter  J, Zesiewicz  T, Gronseth  G, Weiner  WJ; Quality Standards Subcommittee of the American Academy of Neurology.  Practice parameter: diagnosis and prognosis of new onset Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.  Neurology. 2006;66(7):968-975.PubMedGoogle ScholarCrossref
Parashos  SA, Maraganore  DM, O’Brien  PC, Rocca  WA.  Medical services utilization and prognosis in Parkinson disease: a population-based study.  Mayo Clin Proc. 2002;77(9):918-925.PubMedGoogle ScholarCrossref
Elm  JJ, Goetz  CG, Ravina  B,  et al; NET-PD Investigators.  A responsive outcome for Parkinson’s disease neuroprotection futility studies.  Ann Neurol. 2005;57(2):197-203.PubMedGoogle ScholarCrossref
NINDS NET-PD Investigators.  A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease.  Neurology. 2006;66(5):664-671.PubMedGoogle ScholarCrossref
NINDS NET-PD Investigators.  A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease.  Neurology. 2007;68(1):20-28.PubMedGoogle ScholarCrossref
Parashos  SA, Swearingen  CJ, Biglan  KM,  et al; NET-PD Investigators.  Determinants of the timing of symptomatic treatment in early Parkinson disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) Experience.  Arch Neurol. 2009;66(9):1099-1104.PubMedGoogle ScholarCrossref
Fahn  S, Elton  RL; Members of the UPDRS Development Committee. Unified Parkinson's Disease Rating Scale. In: Fahn  S, Marsden  CO, Calne  DB, Goldstein  M, eds.  Recent Developments in Parkinson's Disease. Florham Park, NJ: Macmillan Health Care Information; 1987:153-164.
van Swieten  JC, Koudstaal  PJ, Visser  MC, Schouten  HJ, van Gijn  J.  Interobserver agreement for the assessment of handicap in stroke patients.  Stroke. 1988;19(5):604-607.PubMedGoogle ScholarCrossref
Schwab  RS, England  ACJ. Projection technique for evaluating surgery in Parkinson's disease. In: Gillingham  FJ, Donaldson  IML, eds.  Third Symposium on Parkinson's Disease, held at the Royal College of Surgeons of Edinburgh on 20, 21 and 22 May 1968. Edinburgh, Scotland: E & S Livingstone; 1969:152-157.
Shoulson  I, Kurlan  R, Rubin  A,  et al. Assessment of functional capacity in neurodegenerative disorders: Huntington’s disease as a prototype. In: Munsat  TL, ed.  Quantification of Neurologic Deficit. Waltham, MA: Butterworth-Heinemann; 1989:285-309.
Jenkinson  C, Fitzpatrick  R, Peto  V, Greenhall  R, Hyman  N.  The Parkinson’s Disease Questionnaire (PDQ-39): development and validation of a Parkinson’s disease summary index score.  Age Ageing. 1997;26(5):353-357.PubMedGoogle ScholarCrossref
Ware  JE  Jr, Kosinski  M, Turner-Bowker  DM, Gandek  B.  How to Score Version 2 of the SF-12 Health Survey (With a Supplement Documenting Version 1). Lincoln, RI: QualityMetric Inc; 2002.
The Parkinson Study Group.  Effect of deprenyl on the progression of disability in early Parkinson’s disease.  N Engl J Med. 1989;321(20):1364-1371.PubMedGoogle ScholarCrossref
Dafni  UG, Tsiatis  AA.  Evaluating surrogate markers of clinical outcome when measured with error.  Biometrics. 1998;54(4):1445-1462.PubMedGoogle ScholarCrossref
Hosmer  DW, Lemeshow  S.  Applied Logistic Regression. New York, NY: Wiley; 1989.
Grambsch  P, Therneau  TM.  Proportional hazards tests and diagnostics based on weighted residuals.  Biometrika. 1994;81(3):515-526. doi:10.1093/biomet/81.3.515.Google ScholarCrossref
McDermott  MP, Jankovic  J, Carter  J,  et al; The Parkinson Study Group.  Factors predictive of the need for levodopa therapy in early, untreated Parkinson’s disease.  Arch Neurol. 1995;52(6):565-570.PubMedGoogle ScholarCrossref
Marras  C, McDermott  MP, Marek  K,  et al; Parkinson Study Group DATATOP and PRECEPT investigators.  Predictors of time to requiring dopaminergic treatment in 2 Parkinson’s disease cohorts.  Mov Disord. 2011;26(4):608-613.PubMedGoogle ScholarCrossref
Shulman  LM, Gruber-Baldini  AL, Anderson  KE,  et al.  The evolution of disability in Parkinson disease.  Mov Disord. 2008;23(6):790-796.PubMedGoogle ScholarCrossref
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    1 Comment for this article
    Possible reasons for the unsatisfactory results of Ubiquinone trials on patients with early Parkinson .
    Ahmed Negida | Zagazig University , Faculty of Medicine , Egypt
    Results of clinical trials on coenzyme Q10 for early Parkinson aren't satisfactory to the expected extent (1). However this doesn't mean that coenzyme Q10 has no effect on neurons protection .It's still possible that Coenzyme Q10 can slow the progress of Parkinson in earlier cases that don't require medications . Another possible reason for this negative results is that Vitamin E reduces the absorption of coenzyme Q10 (2) . Also Ubiquinone mayn't give the expected outcome due to its hydrophobicity and large molecular weight which makes the absorption of dietary CoQ10 is slow and very limited(3). A recent study showed that the water soluble form Ubisol-Q10 is effective in low doses (4).References :-1. Shults CW. Treatments of Parkinson disease: circa 2003. Arch Neurol. 2003;60:1680-1684. doi:10.1001/archneur.60.12.1680.2. Lass A, Sohal RS. Effect of coenzyme Q(10) and alpha-tocopherol content of mitochondria on the production of superoxide anion radicals. FASEB J. 2000;14(1):87-94. Available at: Bhagavan HN, Chopra RK. Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006;40(5):445-53. doi:10.1080/10715760600617843.4. Muthukumaran K, Leahy S, Harrison K, et al. Orally delivered water soluble Coenzyme Q10 (Ubisol-Q10) blocks on-going neurodegeneration in rats exposed to paraquat: potential for therapeutic application in Parkinson’s disease. BMC Neurosci. 2014;15(1):21. doi:10.1186/1471-2202-15-21.
    Original Investigation
    June 2014

    Measuring Disease Progression in Early Parkinson Disease: The National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) Experience

    Author Affiliations
    • 1Struthers Parkinson’s Center, Golden Valley, Minnesota
    • 2Division of Biostatistics, University of Texas at Houston
    • 3Department of Neurology, University of Rochester, Rochester, New York
    • 4State University of New York, Downstate Medical Center, Brooklyn
    • 5The Parkinson’s Institute and Clinical Center, Sunnyvale, California
    • 6VA Pacific Islands Health Care System, Honolulu, Hawaii
    • 7Department of Neurology, University of Maryland School of Medicine, Baltimore
    JAMA Neurol. 2014;71(6):710-716. doi:10.1001/jamaneurol.2014.391

    Importance  Optimizing assessments of rate of progression in Parkinson disease (PD) is important in designing clinical trials, especially of potential disease-modifying agents.

    Objective  To examine the value of measures of impairment, disability, and quality of life in assessing progression in early PD.

    Design, Setting, and Participants  Inception cohort analysis of data from 413 patients with early, untreated PD who were enrolled in 2 multicenter, randomized, double-blind clinical trials.

    Interventions  Participants were randomly assigned to 1 of 5 treatments (67 received creatine, 66 received minocycline, 71 received coenzyme Q10, 71 received GPI-1485, and 138 received placebo). We assessed the association between the rates of change in measures of impairment, disability, and quality of life and time to initiation of symptomatic treatment.

    Main Outcomes and Measures  Time between baseline assessment and need for the initiation of symptomatic pharmaceutical treatment for PD was the primary indicator of disease progression.

    Results  After adjusting for baseline confounding variables with regard to the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II score, the UPDRS Part III score, the modified Rankin Scale score, level of education, and treatment group, we assessed the rate of change for the following measurements: the UPDRS Part II score; the UPDRS Part III score; the Schwab and England Independence Scale score (which measures activities of daily living); the Total Functional Capacity scale; the 39-item Parkinson’s Disease Questionnaire, summary index, and activities of daily living subscale; and version 2 of the 12-item Short Form Health Survey Physical Summary and Mental Summary. Variables reaching the statistical threshold in univariate analysis were entered into a multivariable Cox proportional hazards model using time to symptomatic treatment as the dependent variable. More rapid change (ie, worsening) in the UPDRS Part II score (hazard ratio, 1.15 [95% CI, 1.08-1.22] for 1 scale unit change per 6 months), the UPDRS Part III score (hazard ratio, 1.09 [95% CI, 1.06-1.13] for 1 scale unit change per 6 months), and the Schwab and England Independence Scale score (hazard ratio, 1.29 [95% CI, 1.12-1.48] for 5 percentage point change per 6 months) was associated with earlier need for symptomatic therapy.

    Conclusions and Relevance  In early PD, the UPDRS Part II score and Part III score and the Schwab and England Independence Scale score can be used to measure disease progression, whereas the 39-item Parkinson’s Disease Questionnaire and summary index, Total Functional Capacity scale, and the 12-item Short Form Health Survey Physical Summary and Mental Summary are not sensitive to change.

    Trial Registration Identifiers: NCT00063193 and NCT00076492