NCT04763564

Efficacy of Liraglutide Therapy in Patients With IPAA

Efficacy of Liraglutide Therapy in Patients With an Ileal -Pouch Anal Anastomosis (IPAA) and Chronic High Bowel Frequency

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: University of North Carolina, Chapel Hill · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Patients with an ileal pouch-anal anastomosis(IPAA; pouch) due to refractory inflammatory bowel disease and increased bowel frequency in the absence of significant pouch inflammation will be randomized to liraglutide or placebo in a prospective cross over study.

Detailed description

Randomized, double-blind, 2-period, placebo- controlled, crossover proof of concept study. Ten patients with increased bowel frequency defined as bowel frequency \> 8 bowel movements in 24 hours on at least 4 of 7 days/week and presence of high bowel frequency \> 4 weeks despite adequate therapy for acute pouchitis or Crohn's like disease of the pouch will be randomized to either liraglutide or placebo treatment for 6 weeks (Period 1). Subjects will be randomized 1:1 to 1 of 2 treatment sequences, liraglutide-placebo or placebo-liraglutide, and receive either liraglutide or volume-matched placebo. After a wash-out period of at least 5 days (the half-life of liraglutide is 11-12 hours, thus the minimal washout period of 5 days is equal to 10 half-life's) patients will be crossed over to the other treatment arm (Period 2). Since high bowel frequency can result in significant malaise and dehydration, patients not responding to the respective therapies in period 1 may be crossed over after 4 weeks of therapy or in period 2 can be terminated early at week 4. The rationale behind the early termination is based on 2 open-label cohorts reporting the efficacy of liraglutide or exenatide in patients with high output ileostomies (the patient group the most comparable to the pouch patient population). Glucagon-like peptide- 1 (GLP-1) receptor agonist therapy even at the lowest dose showed an almost immediate effect reducing the ostomy output after 1-3 days in most patients.Thus, patients not responding to a 4-week therapy with a GLP-1receptor agonist are highly unlikely to respond if the therapy would be continued.

Conditions

• Pouchitis
• Irritable Pouch Syndrome

Interventions

Type	Name	Description
DRUG	Liraglutide Pen Injector	Treatment will be initiated at 0.6 mg per day for one week. The patient will be instructed to increase the dose to 1.2/day and 1.8 mg /day in week 2 and in week 3, respectively. From week 3 after the start of the drug until week 6 the patient will apply 1.8 mg/day liraglutide. In case of intolerance (e.g. occurrence of refractory nausea) at a higher dose (e.g. 1.8 mg daily, the highest dose in this trial) liraglutide can be reduced to the previous level.
DRUG	Placebo Pen Injector	Matching placebo pens used to administer normal saline in the same fashion as for liraglutide

Timeline

• Start date: 2022-03-22
• Primary completion: 2023-10-16
• Completion: 2023-10-16
• First posted: 2021-02-21
• Last updated: 2024-07-23
• Results posted: 2024-07-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study