Efficacy of Liraglutide Therapy in Patients With IPAA

NCT04763564 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 20-3016U1111-1252-6589
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pouchitis; Irritable Pouch Syndrome

Outcome Measures

Primary Outcomes (1)

• Mean % Reduction of Bowel Frequency in Percent of the Mean 7-day Bowel Frequency After 4 Weeks of Therapy on Liraglutide vs Placebo Compared to Baseline .

  Mean percentage reduction of 7-day bowel frequency after 4 weeks of therapy on Liraglutide vs placebo compared to baseline (baseline is defined as the mean 7-day bowel frequency in a 7-day period during the screening period before week 0). Due to the cross-over design, the outcome is reported depending on randomization in treatment period 1 at week 4 and treatment period 2 at week 10 vs baseline.

  Baseline, Week 4 (treatment period 1) and week 10 (treatment period 2)

Secondary Outcomes (3)

• Change in the 7 Day Mean Number of Day and Night Bowel Frequency at Week 4 and 6 vs Baseline on Liraglutide vs Placebo

  Baseline, Week 4 and week 6 (treatment period 1) and week 10 and week 12 (treatment period 2)

• Discontinuation of Therapy in Each Treatment Arm

  treatment period 1 before week 6 or treatment period 2 before week 12

• Mean % Reduction of Bowel Frequency in Percent of the Mean 7-day Bowel Frequency After 6 Weeks of Therapy on Liraglutide vs Placebo Compared to Baseline.

  Baseline, week 6 (treatment period 1) and week 12 (treatment period 2)

Study Arms (2)

Liraglutide then Placebo

EXPERIMENTAL

Participants will be randomly assigned to 6-week Liraglutide treatment. Then after a 5-day washout, treatment will continue with 6 weeks of placebo.

Drug: Liraglutide Pen Injector; Drug: Placebo Pen Injector

Placebo then Liraglutide

EXPERIMENTAL

Participants will be randomly assigned to 6-week placebo treatment. Then after a 5-day washout, treatment will continue with 6 weeks of Liraglutide.

Drug: Liraglutide Pen Injector; Drug: Placebo Pen Injector

Interventions

Liraglutide Pen Injector DRUG

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.

Also known as: Victoza

Liraglutide then Placebo; Placebo then Liraglutide

Placebo Pen Injector DRUG

Matching placebo pens used to administer normal saline in the same fashion as for liraglutide

Also known as: Saline

Liraglutide then Placebo; Placebo then Liraglutide

Eligibility Criteria

• Age: 18 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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• Herfarth H, Long MD, Hansen JJ, Anderson C, English E, Buse JB, Barnes EL. Efficacy and Safety of Liraglutide in Patients With an Ileal Pouch-Anal Anastomosis and Chronic High Bowel Frequency: A Placebo-Controlled, Crossover, Proof-of-Concept Study. Am J Gastroenterol. 2024 Sep 1;119(9):1935-1938. doi: 10.14309/ajg.0000000000002801. Epub 2024 Apr 12.

  PMID: 38668926 RESULT

MeSH Terms

Conditions

Pouchitis

Interventions

Liraglutide; Sodium Chloride

Condition Hierarchy (Ancestors)

Ileitis; Enteritis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Ileal Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Small cross-over proof of concept study. The findings need to be verified in a more extensive prospective randomized study.

Results Point of Contact

• Title: Hans Herfarth, MD, PhD
• Organization: University of North Carolina at Chapel Hill

hherf@med.unc.edu

9199666806

Study Officials

• Hans Herfarth, MD, PhD

  University of North Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, 2-period, placebo-controlled, crossover proof of concept study.

Study Record Dates

• First Submitted: February 16, 2021
• First Posted: February 21, 2021
• Study Start: March 22, 2022
• Primary Completion: October 16, 2023
• Study Completion: October 16, 2023
• Last Updated: July 23, 2024
• Results First Posted: July 23, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 36 months following article publication.
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

US (1)