Tirzepatide for Ileal Pouch-anal Anastomosis (IPAA) and Chronic High Bowel Frequency (I8F-NS-X008)

Phase 4Not Yet RecruitingNCT07756359

University of North Carolina, Chapel Hill20 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Pouch, Ileal Pouches, Ileoanal Bowel Diseases, Inflammatory

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Locations (5)

Cedars Sinai Medical Center

Beverly Hills, California, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of North Carolina

Chapel Hill, North Carolina, United States

University of Utah

Salt Lake City, Utah, United States

Outcomes

Primary Outcomes

Proportion of patients achieving a decrease of the average daily bowel frequency by 30% at 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

Time frame: Week 12 (Week 16 if applicable)

Secondary Outcomes

The proportion of patients achieving an average bowel frequency of ≤8 bowel movements daily.

Daily bowel frequency will be calculated by the median 24 hour bowel frequency over the 7 days prior to the assessment; to be eligible for this calculation, participants will need to complete stool diaries on at least 4 of the 7 days.

Time frame: Week 1, Week 4, Week 8, Week 12, Week 16 (if applicable)

Change in Cleveland Clinic Global Quality of Life (QoL) scale

The Cleveland Clinic Global Quality of Life scale asks the patient to rate their current QoL, current quality of health, and current energy level using a 1-10 rating (where 10 is best). The score on each of these 3 components is added and the final Cleveland Clinic Global Quality of Life utility score can be obtained by dividing this result by 30. A higher score means improved quality of life.

Time frame: Week 1, Week 4, Week 8, Week 12 (Week 16 if applicable)

Change in Patient-Reported Outcomes Measurement Information System (PROMIS) incontinence measure

The PROMIS measure for incontinence includes 4 items that assess the frequency of bowel incontinence, soiling, stool leakage, and stool leakage while passing gas over the past 7 days. Score range is 0-20, where a higher score means increased incontinence.

Time frame: 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

An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, results in another serious or important medical event