title: Effect of nortriptyline on symptoms of idiopathic gastroparesis: the NORIG randomized clinical trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00765895.
authors.affiliation: Temple University, Philadelphia, Pennsylvania.
authors.forename: Henry P
authors.initials: HP
authors.lastname: Parkman
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Van Natta
authors.affiliation: University of Louisville, Louisville, Kentucky.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Abell
authors.affiliation: Texas Tech University, El Paso.
authors.forename: Richard W
authors.initials: RW
authors.lastname: McCallum
authors.affiliation: Texas Tech University, El Paso.
authors.forename: Irene
authors.initials: I
authors.lastname: Sarosiek
authors.affiliation: Stanford University, Palo Alto, California.
authors.forename: Linda
authors.initials: L
authors.lastname: Nguyen
authors.affiliation: California Pacific Medical Center, San Francisco.
authors.forename: William J
authors.initials: WJ
authors.lastname: Snape
authors.affiliation: Wake Forest University, Winston-Salem, North Carolina.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Koch
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: William L
authors.initials: WL
authors.lastname: Hasler
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Gianrico
authors.initials: G
authors.lastname: Farrugia
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Linda
authors.initials: L
authors.lastname: Lee
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Aynur
authors.initials: A
authors.lastname: Unalp-Arida
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: James
authors.initials: J
authors.lastname: Tonascia
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.
authors.forename: Frank
authors.initials: F
authors.lastname: Hamilton
authors.affiliation: The Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Pankaj J
authors.initials: PJ
authors.lastname: Pasricha
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D018589:Gastroparesis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D009661:Nortriptyline / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018759:Adrenergic Uptake Inhibitors; D009661:Nortriptyline