PouchitisPhase 2NCT04763564
Efficacy of Liraglutide Therapy in Patients With IPAA
A Phase 2 study testing Liraglutide Pen Injector in people with Pouchitis and Irritable Pouch Syndrome, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pouchitis, Irritable Pouch Syndrome
- What is being tested?
- Liraglutide Pen Injector
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Mar 2022to 16 Oct 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina
Chapel Hill, North Carolina, 27599
About this study
Official title: Efficacy of Liraglutide Therapy in Patients With an Ileal -Pouch Anal Anastomosis (IPAA) and Chronic High Bowel Frequency
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.
Read the 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
- Being tested
- Liraglutide Pen Injector, Placebo Pen Injector
- Medical subject headings
- Pouchitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liraglutide Pen InjectorDrug
Also called Victoza
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.
Placebo Pen InjectorDrug
Also called Saline
Matching placebo pens used to administer normal saline in the same fashion as for liraglutide
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Liraglutide Pen Injector; Drug: Placebo Pen Injector |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Bowel frequency during the day and night was recorded on a daily basis. The 7-day mean number of bowel movements during the day (from getting up until bedtime) and during the night (during sleep) at baseline and at weeks 4 and 6 on liraglutide or placebo therapy is depicted.
Baseline, week 4 and week 6 (treatment period 1) and week 10 and week 12 (treatment period 2)
Measured: 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
Number of patients discontinuing Liraglutide therapy in treatment or placebo arm due to intolerance in treatment period 1 before week 6 or treatment period 2 before week 12
Measured: 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.
Mean percentage reduction of 7-day bowel frequency after 6 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 6 or treatment period 2 at week 12 vs baseline.
Measured: Baseline, week 6 (treatment period 1) and week 12 (treatment period 2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start22 Mar 2022
- Primary completion16 Oct 2023
- Study completion16 Oct 2023
Why it stopped: Due to an interruption in drug supply, the study was terminated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PouchitisStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, double-blind, 2-period, placebo-controlled, crossover proof of concept study.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Novo Nordisk A/S
- Responsible party
- Sponsor
- Investigators
- Hans Herfarth, MD, PhD, Principal investigator, University of North Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04763564
- Sponsor's protocol ID
- 20-3016
- Other IDs
- U1111-1252-6589
- Status last verified
- Oct 2023
- First submitted
- 16 Feb 2021
- Last updated
- 23 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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 \[UNC\].
Publications
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.
PubMed 38668926
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Liraglutide Therapy in Patients With an Ileal -Pouch Anal Anastomosis (IPAA) and Chronic High Bowel Frequency
- ClinicalTrials.gov ID
- NCT04763564
- Acronym / sponsor ID
- 20-3016
- Conditions
- Pouchitis, Irritable Pouch Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to an interruption in drug supply, the study was terminated
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Novo Nordisk A/S
- Study start
- 22 Mar 2022 (actual)
- Primary completion
- 16 Oct 2023 (actual)
- Study completion
- 16 Oct 2023 (actual)
- First posted
- 21 Feb 2021 (actual)
- Results
- Posted 23 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, double-blind, 2-period, placebo-controlled, crossover proof of concept study.
| Arm | Type | Receives |
|---|---|---|
| Liraglutide then Placebo | Experimental | Drug: Liraglutide Pen Injector, Drug: Placebo Pen InjectorParticipants will be randomly assigned to 6-week Liraglutide treatment. Then after a 5-day washout, treatment will continue with 6 weeks of placebo. |
| Placebo then Liraglutide | Experimental | Drug: Liraglutide Pen Injector, Drug: Placebo Pen InjectorParticipants will be randomly assigned to 6-week placebo treatment. Then after a 5-day washout, treatment will continue with 6 weeks of Liraglutide. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liraglutide Pen InjectorAlso: VictozaTreatment 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 | Liraglutide then Placebo, Placebo then Liraglutide |
| Placebo Pen InjectorAlso: SalineMatching placebo pens used to administer normal saline in the same fashion as for liraglutide | Drug | Liraglutide then Placebo, Placebo then Liraglutide |
Primary outcome
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 .
Time frame: Baseline, Week 4 (treatment period 1) and week 10 (treatment period 2)
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.
3 secondary outcomes
Change in the 7 Day Mean Number of Day and Night Bowel Frequency at Week 4 and 6 vs Baseline on Liraglutide vs Placebo
Time frame: 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
Time frame: 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.
Time frame: Baseline, week 6 (treatment period 1) and week 12 (treatment period 2)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 38668926Herfarth 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.
- Individual participant dataSharing planned: Yes. 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].
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hans Herfarth, MD, PhD principal investigator
University of North Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Liraglutide Pen Injector in people with Pouchitis and Irritable Pouch Syndrome, run by University of North Carolina, Chapel Hill at 1 site 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 3 inclusion and 18 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: stopped early, as of the sponsor's last update on 23 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 . (time frame: Baseline, Week 4 (treatment period 1) and week 10 (treatment period 2)). 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 NCT04763564, which also lists 1 linked publication.
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 23 Jul 2024.