RecruitingPhase 2

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

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years to 65 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests whether amitriptyline is safe and helps ease belly pain, bloating, and bowel changes. It is for adults with Crohn's disease whose inflammation is controlled but who still have these symptoms.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be 18–65 years old with a confirmed diagnosis of Crohn's disease.
  • Have Crohn's disease controlled for at least 3 months, as judged by your care provider. A stool test, colonoscopy, or scan from the past 30 days must also show controlled disease.
  • Have belly pain or discomfort at least 3 days a month for the past 3 months, and hard or loose stools at least 25% of the time. Your belly pain survey score must be at least 55.
  • Have a heart tracing test (ECG) within the past year or at the start of the study that meets the study's heart rhythm safety limits.
  • Have unchanged Crohn's medicines for at least 90 days, with no planned changes and no steroid medicines at enrollment. If you have anxiety or depression, your mental health medicine doses must be unchanged for at least 6 months.
  • Be willing to start amitriptyline at 10 mg and increase it toward 50 mg as tolerated, following study instructions.
  • Use effective birth control during the study if you are a woman who can become pregnant.
  • Be able to complete online surveys, symptom diaries, and remote check-ins, and give written or electronic consent.

Who can't join

  • Have active Crohn's disease, a hospital stay for a flare or bowel blockage within the study's time limit, or certain active complications. These include draining tunnels or pockets of infection, bowel narrowing that could explain symptoms, or a surgically made stool opening or pouch.
  • Take a tricyclic antidepressant, cisapride, or another medicine that interacts with amitriptyline; have used an MAOI antidepressant or guanethidine in the past 14 days; or have an allergy to amitriptyline or similar drugs.
  • Have certain heart rhythm or electrical signal problems, or a heart attack in the past 3 months. Some medicines that affect heart rhythm are not allowed unless the study's medical team says they are safe.
  • Have active major depression, certain severe mental health conditions, suicidal thoughts in the past 3 months, a mental health hospital stay in the past year, or a history of seizures.
  • Be pregnant, breastfeeding, planning pregnancy during the study, or have a positive pregnancy test at screening.
  • Have a history of angle-closure glaucoma, an eye pressure problem; trouble emptying your bladder that required emergency or hospital care in the past 6 months; or a current or recent substance use disorder that could affect participation.
  • Plan to change your Crohn's treatment, or have joined another treatment study within the study's required waiting period.
  • Be unable or unwilling to follow study instructions or complete visits and assessments, or have another condition the study doctor believes would make participation unsafe or difficult.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion Criteria: * 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). Exclusion Criteria: Crohn's Disease-Related Exclusions * 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). Medication-Related Exclusions * 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. Cardiac and Safety Exclusions * 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. Psychiatric / Neurologic Exclusions * Evidence of active major depressive disorder, defined by depression score greater than or equal to 11 on the Hospital Anxiety and Depression Scale (HADS) * History of bipolar disorder, schizophrenia, obsessive-compulsive disorder, or other severe psychiatric conditions that may interfere with study participation * Active or passive suicidal ideation in the last 3 months. * Hospitalization for any psychiatric illness in the last year. * Personal history of seizures. * Currently taking a monoamine oxidase inhibitor (MAOI) or recent use of MAOI in the last 14 days. Other Medical Exclusions * Pregnancy, breastfeeding, or plans to become pregnant during the study period. * Positive urine pregnancy test at screening, if applicable. * History of angle-closure glaucoma. * History of urinary retention requiring hospitalization or emergency department (ED) visit in the last 6 months. * Current or recent substance use disorder that may interfere with participation. * Participation in another interventional clinical trial within the exclusion window * Inability or unwillingness to comply with study visits, medication instructions, electronic assessments, or follow-up requirements. * Any condition that, in the investigator's opinion, would interfere with the study or pose undue risks to the participant.

Study sites (1)

MI