Amitriptyline for IBS-like Symptoms in Quiescent Crohn's Disease: A Multicenter Randomized Placebo-Controlled Trial
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.
• 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.
• Stable 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).