Effect of nortriptyline on symptoms of idiopathic gastroparesis: The NORIG randomized clinical trial

Henry P. Parkman, Mark L Van Natta, Thomas L. Abell, Richard W. McCallum, Irene Sarosiek, Linda Nguyen, William J. Snape, Kenneth L. Koch, William L. Hasler, Gianrico Farrugia, Linda A Lee, Aynur Unalp-Arida, James A Tonascia, Frank Hamilton, Pankaj Jay Pasricha

Research output: Contribution to journalArticle

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

Original languageEnglish (US)
Pages (from-to)2640-2649
Number of pages10
JournalJournal of the American Medical Association
Volume310
Issue number24
DOIs
StatePublished - 2013

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Gastroparesis
Nortriptyline
Randomized Controlled Trials
Placebos
National Institute of Diabetes and Digestive and Kidney Diseases (U.S.)
Symptom Assessment
Tricyclic Antidepressive Agents
Gastric Emptying
Therapeutics
Nausea
Abdominal Pain
Vomiting

ASJC Scopus subject areas

  • Medicine(all)

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Effect of nortriptyline on symptoms of idiopathic gastroparesis : The NORIG randomized clinical trial. / Parkman, Henry P.; Van Natta, Mark L; Abell, Thomas L.; McCallum, Richard W.; Sarosiek, Irene; Nguyen, Linda; Snape, William J.; Koch, Kenneth L.; Hasler, William L.; Farrugia, Gianrico; Lee, Linda A; Unalp-Arida, Aynur; Tonascia, James A; Hamilton, Frank; Pasricha, Pankaj Jay.

In: Journal of the American Medical Association, Vol. 310, No. 24, 2013, p. 2640-2649.

Research output: Contribution to journalArticle

Parkman, HP, Van Natta, ML, Abell, TL, McCallum, RW, Sarosiek, I, Nguyen, L, Snape, WJ, Koch, KL, Hasler, WL, Farrugia, G, Lee, LA, Unalp-Arida, A, Tonascia, JA, Hamilton, F & Pasricha, PJ 2013, 'Effect of nortriptyline on symptoms of idiopathic gastroparesis: The NORIG randomized clinical trial', Journal of the American Medical Association, vol. 310, no. 24, pp. 2640-2649. https://doi.org/10.1001/jama.2013.282833
Parkman, Henry P. ; Van Natta, Mark L ; Abell, Thomas L. ; McCallum, Richard W. ; Sarosiek, Irene ; Nguyen, Linda ; Snape, William J. ; Koch, Kenneth L. ; Hasler, William L. ; Farrugia, Gianrico ; Lee, Linda A ; Unalp-Arida, Aynur ; Tonascia, James A ; Hamilton, Frank ; Pasricha, Pankaj Jay. / Effect of nortriptyline on symptoms of idiopathic gastroparesis : The NORIG randomized clinical trial. In: Journal of the American Medical Association. 2013 ; Vol. 310, No. 24. pp. 2640-2649.
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T1 - Effect of nortriptyline on symptoms of idiopathic gastroparesis

T2 - The NORIG randomized clinical trial

AU - Parkman, Henry P.

AU - Van Natta, Mark L

AU - Abell, Thomas L.

AU - McCallum, Richard W.

AU - Sarosiek, Irene

AU - Nguyen, Linda

AU - Snape, William J.

AU - Koch, Kenneth L.

AU - Hasler, William L.

AU - Farrugia, Gianrico

AU - Lee, Linda A

AU - Unalp-Arida, Aynur

AU - Tonascia, James A

AU - Hamilton, Frank

AU - Pasricha, Pankaj Jay

PY - 2013

Y1 - 2013

N2 - 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

AB - 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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