Quiescent Crohn's Disease (CD)
Amitriptyline for IBS-Like Symptoms in Crohn's Disease Remission
This study is investigating the safety and symptom effects of daily amitriptyline compared with placebo in adults with Crohn's disease in remission who have ongoing abdominal pain and bowel dysfunction.
Registry title: Amitriptyline for IBS-like Symptoms in Quiescent Crohn's Disease
1 recruiting U.S. site ↓Study at a glance
- Age
- 18 Years–65 Years
- Treatment
- Amitriptyline or Placebo
- Design
- Randomized · Quadruple
- Central study contact
- Charlie Bourque Jr.(734) 615-3911cabjr@med.umich.edu
- Sponsor
- University of Michigan
Research question
In adults with Crohn's disease in remission and continuing IBS-like symptoms, how safe is amitriptyline and how does it affect abdominal pain and overall symptom severity compared with placebo by Week 24?
Participant snapshot
Who the study is looking for
- The study is looking for adults ages 18 through 65 with an established diagnosis of Crohn's disease.
- The study is looking for people whose Crohn's disease has been judged to be in remission for the past three months and supported by recent biochemical, endoscopic, or radiographic evidence.
- The study is looking for people who still have recurrent abdominal pain or discomfort and specified bowel-pattern changes despite quiescent Crohn's disease.
- The study is looking for people whose inflammatory bowel disease treatment has been stable for at least 90 days, with no planned changes.
- The listed recruiting location is the University of Michigan in Ann Arbor, Michigan.
Participation overview
What participation may involve
Participants take either amitriptyline or matching placebo once daily, adjust the dose during the first six weeks as tolerated, complete electronic symptom assessments, and are evaluated for safety and digestive symptoms through Week 24. What participation may involve: - Take the assigned amitriptyline or placebo orally once each day. - Self-adjust the assigned dose from 10 mg up to 50 mg during the first six weeks, as tolerated. - Complete electronic questionnaires, symptom diaries, and remote assessments using REDCap. - Complete assessments of abdominal pain, overall symptom severity, and serious adverse events by Week 24. The assigned amitriptyline or placebo is continued through Week 24; the registry does not state whether any follow-up continues afterward.
Study interventions
What participants may receive or do
- Amitriptyline: Participants assigned to this group take amitriptyline by mouth once daily. They begin at 10 mg, may increase the dose as tolerated to a maximum of 50 mg during the first six weeks, and then continue their highest tolerated dose through Week 24.
- Placebo: Participants assigned to this group take visually matching placebo capsules or tablets. The placebo follows the same once-daily self-titration schedule, from 10 mg to a maximum of 50 mg as tolerated, through Week 24.
Study design
How the comparison works
This Phase 2 study plans to enroll about 100 participants at multiple centers and compare parallel amitriptyline and placebo groups through Week 24. Participants are assigned randomly to one of two parallel groups. The registry describes roughly 50 participants in each group. Participants, care providers, investigators, and outcome assessors are masked to group assignment. Amitriptyline and placebo are designed to look alike. The amitriptyline group is compared with a placebo group following a matching dose-adjustment schedule. The placebo contains no amitriptyline and is described as visually indistinguishable from the study drug. The exact chance of receiving placebo is not explicitly stated.
Reported activities
Procedures and tests
- A 12-lead electrocardiogram (ECG) completed within the previous 12 months or at baseline must show no clinically significant conduction abnormality and must meet the stated corrected QT interval limits.
- Screening must confirm Crohn's disease remission using recent fecal calprotectin, colonoscopy findings, or radiographic evidence as specified by the protocol.
- Abdominal pain severity is assessed with the Patient-Reported Outcomes Measurement Information System (PROMIS) Belly Pain score.
- Overall symptom severity is assessed using the Irritable Bowel Syndrome Severity Scoring System questionnaire.
- Participants must complete electronic questionnaires, symptom diaries, and remote assessments through REDCap.
- When applicable, a urine pregnancy test is used at screening.
- The study records serious adverse events involving hospitalization, an emergency department visit, suicidal ideation, or hallucinations when considered probably or definitely related to study medication.
Eligibility highlights
Details that may affect whether you contact the study
These are selected highlights, not a complete eligibility check. Exact criteria remain in the full registry record below.
Common requirements
- Participants must be 18 through 65 years old when they consent.
- An established Crohn's disease diagnosis must be confirmed using standard clinical, endoscopic, tissue, or imaging criteria.
- A provider must judge the Crohn's disease to have been in remission for the past three months, with qualifying biochemical, endoscopic, or radiographic evidence within the stated timeframe.
- Qualifying remission evidence includes fecal calprotectin below 150 mcg/g, specified colonoscopy scores without large ulcers, or protocol-consistent radiographic evidence.
- A recent or baseline ECG must show no clinically significant conduction problem and a corrected QT interval no higher than 440 ms for males or 460 ms for females.
- Participants must have recurrent abdominal pain or discomfort averaging at least three days per month during the past three months, plus the specified hard or loose stool patterns at least 25% of the time.
- The PROMIS Belly Pain score must be at least 55; the criterion says it may be reassessed once seven days after the first score.
- Inflammatory bowel disease medication must have been stable for at least 90 days, with no planned changes and no corticosteroids at enrollment.
- Participants must be willing to follow the amitriptyline self-titration schedule from 10 mg up to 50 mg as tolerated.
- People with a personal history of anxiety or depression must have taken a stable dose of psychotropic medication for at least six months.
- Participants must be able to complete electronic questionnaires, symptom diaries, and remote REDCap assessments.
Possible reasons someone may not be able to join
- People with active Crohn's disease based on objective markers, endoscopy, or imaging are excluded.
- Recent hospitalization for a Crohn's flare, bowel obstruction, or other significant disease activity within the protocol-defined timeframe is exclusionary.
- Specified active fistulas, abscesses, draining setons, or other complications suggesting active inflammation are exclusionary.
- A clinically significant stricture that could explain the IBS-like symptoms is exclusionary.
- People with an ileostomy, colostomy, J-pouch, or another stool-continent pouch are excluded.
- Current tricyclic antidepressant use, current monoamine oxidase inhibitor use, or another clinically significant medication interaction with amitriptyline is exclusionary.
- Amitriptyline or other tricyclic antidepressant allergy or hypersensitivity is exclusionary.
- Specified heart rhythm or conduction problems, a recent heart attack, or use of medications that significantly prolong the QT interval may exclude someone.
- Active major depression by the stated Hospital Anxiety and Depression Scale threshold, recent suicidal ideation, specified severe psychiatric conditions, or psychiatric hospitalization in the past year are exclusionary.
- A personal history of seizures is exclusionary.
- Pregnancy, breastfeeding, plans for pregnancy during the study, or an applicable positive screening pregnancy test are exclusionary.
- Participation in another interventional clinical trial within the study's unspecified exclusion window is exclusionary.
Important unknowns
What the record does not make clear
- The registry does not state how many in-person or remote visits occur or when they are scheduled.
- Study medication continues through Week 24, but the registry does not say whether screening or follow-up extends the total participation period.
- The registry describes roughly 50 participants in each arm but does not explicitly state each participant's probability of assignment to placebo.
- Stable inflammatory bowel disease therapy is required, but the registry does not fully explain which treatments continue during the study or how medically necessary changes are handled.
- The registry does not describe rescue treatment for worsening abdominal symptoms or a Crohn's disease flare.
- Colonoscopy is one possible way to document remission, but the registry does not say whether a new study-related colonoscopy is required.
- The registry does not state which study-related or routine-care costs are covered or billed to insurance.
- The registry does not report whether participants are compensated.
- The registry does not describe reimbursement or support for travel, parking, lodging, or meals.
- Remote assessments are required, but the registry lists an Ann Arbor site and does not say how much of the study can be completed remotely.
- The registry does not describe access to amitriptyline or unmasking after study participation ends.
- The criterion concerning recent hospitalization uses a protocol-defined timeframe that is not included in the registry record.
Before contacting the site
Questions for the study team
- How many study visits are required, when do they occur, and which visits must be completed in person?
- What is the exact chance of assignment to placebo, and when will participants learn which group they were in?
- Which current Crohn's medications must remain unchanged, and what happens if a change becomes medically necessary?
- Will screening or participation require a new colonoscopy, imaging study, fecal calprotectin test, or ECG?
- What happens if abdominal symptoms worsen, Crohn's disease becomes active, or side effects occur during dose increases?
- Which study-related costs are covered, is compensation provided, and is travel or parking support available?
- What is the complete medication interaction review, including the required timing for stopping any prohibited medicines?
Before changing care
Questions for your gastroenterologist
- Is my Crohn's disease stable enough to discuss this study, and which records best document remission?
- Could amitriptyline interact with my current medicines or pose concerns based on my heart, psychiatric, neurologic, eye, or urinary history?
- Would keeping my current Crohn's treatment stable for the study be clinically appropriate, and how should necessary changes be coordinated?
- What approved alternatives could be considered for my ongoing abdominal pain and bowel symptoms outside this trial?
- If I contact the study team, how should you and the research clinicians coordinate monitoring for a Crohn's flare, medication side effects, or mood changes?
This plain-language digest is provided by the Aidy clinical trials API. It may omit details and is not medical advice or an eligibility decision. Review the full registry record and confirm details with the study team.
Source record
Full registry record
The sections below preserve the study information supplied through ClinicalTrials.gov, including complete descriptions, criteria, outcomes, and locations.
About this study
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.
Study design and administration
- Organization
- University of Michigan
- Organization class
- Other
- Organization study ID
- HUM00265477
- Lead sponsor
- University of Michigan
- Sponsor class
- Other
- Enrollment type
- Estimated
- Allocation
- Randomized
- Intervention model
- Parallel
- Primary purpose
- Treatment
- Masking
- Quadruple
- Who is masked
- Participant, Care Provider, Investigator, Outcomes Assessor
- Standard age groups
- Adult, Older Adult
Study arms
Experimental
Amitriptyline
Roughly 50 participants
Interventions: Drug: Amitriptyline
Placebo Comparator
Placebo
Roughly 50 participants
Interventions: Drug: Placebo
Interventions
Drug
Amitriptyline
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.
Drug
Placebo
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.
Eligibility
18 Years–65 Years
All
Not accepted
Inclusion criteria (16)
- Age 18-65 years, inclusive, at the time of consent.Registry-derived · unreviewed
- Established diagnosis of Crohn's disease, confirmed by standard clinical, endoscopic, histologic, and/or radiologic criteria.Registry-derived · unreviewed
- 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:Registry-derived · unreviewed
- Biochemical remission defined by fecal calprotectin \< 150 mcg/g, ORRegistry-derived · unreviewed
- 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). ORRegistry-derived · unreviewed
- Radiographic evidence of quiescent disease consistent with the protocol.Registry-derived · unreviewed
- 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).Registry-derived · unreviewed
- 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.Registry-derived · unreviewed
- 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 recordedRegistry-derived · unreviewed
- 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).Registry-derived · unreviewed
- Willingness to begin study medication using the amitriptyline self-titration schedule (10 mg → 50 mg as tolerated).Registry-derived · unreviewed
- If personal history of anxiety and/or depression, stable dose of psychotropic medications for at least 6 months.Registry-derived · unreviewed
- Willingness to use effective mode of contraception (e.g., OCP, IUD) for the duration of the study in women of child-bearing age.Registry-derived · unreviewed
- Ability to complete electronic questionnaires, symptom diaries, and remote assessments using the REDCap platform.Registry-derived · unreviewed
- Ability to provide written or electronic informed consent prior to participating in any study procedures.Registry-derived · unreviewed
- 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).Registry-derived · unreviewed
Exclusion criteria (28)
- Active Crohn's disease, based on objective markers, endoscopic activity, or radiologic inflammation.Registry-derived · unreviewed
- Hospitalization for CD flare, bowel obstruction, or other significant disease activity within the protocol-defined timeframe prior to screening.Registry-derived · unreviewed
- 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.Registry-derived · unreviewed
- Any clinically significant stricture that could explain the IBS-like symptomsRegistry-derived · unreviewed
- The presence of an ileostomy or colostomy.Registry-derived · unreviewed
- The presence of a J-pouch or other stool continent pouch (e.g., Koch pouch, continent ileostomy).Registry-derived · unreviewed
- Current use of tricyclic antidepressants (TCAs).Registry-derived · unreviewed
- Current use of monoamine oxidase inhibitors (MAOIs) or other medications that have a clinically significant interaction with amitriptyline.Registry-derived · unreviewed
- Current use of Cisapride.Registry-derived · unreviewed
- History of hypersensitivity or allergy to amitriptyline or other TCAs.Registry-derived · unreviewed
- Planned change in IBD maintenance therapy during the study period.Registry-derived · unreviewed
- Known cardiac conduction abnormalities, including:Registry-derived · unreviewed
- 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 daysRegistry-derived · unreviewed
- Recent history of myocardial infarction in the past 3 monthsRegistry-derived · unreviewed
- Use of medications that significantly prolong QT interval (e.g., amiodarone, terfenadine, or sotalol), unless deemed safe by study medical oversight.Registry-derived · unreviewed
- Evidence of active major depressive disorder, defined by depression score greater than or equal to 11 on the Hospital Anxiety and Depression Scale (HADS)Registry-derived · unreviewed
- History of bipolar disorder, schizophrenia, obsessive-compulsive disorder, or other severe psychiatric conditions that may interfere with study participationRegistry-derived · unreviewed
- Active or passive suicidal ideation in the last 3 months.Registry-derived · unreviewed
- Hospitalization for any psychiatric illness in the last year.Registry-derived · unreviewed
- Personal history of seizures.Registry-derived · unreviewed
- Currently taking a monoamine oxidase inhibitor (MAOI) or recent use of MAOI in the last 14 days.Registry-derived · unreviewed
- Pregnancy, breastfeeding, or plans to become pregnant during the study period.Registry-derived · unreviewed
- Positive urine pregnancy test at screening, if applicable.Registry-derived · unreviewed
- History of angle-closure glaucoma.Registry-derived · unreviewed
- History of urinary retention requiring hospitalization or emergency department (ED) visit in the last 6 months.Registry-derived · unreviewed
- Current or recent substance use disorder that may interfere with participation.Registry-derived · unreviewed
- Inability or unwillingness to comply with study visits, medication instructions, electronic assessments, or follow-up requirements.Registry-derived · unreviewed
- Any condition that, in the investigator's opinion, would interfere with the study or pose undue risks to the participant.Registry-derived · unreviewed
This information can identify a possible match, conflict, or item needing confirmation. Only the study team can determine eligibility.
Study outcomes
Primary outcome
Safety reported as the proportion of participants experiencing a serious adverse event (SAE),
Time frame: Week 24
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.
Secondary outcome
Efficacy in Abdominal Pain
Time frame: Week 24
Assessed using the PROMIS Belly Pain score which range from 5-25 and higher scores indicate worse symptoms.
Secondary outcome
Global Symptom Improvement
Time frame: Week 24
Assessed using The Irritable Bowel Severity Scoring System (IBS-SSS) is a questionnaire used for evaluating the severity of IBS with a maximum score of 500. Higher scores indicate increased pain.
Recruiting locations in the United States
University of Michigan
RecruitingAnn Arbor, Michigan, 48109, United States
Allen A. Lee, MD, MS734-936-9454allenlee@med.umich.edu
Central study contacts
Registry dates
- First posted
- Apr 29, 2026
- Primary completion
- Dec 2029
- Overall completion
- Dec 2029
Trial information comes from ClinicalTrials.gov and may change. Confirm current status, eligibility, and site details with the study team. Aidy does not provide medical advice or determine eligibility.