Efficacy of the Dual GIP - GLP-1 Receptor Agonist Tirzepatide in Patients With an Ileal Pouch-anal Anastomosis (IPAA) and Chronic High Bowel Frequency (I8F-NS-X008)
Trial Snapshot
- Phase
- Phase 4
- Status
- Not yet recruiting
- Enrollment
- 20
- Locations
- 5
- Primary Endpoint
- Proportion of patients achieving a decrease of the average daily bowel frequency by 30% at week 12 (Week 16 if applicable)
Study Overview
Brief Summary
The goal of this clinical trial is to learn if Tirzepatide (Zepbound) can decrease bowel frequency in patients that have an ileal-pouch anal anastomosis (IPAA or pouch) better than standard of care anti-diarrheal therapy.
The main question it aims to answer is:
Does Tirzepatide reduce bowel frequency better than standard of care anti-diarrheal therapy in patients that have a pouch
Participants will:
Visit the clinic 5 times, answer questions about symptoms daily, be assigned to take the study product as instructed and provide a stool sample 4 times.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Informed consent will be obtained before any study-related procedures
- •Age > 18 and <80 years
- •Patients with an IPAA and bowel frequency > 8 bowel movements in 24 hours on at least 4 of 7 days/week (and/or an average of >8 bowel movements in the 7 days preceding enrollment)
- •Patients must have demonstrated high bowel frequency despite adequate therapy for high bowel frequency with loperamide 2 mg orally every 6 hours as needed (at least 3 doses daily) and/or diphenoxylate/atropine 2 mg orally every 6 hours as needed (at least 3 doses daily) or proven intolerance to these anti-diarrheal medications.
- •Among patients with inflammatory conditions of the pouch, high bowel frequency must be demonstrated despite adequate therapy for intermittent pouchitis, chronic pouchitis, or Crohn's like disease of the pouch. Adequate therapy is required to ensure significant pouch inflammation is not a driver of high bowel frequency (described in
Exclusion Criteria
- •Participants with a proven history of ulcerative colitis and history of 1,2, modified -2 or 3 stage IPAA and ileostomy takedown
- •Ability to access internet for electronic database entry
- •Exclusion Criteria:
- •Prior exposure to tirzepatide or other GLP-1RA
- •BMI <20 at the time of study screening
- •Personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2
- •Known hypersensitivity to tirzepatide or its metabolites
- •Significant pouch inflammation defined as an endoscopic pouch disease activity index (PDAI ) ≥ 4
- •Known stricture of the ileo-anal anastomosis or afferent limb stricture
- •New onset of high bowel frequency in the setting of acute pouchitis
- •Final stage of IPAA surgery < 6 months prior to enrollment
- •Current infection with Clostridioides difficile
- •Known HIV or active Hepatitis B/C
- •Clinically significant liver disease (Primary Sclerosing Cholangitis with LFT's <1.5 upper limit of normal can be included)
- •Severe hepatic impairment, defined as Child-Pugh Class C
- •Known clinically significant chronic nausea and/or vomiting in the past
- •Known diagnosis of type 1 or type 2 diabetes
- •Known decreased kidney function with a glomerular filtration rate <30 ml/min/1.732
- •History of malignancy, except for basal cell carcinoma, non-metastatic squamous cell carcinoma of the skin, or prior malignancy with curative therapy completed at least 5 years prior to screening and no recurrence.
- •New York Heart Association class 3 or greater heart failure or recent (within 6 months) cardiovascular event
- •Prior history of pancreatitis
- •Clinically significant laboratory results at screening or baseline, as judged by the Investigator from local testing.
- •Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
- •Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days before screening.
- •Any disorder, which in the investigator's opinion might jeopardize participant's safety or compliance with the protocol.
Arms & Interventions
Tirzepatide
Treatment will start at 2.5 mg once weekly. After 4 weeks, the dose will be increased to 5 mg once weekly. After another 4 weeks, the dose will be increased to 7.5 mg once weekly for 4 weeks.
Intervention: Tirzepatide (Drug)
Optimized Standard of Care anti-diarrheal therapy
Optimized regimen of loperamide 2 mg orally every 6 hours as needed for increased frequency or diphenoxylate/atropine can be given 2 mg orally every 6 hours. When using either or both therapies in combination the participant should not exceed a maximum dose of 16 mg orally within 24 hours. For participants with continued or worsening high bowel frequency for >2 weeks, transition to active therapy with tirzepatide will be offered at week 4. Tirzepatide treatment would begin as 2.5 mg once weekly. After 4 weeks, the dose will be increased to 5 mg once weekly. After another 4 weeks, the dose will be increased to 7.5 mg once weekly for 4 weeks.
Intervention: Diphenoxylate/Atropine (Drug)
Optimized Standard of Care anti-diarrheal therapy
Optimized regimen of loperamide 2 mg orally every 6 hours as needed for increased frequency or diphenoxylate/atropine can be given 2 mg orally every 6 hours. When using either or both therapies in combination the participant should not exceed a maximum dose of 16 mg orally within 24 hours. For participants with continued or worsening high bowel frequency for >2 weeks, transition to active therapy with tirzepatide will be offered at week 4. Tirzepatide treatment would begin as 2.5 mg once weekly. After 4 weeks, the dose will be increased to 5 mg once weekly. After another 4 weeks, the dose will be increased to 7.5 mg once weekly for 4 weeks.
Intervention: Loperamide (Drug)
Optimized Standard of Care anti-diarrheal therapy
Optimized regimen of loperamide 2 mg orally every 6 hours as needed for increased frequency or diphenoxylate/atropine can be given 2 mg orally every 6 hours. When using either or both therapies in combination the participant should not exceed a maximum dose of 16 mg orally within 24 hours. For participants with continued or worsening high bowel frequency for >2 weeks, transition to active therapy with tirzepatide will be offered at week 4. Tirzepatide treatment would begin as 2.5 mg once weekly. After 4 weeks, the dose will be increased to 5 mg once weekly. After another 4 weeks, the dose will be increased to 7.5 mg once weekly for 4 weeks.
Intervention: Tirzepatide (Drug)
Outcomes
Primary Outcomes
Proportion of patients achieving a decrease of the average daily bowel frequency by 30% at week 12 (Week 16 if applicable)
Time Frame: Week 12 (Week 16 if applicable)
Daily bowel frequency will be calculated by the median 24 hour bowel frequency over the 7 days prior to the week 12 assessment; to be eligible for this calculation, participants will need to complete stool diaries on at least 4 of the 7 days. Note: A 30% reduction will equate to 3-4 bowel movements in a 24-hour time period for the anticipated eligible population
Secondary Outcomes
- The proportion of patients achieving an average bowel frequency of ≤8 bowel movements daily.(Week 1, Week 4, Week 8, Week 12, Week 16 (if applicable))
- Change in Cleveland Clinic Global Quality of Life (QoL) scale(Week 1, Week 4, Week 8, Week 12 (Week 16 if applicable))
- Change in Patient-Reported Outcomes Measurement Information System (PROMIS) incontinence measure(Week 1, Week 4, Week 8, Week 12 (Week 16 if applicable))
- Number of Participants with AEs, SAEs and AEs Leading to Discontinuation of Study Intervention(Up to Week 12 (Week 16 if applicable))
- Number of Participants with worsening laboratory values(Up to Week 12 (Week 16 if applicable))
- Number of Participants with changes in nausea(Up to Week 12 (Week 16 if applicable))
- Number of Participants with changes in appetite(Up to Week 12 (Week 16 if applicable))
- Number of Participants with changes in abdominal pain(Up to Week 12 (Week 16 if applicable))
- Number of Participants with changes in well-being(Up to Week 12 (Week 16 if applicable))