Back to resultsEfficacy of Liraglutide Therapy in Patients With IPAA
Primary Purpose
Pouchitis, Irritable Pouch Syndrome
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Liraglutide Pen Injector
Placebo Pen Injector
Sponsored by
About this trial
This is an interventional treatment trial for Pouchitis
Eligibility Criteria
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.
Sites / Locations
- University of North Carolina
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Liraglutide then Placebo
Placebo then Liraglutide
Arm Description
Participants will be randomly assigned to 6-week Liraglutide treatment. Then after a 5-day washout, treatment will continue with 6 weeks of placebo.
Participants will be randomly assigned to 6-week placebo treatment. Then after a 5-day washout, treatment will continue with 6 weeks of Liraglutide.
Outcomes
Primary Outcome Measures
Change in Mean 7-Day Bowel Frequency By 30%
Percentage of patients with a 30% reduction of the mean 7-day bowel frequency at week 4 and week 10 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).
Secondary Outcome Measures
Change in the 7 Day Mean Number of Day and Night Bowel Frequency
The bowel frequency during the day and night will be recorded on a daily basis. Change in the number of the 7 days mean number of bowel movements during day (from getting up until bedtime) and during night (during sleep) comparing baseline to week 1, week 2, week 3 and week 4 during active treatment with liraglutide or placebo in period 1 or in period 2 (week 7, 8, 9 and 10).
Change in Clinical Modified Pouch Disease Activity Index (mPDAI) Score
The clinical mPDAI will be measured at baseline, week 4, and week 10. The clinical mPDAI is a composite score of stool frequency, presence of rectal bleeding, fecal urgency/abdominal cramps or fever. The clinical mPDAI score ranges from 0 to 6. Values < 3 are considered as remission, whereas symptoms ≥ 3 are considered as having active pouchitis.
Discontinuation of Liraglutide Therapy
Number of patients discontinuing Liraglutide therapy in treatment and placebo arm
Full Information
NCT ID
NCT04763564
First Posted
February 16, 2021
Last Updated
October 16, 2023
Sponsor
University of North Carolina, Chapel Hill
Collaborators
Novo Nordisk A/S
1. Study Identification
Unique Protocol Identification Number
NCT04763564
Brief Title
Efficacy of Liraglutide Therapy in Patients With IPAA
Official Title
Efficacy of Liraglutide Therapy in Patients With an Ileal -Pouch Anal Anastomosis (IPAA) and Chronic High Bowel Frequency
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
March 22, 2022 (Actual)
Primary Completion Date
October 16, 2023 (Actual)
Study Completion Date
October 16, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
Novo Nordisk A/S
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pouchitis, Irritable Pouch Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Model Description
Randomized, double-blind, 2-period, placebo-controlled, crossover proof of concept study.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Liraglutide then Placebo
Arm Type
Experimental
Arm Description
Participants will be randomly assigned to 6-week Liraglutide treatment. Then after a 5-day washout, treatment will continue with 6 weeks of placebo.
Arm Title
Placebo then Liraglutide
Arm Type
Experimental
Arm Description
Participants will be randomly assigned to 6-week placebo treatment. Then after a 5-day washout, treatment will continue with 6 weeks of Liraglutide.
Intervention Type
Drug
Intervention Name(s)
Liraglutide Pen Injector
Other Intervention Name(s)
Victoza
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo Pen Injector
Other Intervention Name(s)
Saline
Intervention Description
Matching placebo pens used to administer normal saline in the same fashion as for liraglutide
Primary Outcome Measure Information:
Title
Change in Mean 7-Day Bowel Frequency By 30%
Description
Percentage of patients with a 30% reduction of the mean 7-day bowel frequency at week 4 and week 10 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).
Time Frame
week 4, week 10
Secondary Outcome Measure Information:
Title
Change in the 7 Day Mean Number of Day and Night Bowel Frequency
Description
The bowel frequency during the day and night will be recorded on a daily basis. Change in the number of the 7 days mean number of bowel movements during day (from getting up until bedtime) and during night (during sleep) comparing baseline to week 1, week 2, week 3 and week 4 during active treatment with liraglutide or placebo in period 1 or in period 2 (week 7, 8, 9 and 10).
Time Frame
up to 10 weeks
Title
Change in Clinical Modified Pouch Disease Activity Index (mPDAI) Score
Description
The clinical mPDAI will be measured at baseline, week 4, and week 10. The clinical mPDAI is a composite score of stool frequency, presence of rectal bleeding, fecal urgency/abdominal cramps or fever. The clinical mPDAI score ranges from 0 to 6. Values < 3 are considered as remission, whereas symptoms ≥ 3 are considered as having active pouchitis.
Time Frame
up to 10 weeks
Title
Discontinuation of Liraglutide Therapy
Description
Number of patients discontinuing Liraglutide therapy in treatment and placebo arm
Time Frame
up to 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hans Herfarth, MD, PhD
Organizational Affiliation
University of North Carolina
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Deidentified individual data that supports the results will be shared beginning 3 to 36 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 the University of North Carolina [UNC].
IPD Sharing Time Frame
Beginning 3 months and ending 36 months following article publication.
IPD Sharing Access Criteria
Researchers who provide a methodologically sound proposal.
Learn more about this trial
Efficacy of Liraglutide Therapy in Patients With IPAA
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