{"protocolSection":{"identificationModule":{"nctId":"NCT04763564","orgStudyIdInfo":{"id":"20-3016"},"secondaryIdInfos":[{"id":"U1111-1252-6589","type":"OTHER","domain":"WHO Universal Trial Number"}],"organization":{"fullName":"University of North Carolina, Chapel Hill","class":"OTHER"},"briefTitle":"Efficacy of Liraglutide Therapy in Patients With IPAA","officialTitle":"Efficacy of Liraglutide Therapy in Patients With an Ileal -Pouch Anal Anastomosis (IPAA) and Chronic High Bowel Frequency"},"statusModule":{"statusVerifiedDate":"2023-10","overallStatus":"TERMINATED","whyStopped":"Due to an interruption in drug supply, the study was terminated","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2022-03-22","type":"ACTUAL"},"primaryCompletionDateStruct":{"date":"2023-10-16","type":"ACTUAL"},"completionDateStruct":{"date":"2023-10-16","type":"ACTUAL"},"studyFirstSubmitDate":"2021-02-16","studyFirstSubmitQcDate":"2021-02-16","studyFirstPostDateStruct":{"date":"2021-02-21","type":"ACTUAL"},"resultsFirstSubmitDate":"2024-06-04","resultsFirstSubmitQcDate":"2024-06-28","resultsFirstPostDateStruct":{"date":"2024-07-23","type":"ACTUAL"},"lastUpdateSubmitDate":"2024-06-28","lastUpdatePostDateStruct":{"date":"2024-07-23","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"SPONSOR"},"leadSponsor":{"name":"University of North Carolina, Chapel Hill","class":"OTHER"},"collaborators":[{"name":"Novo Nordisk A/S","class":"INDUSTRY"}]},"oversightModule":{"oversightHasDmc":false,"isFdaRegulatedDrug":true,"isFdaRegulatedDevice":false},"descriptionModule":{"briefSummary":"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.","detailedDescription":"Randomized, double-blind, 2-period, placebo- controlled, crossover proof of concept study.\n\nTen 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."},"conditionsModule":{"conditions":["Pouchitis","Irritable Pouch Syndrome"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE2"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"CROSSOVER","interventionModelDescription":"Randomized, double-blind, 2-period, placebo-controlled, crossover proof of concept study.","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"QUADRUPLE","whoMasked":["PARTICIPANT","CARE_PROVIDER","INVESTIGATOR","OUTCOMES_ASSESSOR"]}},"enrollmentInfo":{"count":8,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Liraglutide then Placebo","type":"EXPERIMENTAL","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.","interventionNames":["Drug: Liraglutide Pen Injector","Drug: Placebo Pen Injector"]},{"label":"Placebo then Liraglutide","type":"EXPERIMENTAL","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.","interventionNames":["Drug: Liraglutide Pen Injector","Drug: Placebo Pen Injector"]}],"interventions":[{"type":"DRUG","name":"Liraglutide Pen Injector","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.","armGroupLabels":["Liraglutide then Placebo","Placebo then Liraglutide"],"otherNames":["Victoza"]},{"type":"DRUG","name":"Placebo Pen Injector","description":"Matching placebo pens used to administer normal saline in the same fashion as for liraglutide","armGroupLabels":["Liraglutide then Placebo","Placebo then Liraglutide"],"otherNames":["Saline"]}]},"outcomesModule":{"primaryOutcomes":[{"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 .","description":"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).\n\nDue 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.","timeFrame":"Baseline, Week 4 (treatment period 1) and week 10 (treatment period 2)"}],"secondaryOutcomes":[{"measure":"Change in the 7 Day Mean Number of Day and Night Bowel Frequency at Week 4 and 6 vs Baseline on Liraglutide vs Placebo","description":"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.\n\nBaseline, week 4 and week 6 (treatment period 1) and week 10 and week 12 (treatment period 2)","timeFrame":"Baseline, Week 4 and week 6 (treatment period 1) and week 10 and week 12 (treatment period 2)"},{"measure":"Discontinuation of Therapy in Each Treatment Arm","description":"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","timeFrame":"treatment period 1 before week 6 or treatment period 2 before week 12"},{"measure":"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.","description":"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).\n\nDue 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.","timeFrame":"Baseline, week 6 (treatment period 1) and week 12 (treatment period 2)"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Informed consent will be obtained before any trial-related procedures\n* Age \\> 18 years\n* 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\n\nExclusion Criteria:\n\n* Significant pouch inflammation defined as an endoscopic pouch disease activity index (PDAI ) ≥ 4\n* Known stricture of the ileo-anal anastomosis or afferent limb stricture\n* New onset of high bowel frequency in the setting of acute pouchitis\n* IPAA since \\< 6 months\n* Known Clostridium difficile pouchitis\n* Known clinically significant chronic nausea and/or vomiting in the past\n* Known type 1 or type 2 diabetes\n* History of or active neoplasia\n* Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2\n* Renal impairment defined as glomerular filtration rate (glomerular filtration rate \\< 30)\n* 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)\n* New York Heart Association class 3 or greater heart failure or recent (within 6 months) cardiovascular event\n* Prior history of pancreatitis\n* Prior treatment with a GLP-1receptor agonist\n* Known hypersensitivity to liraglutide or any product components\n* 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.\n* Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days before screening.\n* Any disorder, which in the investigator's opinion might jeopardize patient's safety or compliance with the protocol.","healthyVolunteers":false,"sex":"ALL","minimumAge":"18 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Hans Herfarth, MD, PhD","affiliation":"University of North Carolina","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"University of North Carolina","city":"Chapel Hill","state":"North Carolina","zip":"27599","country":"United States","geoPoint":{"lat":35.9132,"lon":-79.05584}}]},"referencesModule":{"references":[{"pmid":"38668926","type":"RESULT","citation":"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."}]},"ipdSharingStatementModule":{"ipdSharing":"YES","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\\].","infoTypes":["STUDY_PROTOCOL","SAP","ICF","ANALYTIC_CODE"],"timeFrame":"Beginning 3 months and ending 36 months following article publication.","accessCriteria":"Researchers who provide a methodologically sound proposal."}},"resultsSection":{"participantFlowModule":{"recruitmentDetails":"Due to an interruption in drug supply, the study was terminated after 8 of 10 patients were included.","groups":[{"id":"FG000","title":"Liraglutide Then Placebo","description":"Participants first received Liraglutide treatment for 6 weeks. After a 5-day washout, they then received Placebo treatment for 6 weeks.\n\nLiraglutide 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.\n\nPlacebo Pen Injector: Matching placebo pens used to administer normal saline in the same fashion as for liraglutide"},{"id":"FG001","title":"Placebo Then Liraglutide","description":"Participants first received Placebo treatment for 6 weeks. After a 5-day washout, they then received Liraglutide treatment for 6 weeks.\n\nLiraglutide 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.\n\nPlacebo Pen Injector: Matching placebo pens used to administer normal saline in the same fashion as for liraglutide"}],"periods":[{"title":"First Intervention","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"3"},{"groupId":"FG001","numSubjects":"5"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"3"},{"groupId":"FG001","numSubjects":"5"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"}]}]},{"title":"Washout","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"3"},{"groupId":"FG001","numSubjects":"5"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"3"},{"groupId":"FG001","numSubjects":"5"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"}]}]},{"title":"Second Intervention","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"3"},{"groupId":"FG001","numSubjects":"5"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"3"},{"groupId":"FG001","numSubjects":"5"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Liraglutide Then Placebo","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.\n\nLiraglutide 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.\n\nPlacebo Pen Injector: Matching placebo pens used to administer normal saline in the same fashion as for liraglutide"},{"id":"BG001","title":"Placebo Then Liraglutide","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.\n\nLiraglutide 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.\n\nPlacebo Pen Injector: Matching placebo pens used to administer normal saline in the same fashion as for liraglutide"},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"3"},{"groupId":"BG001","value":"5"},{"groupId":"BG002","value":"8"}]}],"measures":[{"title":"Age, Categorical","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"<=18 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Between 18 and 65 years","measurements":[{"groupId":"BG000","value":"3"},{"groupId":"BG001","value":"5"},{"groupId":"BG002","value":"8"}]},{"title":">=65 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]}]}]},{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"FULL_RANGE","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"49","lowerLimit":"42","upperLimit":"55"},{"groupId":"BG001","value":"52","lowerLimit":"44","upperLimit":"65"},{"groupId":"BG002","value":"51","lowerLimit":"42","upperLimit":"65"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"2"},{"groupId":"BG001","value":"4"},{"groupId":"BG002","value":"6"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"1"},{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"2"}]}]}]},{"title":"Race (NIH/OMB)","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"American Indian or Alaska Native","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Asian","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Native Hawaiian or Other Pacific Islander","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Black or African American","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"White","measurements":[{"groupId":"BG000","value":"3"},{"groupId":"BG001","value":"5"},{"groupId":"BG002","value":"8"}]},{"title":"More than one race","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Unknown or Not Reported","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]}]}]},{"title":"Region of Enrollment","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"title":"United States","categories":[{"measurements":[{"groupId":"BG000","value":"3"},{"groupId":"BG001","value":"5"},{"groupId":"BG002","value":"8"}]}]}]},{"title":"Daily bowel frequency","description":"Data collected using participant diaries.","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"bowel movements/day","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"10.9","spread":"2.1"},{"groupId":"BG001","value":"12.8","spread":"2.0"},{"groupId":"BG002","value":"12.1","spread":"3.1"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"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 .","description":"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).\n\nDue 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.","populationDescription":"Analyses were performed according to treatment with Liraglutide vs Placebo (not according to arm/sequence).","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"percentage reduction of bowel frequency","timeFrame":"Baseline, Week 4 (treatment period 1) and week 10 (treatment period 2)","groups":[{"id":"OG000","title":"Liraglutide","description":"6-week Liraglutide treatment. 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."},{"id":"OG001","title":"Placebo","description":"6-week placebo treatment. Placebo Pen Injector: Matching placebo pens used to administer normal saline in the same fashion as for liraglutide"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"},{"groupId":"OG001","value":"8"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"36.3","spread":"19.8"},{"groupId":"OG001","value":"17.3","spread":"15.7"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"The 2 treatment modalities, Liraglutide and Placebo, were compared. A repeated-measures mixed model was fitted to the data, with treatment (liraglutide or placebo), period, and treatment sequence as fixed effects and the repeated measures within the subject as a random effect.","nonInferiorityType":"SUPERIORITY","pValue":"<0.03","pValueComment":"A priori threshold for significance was \\< 0.05. Significance level liraglutide vs. placebo in percent reduction of bowel frequency at week 4 vs. baseline.","statisticalMethod":"Mixed Models Analysis"}]},{"type":"SECONDARY","title":"Change in the 7 Day Mean Number of Day and Night Bowel Frequency at Week 4 and 6 vs Baseline on Liraglutide vs Placebo","description":"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.\n\nBaseline, week 4 and week 6 (treatment period 1) and week 10 and week 12 (treatment period 2)","populationDescription":"Analyses were performed according to treatment with Liraglutide vs Placebo (not according to arm/sequence).","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"Bowel movements / day or night","timeFrame":"Baseline, Week 4 and week 6 (treatment period 1) and week 10 and week 12 (treatment period 2)","groups":[{"id":"OG000","title":"Liraglutide","description":"6-week Liraglutide treatment. 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."},{"id":"OG001","title":"Placebo","description":"6-week placebo treatment. Placebo Pen Injector: Matching placebo pens used to administer normal saline in the same fashion as for liraglutide"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"},{"groupId":"OG001","value":"8"}]}],"classes":[{"title":"Baseline Bowel Frequency Day","categories":[{"measurements":[{"groupId":"OG000","value":"8.8","spread":"2.3"},{"groupId":"OG001","value":"8.8","spread":"2.3"}]}]},{"title":"Baseline Bowel Frequency Night","categories":[{"measurements":[{"groupId":"OG000","value":"3.3","spread":"1.7"},{"groupId":"OG001","value":"8.8","spread":"2.3"}]}]},{"title":"Week 4 Day","categories":[{"measurements":[{"groupId":"OG000","value":"5.3","spread":"2.2"},{"groupId":"OG001","value":"6.9","spread":"2.2"}]}]},{"title":"Week 4 Night","categories":[{"measurements":[{"groupId":"OG000","value":"2.3","spread":"1.1"},{"groupId":"OG001","value":"3.1","spread":"1.6"}]}]},{"title":"Week 6 Day","categories":[{"measurements":[{"groupId":"OG000","value":"5.4","spread":"1.9"},{"groupId":"OG001","value":"7.0","spread":"2.0"}]}]},{"title":"Week 6 Night Placebo week 6","categories":[{"measurements":[{"groupId":"OG000","value":"2.1","spread":"1.0"},{"groupId":"OG001","value":"3.1","spread":"1.8"}]}]}]},{"type":"SECONDARY","title":"Discontinuation of Therapy in Each Treatment Arm","description":"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","populationDescription":"Analyses were performed according to treatment with Liraglutide vs Placebo (not according to arm/sequence).","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"treatment period 1 before week 6 or treatment period 2 before week 12","groups":[{"id":"OG000","title":"Liraglutide","description":"6-week Liraglutide treatment.\n\nLiraglutide 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."},{"id":"OG001","title":"Placebo","description":"6-week placebo treatment.\n\nPlacebo Pen Injector: Matching placebo pens used to administer normal saline in the same fashion as for liraglutide"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"},{"groupId":"OG001","value":"8"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"}]}]}]},{"type":"SECONDARY","title":"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.","description":"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).\n\nDue 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.","populationDescription":"Analyses were performed according to treatment with Liraglutide vs Placebo (not according to arm/sequence).","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"Percent reduction of bowel frequency","timeFrame":"Baseline, week 6 (treatment period 1) and week 12 (treatment period 2)","groups":[{"id":"OG000","title":"Liraglutide","description":"Mean reduction of bowel frequency in percent of the mean 7-day bowel frequency after 6 weeks of therapy on Liraglutide compared to baseline"},{"id":"OG001","title":"Placebo","description":"Mean reduction of bowel frequency in percent of the mean 7-day bowel frequency after 6 weeks of therapy on Placebo compared to baseline"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"},{"groupId":"OG001","value":"8"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"36.8","spread":"18.7"},{"groupId":"OG001","value":"15.7","spread":"5.3"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"The 2 treatment modalities, Liraglutide and Placebo, were compared. A repeated-measures mixed model was fitted to the data, with treatment (liraglutide or placebo), period, and treatment sequence as fixed effects and the repeated measures within the subject as a random effect.","nonInferiorityType":"SUPERIORITY","pValue":"0.01","statisticalMethod":"Mixed Models Analysis"}]}]},"adverseEventsModule":{"frequencyThreshold":"0","timeFrame":"The adverse events were collected from each study participant from the screening visit until the last study visit at week 14","eventGroups":[{"id":"EG000","title":"Liraglutide","description":"6-week Liraglutide treatment.\n\nLiraglutide 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.","deathsNumAffected":0,"deathsNumAtRisk":8,"seriousNumAffected":0,"seriousNumAtRisk":8,"otherNumAffected":8,"otherNumAtRisk":8},{"id":"EG001","title":"Placebo","description":"6-week placebo treatment.\n\nPlacebo Pen Injector: Matching placebo pens used to administer normal saline in the same fashion as for liraglutide","deathsNumAffected":0,"deathsNumAtRisk":8,"seriousNumAffected":0,"seriousNumAtRisk":8,"otherNumAffected":6,"otherNumAtRisk":8}],"otherEvents":[{"term":"Nausea","organSystem":"Gastrointestinal disorders","sourceVocabulary":"MEDRA","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":5,"numAffected":5,"numAtRisk":8},{"groupId":"EG001","numEvents":2,"numAffected":2,"numAtRisk":8}]},{"term":"Diarrhea (intermittent)","organSystem":"Gastrointestinal disorders","sourceVocabulary":"MEDRA","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":4,"numAffected":4,"numAtRisk":8},{"groupId":"EG001","numEvents":2,"numAffected":2,"numAtRisk":8}]},{"term":"Headache","organSystem":"Nervous system disorders","sourceVocabulary":"MEDRA","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":4,"numAffected":4,"numAtRisk":8},{"groupId":"EG001","numEvents":2,"numAffected":2,"numAtRisk":8}]},{"term":"Fatigue","organSystem":"General disorders","sourceVocabulary":"MEDRA","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":2,"numAffected":2,"numAtRisk":8},{"groupId":"EG001","numEvents":1,"numAffected":1,"numAtRisk":8}]},{"term":"Abdominal pain","organSystem":"Gastrointestinal disorders","sourceVocabulary":"MEDRA","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":2,"numAffected":2,"numAtRisk":8},{"groupId":"EG001","numEvents":1,"numAffected":1,"numAtRisk":8}]},{"term":"Acid reflux","organSystem":"Gastrointestinal disorders","sourceVocabulary":"MEDRA","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":8},{"groupId":"EG001","numEvents":1,"numAffected":1,"numAtRisk":8}]},{"term":"Hypoglycemic episode","organSystem":"Metabolism and nutrition disorders","sourceVocabulary":"MEDRA","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":8},{"groupId":"EG001","numEvents":2,"numAffected":2,"numAtRisk":8}]},{"term":"Urinary tract infection","organSystem":"Renal and urinary disorders","sourceVocabulary":"MEDRA","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":8},{"groupId":"EG001","numEvents":1,"numAffected":1,"numAtRisk":8}]},{"term":"Joint pain","organSystem":"Musculoskeletal and connective tissue disorders","sourceVocabulary":"MEDRA","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":8},{"groupId":"EG001","numEvents":1,"numAffected":1,"numAtRisk":8}]},{"term":"Hair loss","organSystem":"General disorders","sourceVocabulary":"MEDRA","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":8},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":8}]},{"term":"Chest tightness","organSystem":"General disorders","sourceVocabulary":"MEDRA","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":8},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":8}]},{"term":"Index finger n numbness","organSystem":"Nervous system disorders","sourceVocabulary":"MEDRA","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":8},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":8}]},{"term":"Rash","organSystem":"Skin and subcutaneous tissue disorders","sourceVocabulary":"MEDRA","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":8},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":8}]},{"term":"Hiccup","organSystem":"Gastrointestinal disorders","sourceVocabulary":"MEDRA","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":8},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":8}]}]},"moreInfoModule":{"limitationsAndCaveats":{"description":"Small cross-over proof of concept study. The findings need to be verified in a more extensive prospective randomized study."},"certainAgreement":{"piSponsorEmployee":true,"restrictiveAgreement":false},"pointOfContact":{"title":"Hans Herfarth, MD, PhD","organization":"University of North Carolina at Chapel Hill","email":"hherf@med.unc.edu","phone":"9199666806"}}},"documentSection":{"largeDocumentModule":{"largeDocs":[{"typeAbbrev":"Prot_SAP","hasProtocol":true,"hasSap":true,"hasIcf":false,"label":"Study Protocol and Statistical Analysis Plan","date":"2022-03-22","uploadDate":"2024-04-15T15:21","filename":"Prot_SAP_000.pdf","size":1128424}]}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-09","submissionTracking":{"firstMcpInfo":{"postDateStruct":{"date":"2024-06-28","type":"ACTUAL"}}}},"conditionBrowseModule":{"meshes":[{"id":"D019449","term":"Pouchitis"}],"ancestors":[{"id":"D007079","term":"Ileitis"},{"id":"D004751","term":"Enteritis"},{"id":"D005759","term":"Gastroenteritis"},{"id":"D005767","term":"Gastrointestinal Diseases"},{"id":"D004066","term":"Digestive System Diseases"},{"id":"D007410","term":"Intestinal Diseases"},{"id":"D007077","term":"Ileal Diseases"}]},"interventionBrowseModule":{"meshes":[{"id":"D000069450","term":"Liraglutide"},{"id":"D012965","term":"Sodium Chloride"}],"ancestors":[{"id":"D052216","term":"Glucagon-Like Peptide 1"},{"id":"D004763","term":"Glucagon-Like Peptides"},{"id":"D052336","term":"Proglucagon"},{"id":"D005768","term":"Gastrointestinal Hormones"},{"id":"D006728","term":"Hormones"},{"id":"D006730","term":"Hormones, Hormone Substitutes, and Hormone Antagonists"},{"id":"D002712","term":"Chlorides"},{"id":"D006851","term":"Hydrochloric Acid"},{"id":"D017606","term":"Chlorine Compounds"},{"id":"D007287","term":"Inorganic Chemicals"},{"id":"D017670","term":"Sodium Compounds"}]}},"hasResults":true}