Efficacy of Liraglutide Therapy in Patients With IPAA

University of North Carolina (UNC)

Status and phase

Terminated

Phase 2

Conditions

Irritable Pouch Syndrome

Pouchitis

Treatments

Drug: Liraglutide Pen Injector

Drug: Placebo Pen Injector

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT04763564

U1111-1252-6589 (Other Identifier)

20-3016

Details and patient eligibility

About

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.

Full 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.

Enrollment

8 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Informed consent will be obtained before any trial-related procedures
Age > 18 years
Patients with IPAA and 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

Exclusion criteria

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
IPAA since < 6 months
Known Clostridium difficile pouchitis
Known clinically significant chronic nausea and/or vomiting in the past
Known type 1 or type 2 diabetes
History of or active neoplasia
Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2
Renal impairment defined as glomerular filtration rate (glomerular filtration rate < 30)
Clinically significant decompensated liver disease defined as elevation of aspartate aminotransferase , alanine transaminase or bilirubin > 2-fold the upper limits of normal (Primary Sclerosing Cholangitis with liver function tests (LFT's) <1.5 upper limits of normal can be included)
New York Heart Association class 3 or greater heart failure or recent (within 6 months) cardiovascular event
Prior history of pancreatitis
Prior treatment with a GLP-1receptor agonist
Known hypersensitivity to liraglutide or any product components
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 patient's safety or compliance with the protocol.