Nortriptyline for Idiopathic Gastroparesis (NORIG)

Nortriptyline for Idiopathic Gastroparesis: A Multicenter, Randomized, Double-Masked, Placebo-Controlled Trial (NORIG)

The principal objective of this multicenter, randomized, placebo-controlled trial is to evaluate whether treatment with nortriptyline will improve gastroparesis symptoms compared with placebo.

Study Overview

• Status: Completed
• Conditions: Idiopathic Gastroparesis
• Intervention / Treatment: Drug: Nortriptyline Hydrochloride; Drug: Placebo (for nortriptyline)

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
    • Stanford, California, United States, 94305-5187
      • Stanford University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • Texas
    • El Paso, Texas, United States, 79905
      • Texas Tech University Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 21 through 65 years old at registration
• Documentation of delayed gastric emptying on gastric emptying scintigraphy within 2 years of registration, defined as greater than 60% retention at 2 hours or greater than 10% retention at 4 hours
• Symptoms of gastroparesis for at least 6 months (does not have to be contiguous) prior to registration with Gastroparesis Cardinal Symptom Index (GCSI) score of 21 or greater
• Negative upper endoscopy or upper GI series within 2 years of registration

Exclusion Criteria:

• Normal gastric emptying confirmed with scintigraphy
• Diabetic gastroparesis or post-surgical gastroparesis including fundoplication
• Another active disorder which could explain symptoms in the opinion of the investigator
• History of significant cardiac arrhythmias and/or prolonged QTc
• History of seizures
• Use of narcotics more than 3 days per week
• Use of tricyclic antidepressants for refractory symptoms of gastroparesis within 6 weeks prior to randomization
• Use of strongly anticholinergic medications
• Use of calcium channel blockers
• Use of erythromycin
• Clear history of failed trial of nortriptyline use for gastroparetic symptoms
• Symptoms of primary depression or suicidal ideation

• Contraindications to nortriptyline:

  1. hypersensitivity or allergy to any tricyclic antidepressant drug
  2. concomitant therapy with a monoamine oxidase inhibitor (MAOI)
  3. recent myocardial infarction
  4. glaucoma
• Pregnancy or nursing
• Any other condition, which in the opinion of the investigator would impede compliance or hinder completion of the study
• Use of a G tube, J tube,or a central catheter for nutrition
• Use of a gastric electrical stimulator
• Failure to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nortriptyline; Nortriptyline Hydrochloride dose escalation from 10 mg to 75 mg	Drug: Nortriptyline Hydrochloride; Nortriptyline; 10 mg, one capsule, po qhs (by mouth at bedtime each night) x 3 weeks, f03 visit, 25 mg, one capsule, po qhs x 3 weeks, f06 visit, 50 mg, two capsules, po qhs x 3 weeks, f09 visit, 75 mg, three capsules, po qhs x 6 weeks, f15 visit: taper study drug by one capsule a week, off study drug for the last week; Other Names: Pamelor; Nortriptyline HCl
Placebo Comparator: Placebo (for nortriptyline); No treatment	Drug: Placebo (for nortriptyline); Placebo (for nortriptyline), 10 mg, one capsule, po qhs x 3 weeks, f03 visit, 25 mg, one capsule, po qhs x 3 weeks;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease From the Baseline GCSI of at Least 50% on Any Two Consecutive Follow-up Visits	A decrease from the baseline Gastroparesis Cardinal Symptom Index (GCSI) score (sum of the 9 individual symptom scores) of at least 50% on any two consecutive follow-up visits during the 15 week treatment period with maximum tolerated study drug dose. The total score ranges from 0-45 with higher scores indicating greater symptom severity.	at end of treatment, 15 weeks from baseline assessment

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

General Publications

• Parkman HP, Van Natta ML, Abell TL, McCallum RW, Sarosiek I, Nguyen L, Snape WJ, Koch KL, Hasler WL, Farrugia G, Lee L, Unalp-Arida A, Tonascia J, Hamilton F, Pasricha PJ. Effect of nortriptyline on symptoms of idiopathic gastroparesis: the NORIG randomized clinical trial. JAMA. 2013 Dec 25;310(24):2640-9. doi: 10.1001/jama.2013.282833.

Helpful Links

• Click here for information on gastroparesis research

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2009
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: October 2, 2008
• First Submitted That Met QC Criteria: October 2, 2008
• First Posted (Estimate): October 3, 2008

Study Record Updates

• Last Update Posted (Actual): May 14, 2020
• Last Update Submitted That Met QC Criteria: April 30, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: idiopathic gastroparesis
• Additional Relevant MeSH Terms: Digestive System Diseases; Neurologic Manifestations; Gastrointestinal Diseases; Stomach Diseases; Paralysis; Gastroparesis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Tricyclic; Adrenergic Uptake Inhibitors; Nortriptyline
• Other Study ID Numbers: U01DK074008 NORIG; 1U01DK073983 (U.S. NIH Grant/Contract); 1U01DK073975 (U.S. NIH Grant/Contract); 1U01DK073985 (U.S. NIH Grant/Contract); 1U01DK074007 (U.S. NIH Grant/Contract); 1U01DK073974 (U.S. NIH Grant/Contract); 1U01DK074008 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/norig/?query=norig

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No