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Pouch, IlealPhase 4PROP-ZEPNCT07756359

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

A Phase 4 study testing Tirzepatide, Loperamide and Diphenoxylate/Atropine in people with Pouch, Ileal and Pouches, Ileoanal, run by University of North Carolina, Chapel Hill at 5 sites in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Tirzepatide, Loperamide and Diphenoxylate/Atropine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
5 sitesUnited States
Study dates
Sep 2026to Sep 2027
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 22Show fewer
  • 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.

Trial locations and contacts

5 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Mikki Sandridge contact

919-843-3873

mikki_sandridge@med.unc.edu

5 sites in 1 country

United States5 sites

  • Cedars Sinai Medical Center

    Beverly Hills, California, 90211

    Melissa Myers, 310-423-0035, Melissa.Myers@cshs.org

    Andres Yarur, MD

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

    Mikki Sandridge, 919-843-3873, mikki_sandridge@med.unc.edu

    Edward Barnes, MD, MPH

  • Mayo Clinic

    Rochester, Minnesota, 55905

    Chad Rypstra, 507-538-4289, Rypstra.Chad@mayo.edu

    Laura Raffals, MD

  • University of Utah

    Salt Lake City, Utah, 84112

    Lynette Holman, 801-585-9155, Lynette.holman@hsc.utah.edu

    Priscila Santiago, MD

  • Washington University School of Medicine

    St Louis, Missouri, 63110

    Katherine Huang, 314-273-0301, luluhuang@wustl.edu

    Parakkal Deepak, MD

Other trials in United States

About this study

Official title: 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)

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.

Being tested
Tirzepatide, Loperamide, Diphenoxylate/Atropine
Keywords
High Bowel Frequency, IPAA, ileal pouch-anal anastomosis
Medical subject headings
Inflammatory Bowel Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TirzepatideDrug

    Also called Zepbound

    Tirzepatide will be administered subcutaneously

  • LoperamideDrug

    Also called Imodium

    2 mg orally every 6 hours as needed

  • Diphenoxylate/AtropineDrug

    Also called Lomotil

    2 mg orally every 6 hours

Study groups in NCT07756359
Study groupRoleWhat they receive
TirzepatideExperimentalTreatment 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.
Receives: Drug: Tirzepatide
Optimized Standard of Care anti-diarrheal therapyActive comparatorOptimized 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.
Receives: Drug: Tirzepatide; Drug: Loperamide; Drug: Diphenoxylate/Atropine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Week 12 (Week 16 if applicable)

Secondary outcomes (9)

  1. 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.

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

  2. 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.

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

  3. 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.

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

  4. 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

    Measured: Up to Week 12 (Week 16 if applicable)

  5. Number of Participants with worsening laboratory values

    Number of participants with worsening fecal calprotectin laboratory values will be reported.

    Measured: Up to Week 12 (Week 16 if applicable)

  6. Number of Participants with changes in nausea

    Number of participants with self described changes in nausea will be reported

    Measured: Up to Week 12 (Week 16 if applicable)

  7. Number of Participants with changes in appetite

    Number of participants with self described changes in appetite will be reported

    Measured: Up to Week 12 (Week 16 if applicable)

  8. Number of Participants with changes in abdominal pain

    Number of participants with self described changes in abdominal pain will be reported

    Measured: Up to Week 12 (Week 16 if applicable)

  9. Number of Participants with changes in well-being

    Number of participants with self described changes in well being will be reported

    Measured: Up to Week 12 (Week 16 if applicable)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2026
  2. Study startSep 2026 (estimated)
  3. Primary completionSep 2027 (estimated)
  4. Study completionSep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07756359
Sponsor's protocol ID
26-0425
Acronym
PROP-ZEP
Status last verified
Aug 2026
First submitted
4 Aug 2026
Last updated
10 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Deidentified individual data that supports the results will be shared beginning 9 and continuing for 12 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.

Publications

  • https://uspl.lilly.com/zepbound/zepbound.html#pi

  • Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, Mao H, Zhang S, Ahmad NN, Bunck MC, Benabbad I, Zhang XM; SURMOUNT-2 investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023 Aug 19;402(10402):613-626. doi: 10.1016/S0140-6736(23)01200-X. Epub 2023 Jun 26.

    PubMed 37385275

  • Yamamoto T, Shimoyama T, Bamba T, Matsumoto K. Consecutive Monitoring of Fecal Calprotectin and Lactoferrin for the Early Diagnosis and Prediction of Pouchitis after Restorative Proctocolectomy for Ulcerative Colitis. Am J Gastroenterol. 2015 Jun;110(6):881-7. doi: 10.1038/ajg.2015.129. Epub 2015 Apr 28.

    PubMed 25916224

  • Barnes EL, Long MD, Raffals L, Isaacs K, Stidham RW, Herfarth HH; Contributors. Development of the Endoscopic Pouch Score for Assessment of Inflammatory Conditions of the Pouch. Clin Gastroenterol Hepatol. 2023 Jun;21(6):1663-1666.e3. doi: 10.1016/j.cgh.2022.04.026. Epub 2022 May 12.

    PubMed 35568303

  • Dubinsky MC, Panaccione R, Lewis JD, Sands BE, Hibi T, Lee SD, Naegeli AN, Shan M, Green LA, Morris N, Arora V, Bleakman AP, Belin R, Travis S. Impact of Bowel Urgency on Quality of Life and Clinical Outcomes in Patients With Ulcerative Colitis. Crohns Colitis 360. 2022 Jun 3;4(3):otac016. doi: 10.1093/crocol/otac016. eCollection 2022 Jul.

    PubMed 36777426

  • Xu W, Ye H, Zhu Y, Ding W, Fu J, Cui L, Du P. Long-term quality of life associated with early surgical complications in patients with ulcerative colitis after ileal pouch-anal anastomosis: A single-center retrospective study. Int J Surg. 2017 Dec;48:174-179. doi: 10.1016/j.ijsu.2017.10.070. Epub 2017 Nov 8.

    PubMed 29104126

  • Stewart AL, Hays RD, Ware JE Jr. The MOS short-form general health survey. Reliability and validity in a patient population. Med Care. 1988 Jul;26(7):724-35. doi: 10.1097/00005650-198807000-00007. No abstract available.

    PubMed 3393032

  • Barnes EL, Boynton MH, DeWalt DA, Herfarth HH, Kappelman MD. Patient Reported Outcome Assessments Used in the Evaluation of Patients after Ileal Pouch-Anal Anastomosis: A Systematic Review. Gastro Hep Adv. 2023;2(8):1044-1049. doi: 10.1016/j.gastha.2023.07.010. Epub 2023 Jul 29.

    PubMed 38125203

  • Shen B, Remzi FH, Lopez AR, Queener E. Rifaximin for maintenance therapy in antibiotic-dependent pouchitis. BMC Gastroenterol. 2008 Jun 23;8:26. doi: 10.1186/1471-230X-8-26.

    PubMed 18573211

  • Mimura T, Rizzello F, Helwig U, Poggioli G, Schreiber S, Talbot IC, Nicholls RJ, Gionchetti P, Campieri M, Kamm MA. Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut. 2004 Jan;53(1):108-14. doi: 10.1136/gut.53.1.108.

    PubMed 14684584

  • Kuhbacher T, Ott SJ, Helwig U, Mimura T, Rizzello F, Kleessen B, Gionchetti P, Blaut M, Campieri M, Folsch UR, Kamm MA, Schreiber S. Bacterial and fungal microbiota in relation to probiotic therapy (VSL#3) in pouchitis. Gut. 2006 Jun;55(6):833-41. doi: 10.1136/gut.2005.078303. Epub 2006 Jan 9.

    PubMed 16401690

  • Gionchetti P, Rizzello F, Venturi A, Ugolini F, Rossi M, Brigidi P, Johansson R, Ferrieri A, Poggioli G, Campieri M. Antibiotic combination therapy in patients with chronic, treatment-resistant pouchitis. Aliment Pharmacol Ther. 1999 Jun;13(6):713-8. doi: 10.1046/j.1365-2036.1999.00553.x.

    PubMed 10383499

  • Gionchetti P, Rizzello F, Venturi A, Brigidi P, Matteuzzi D, Bazzocchi G, Poggioli G, Miglioli M, Campieri M. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology. 2000 Aug;119(2):305-9. doi: 10.1053/gast.2000.9370.

    PubMed 10930365

  • Gionchetti P, Rizzello F, Morselli C, Poggioli G, Tambasco R, Calabrese C, Brigidi P, Vitali B, Straforini G, Campieri M. High-dose probiotics for the treatment of active pouchitis. Dis Colon Rectum. 2007 Dec;50(12):2075-82; discussion 2082-4. doi: 10.1007/s10350-007-9068-4. Epub 2007 Oct 13.

    PubMed 17934776

  • Gionchetti P, Rizzello F, Helwig U, Venturi A, Lammers KM, Brigidi P, Vitali B, Poggioli G, Miglioli M, Campieri M. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology. 2003 May;124(5):1202-9. doi: 10.1016/s0016-5085(03)00171-9.

    PubMed 12730861

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Tirzepatide, Loperamide and Diphenoxylate/Atropine in people with Pouch, Ileal and Pouches, Ileoanal, run by University of North Carolina, Chapel Hill at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Mikki Sandridge (919-843-3873, mikki_sandridge@med.unc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07756359, which also lists 58 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2026.

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