Amitriptyline for IBS-like Symptoms in Quiescent Crohn's Disease

NCT07556718 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: HUM00265477
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Many individuals with Crohn's disease continue to experience abdominal pain, bloating, or bowel habit changes even when their inflammation is controlled. Amitriptyline is a medication commonly used at low doses to treat irritable bowel syndrome (IBS) and abdominal pain. This study will assess whether amitriptyline is safe and reduces those ongoing GI symptoms in adults with Crohn's disease in remission.

Conditions

Quiescent Crohn's Disease (CD)

Keywords

Tricyclic antidepressants

Outcome Measures

Primary Outcomes (1)

• Safety reported as the proportion of participants experiencing a serious adverse event (SAE),

  An SAE is defined as an adverse events resulting in hospitalization or emergency department visit and/or suicidal ideation or hallucinations that are considered "probably" or "definitely" related to the study-drug.

  Week 24

Secondary Outcomes (2)

• Efficacy in Abdominal Pain

  Week 24

• Global Symptom Improvement

  Week 24

Study Arms (2)

Amitriptyline

EXPERIMENTAL

Roughly 50 participants

Drug: Amitriptyline

Placebo

PLACEBO COMPARATOR

Roughly 50 participants

Drug: Placebo

Interventions

Amitriptyline DRUG

Amitriptyline will be administered orally once daily. It will be dispensed in capsules or tablets that are visually identical to placebo. Self-titration schedule beginning at 10 mg and increasing to a maximum of 50 mg over the first six weeks, as tolerated. Participants will continue their maximum tolerated dose through Week 24.

Amitriptyline

Placebo DRUG

Placebo capsules or tablets will be visually indistinguishable from amitriptyline to maintain participant and investigator blinding. Self-titration schedule beginning at 10 mg and increasing to a maximum of 50 mg over the first six weeks, as tolerated. Participants will continue their maximum tolerated placebo dose through Week 24.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65 years, inclusive, at the time of consent.
• Established diagnosis of Crohn's disease, confirmed by standard clinical, endoscopic, histologic, and/or radiologic criteria.
• Quiescent Crohn's disease (qCD) defined by provider global assessment of remission for the last 3 months along with at least one of the following within the past 30 days:
• Biochemical remission defined by fecal calprotectin \< 150 mcg/g, OR
• Endoscopic remission defined by colonoscopy demonstrating Simple Endoscopic Scoring (SES)- Crohn's disease (CD) \< 4 per involved segment with no large ulcers (≥5 mm), and Rutgeerts score ≤ i1 (when applicable). OR
• Radiographic evidence of quiescent disease consistent with the protocol.
• Completion of a 12-lead electrocardiogram (ECG) within previous 12 months or at baseline demonstrating no clinically significant conduction abnormalities and a QTc ≤440 ms (males) or ≤460 ms (females).
• Presence of Irritable Bowel Syndrome-like symptoms in the setting of quiescent disease (i.e., recurrent abdominal pain or discomfort on average at least 3 days per month in the past 3 months) and bowel dysfunction (i.e. either The Bristol Stool Form Scale (BSFS) 1-2 and/or 6-7) at least 25% of the time in the past 3 months.
• At least mild-moderate abdominal pain defined by PROMIS Belly Pain score greater than or equal to 55. (PROMIS score may be re-assed once, 7 days after initial score is recorded
• Stable Irritable Bowel Disease (IBD) medical therapy for at least the past 90 days (e.g., stable biologic, small molecule inhibitors or immunomodulator therapy with no planned changes or corticosteroids at enrollment).
• Willingness to begin study medication using the amitriptyline self-titration schedule (10 mg → 50 mg as tolerated).
• If personal history of anxiety and/or depression, stable dose of psychotropic medications for at least 6 months.
• Willingness to use effective mode of contraception (e.g., OCP, IUD) for the duration of the study in women of child-bearing age.
• Ability to complete electronic questionnaires, symptom diaries, and remote assessments using the REDCap platform.
• Ability to provide written or electronic informed consent prior to participating in any study procedures.

You may not qualify if:

• Active Crohn's disease, based on objective markers, endoscopic activity, or radiologic inflammation.
• Hospitalization for CD flare, bowel obstruction, or other significant disease activity within the protocol-defined timeframe prior to screening.
• Actively draining perianal fistula or perianal abscess requiring antibiotics, the presence of a draining seton, intra-abdominal abscess requiring antibiotics or surgical or radiographic drainage, entero-cutaneous fistula requiring active management, or other complications suggesting active inflammation.
• Any clinically significant stricture that could explain the IBS-like symptoms
• The presence of an ileostomy or colostomy.
• The presence of a J-pouch or other stool continent pouch (e.g., Koch pouch, continent ileostomy).
• Current use of tricyclic antidepressants (TCAs).
• Current use of monoamine oxidase inhibitors (MAOIs) or other medications that have a clinically significant interaction with amitriptyline.
• Current use of Cisapride.
• History of hypersensitivity or allergy to amitriptyline or other TCAs.
• Planned change in IBD maintenance therapy during the study period.
• Known cardiac conduction abnormalities, including:
• Prolonged QT interval defined as QTc \>440 ms in males or \>460 ms in females in previous 12 months or baseline ECGHistory of cardiac arrythmias, including Brugada syndrome, currently taking guanethidine or recent use of guanethidine in the past 14 days
• Recent history of myocardial infarction in the past 3 months
• Use of medications that significantly prolong QT interval (e.g., amiodarone, terfenadine, or sotalol), unless deemed safe by study medical oversight.

Sponsors & Collaborators

• University of Michigan: lead
• The Leona M. and Harry B. Helmsley Charitable Trust: collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Interventions

Amitriptyline

Intervention Hierarchy (Ancestors)

Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Allen A. Lee, MD, MS

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Shrinivas Bishu, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Prashant Singh, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Kinza Tareen, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charlie Bourque Jr.

CONTACT

(734) 615-3911; cabjr@med.umich.edu

Allen A. Lee, MD, MS

CONTACT

(734) 936-9454; allenlee@med.umich.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: multicenter, randomized, double-blind, placebo-controlled clinical trial

Study Record Dates

• First Submitted: April 22, 2026
• First Posted: April 29, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)