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

NCT07756359 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 26-0425
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

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.

Conditions

Pouch, Ileal; Pouches, Ileoanal; Bowel Diseases, Inflammatory

Keywords

High Bowel Frequency; IPAA; ileal pouch-anal anastomosis

Outcome Measures

Primary Outcomes (1)

• 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

  Week 12 (Week 16 if applicable)

Secondary Outcomes (9)

• 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)

Study Arms (2)

Tirzepatide

EXPERIMENTAL

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.

Drug: Tirzepatide

Optimized Standard of Care anti-diarrheal therapy

ACTIVE COMPARATOR

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.

Drug: Tirzepatide; Drug: Loperamide; Drug: Diphenoxylate/Atropine

Interventions

Tirzepatide DRUG

Tirzepatide will be administered subcutaneously

Also known as: Zepbound

Optimized Standard of Care anti-diarrheal therapy; Tirzepatide

Loperamide DRUG

2 mg orally every 6 hours as needed

Also known as: Imodium

Optimized Standard of Care anti-diarrheal therapy

Diphenoxylate/Atropine DRUG

2 mg orally every 6 hours

Also known as: Lomotil

Optimized Standard of Care anti-diarrheal therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Eli Lilly and Company: collaborator

Study Sites (5)

Cedars Sinai Medical Center

Beverly Hills, California, 90211, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (58)

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MeSH Terms

Conditions

Inflammatory Bowel Diseases

Interventions

Tirzepatide; Loperamide; atropine sulfate-diphenoxylate hydrochloride drug combination

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Edward Barnes, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mikki Sandridge

CONTACT

919-843-3873; mikki_sandridge@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2026
• First Posted: August 10, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: August 10, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 9 and continuing for 12 months following publication
• Access Criteria: Investigator has approved IRB, IEC, or REB and an executed data use/ sharing agreement with UNC.

Locations

US (5)