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Original Investigation
December 25, 2013

Effect of Nortriptyline on Symptoms of Idiopathic Gastroparesis: The NORIG Randomized Clinical Trial

Author Affiliations
  • 1Temple University, Philadelphia, Pennsylvania
  • 2Johns Hopkins University, Baltimore, Maryland
  • 3University of Louisville, Louisville, Kentucky
  • 4Texas Tech University, El Paso
  • 5Stanford University, Palo Alto, California
  • 6California Pacific Medical Center, San Francisco
  • 7Wake Forest University, Winston-Salem, North Carolina
  • 8University of Michigan, Ann Arbor
  • 9Mayo Clinic, Rochester, Minnesota
  • 10National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland
  • 11The Johns Hopkins Hospital, Baltimore, Maryland
JAMA. 2013;310(24):2640-2649. doi:10.1001/jama.2013.282833
Abstract

Importance  Gastroparesis remains a challenging syndrome to manage, with few effective treatments and a lack of rigorously controlled trials. Tricyclic antidepressants are often used to treat refractory symptoms of nausea, vomiting, and abdominal pain. Evidence from well-designed studies for this use is lacking.

Objective  To determine whether treatment with nortriptyline results in symptomatic improvement in patients with idiopathic gastroparesis.

Design, Setting, and Participants  The NORIG (Nortriptyline for Idiopathic Gastroparesis) trial, a 15-week multicenter, parallel-group, placebo-controlled, double-masked, randomized clinical trial from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC), comparing nortriptyline with placebo for symptomatic relief in idiopathic gastroparesis. One hundred thirty patients with idiopathic gastroparesis were enrolled between March 2009 and June 2012 at 7 US academic medical centers. Patient follow-up was completed in October 2012. Inclusion criteria included delayed gastric emptying and moderate to severe symptom scores using the Gastroparesis Cardinal Symptom Index (GCSI).

Interventions  Nortriptyline vs placebo. Study drug dose was increased at 3-week intervals (10, 25, 50, 75 mg) up to 75 mg at 12 weeks.

Main Outcomes and Measures  The primary outcome measure of symptomatic improvement was a decrease from the patient’s baseline GCSI score of at least 50% on 2 consecutive 3-week GCSI assessments during 15 weeks of treatment.

Results  The primary symptomatic improvement outcome did not differ between 65 patients randomized to nortriptyline vs 65 patients randomized to placebo: 15 (23% [95% CI, 14%-35%]) in the nortriptyline group vs 14 (21% [95% CI, 12%-34%]) in the placebo group (P = .86). Treatment was stopped more often in the nortriptyline group (19 [29% {95% CI, 19%-42%}]) than in the placebo group (6 [9%] {95% CI, 3%-19%}]) (P = .007), but numbers of adverse events were not different (27 [95% CI, 18-39] vs 28 [95% CI, 19-40]) (P = .89).

Conclusions and Relevance  Among patients with idiopathic gastroparesis, the use of nortriptyline compared with placebo for 15 weeks did not result in improvement in overall symptoms. These findings do not support the use of nortriptyline for idiopathic gastroparesis.

Trial Registration  clinicaltrials.gov Identifier: NCT00765895

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