{"protocolSection":{"identificationModule":{"nctId":"NCT02777073","orgStudyIdInfo":{"id":"1974"},"organization":{"fullName":"University at Buffalo","class":"OTHER"},"briefTitle":"Effects of Single Doses of Liraglutide and Dapagliflozin on Ketogenesis in Type 1 Diabetes","officialTitle":"Effects of Single Doses of Liraglutide and Dapagliflozin on Hyperglycemia and Ketogenesis in Type 1 Diabetes","acronym":"1974"},"statusModule":{"statusVerifiedDate":"2024-02","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2016-03-01","type":"ACTUAL"},"primaryCompletionDateStruct":{"date":"2016-12-01","type":"ACTUAL"},"completionDateStruct":{"date":"2016-12-31","type":"ACTUAL"},"studyFirstSubmitDate":"2015-12-01","studyFirstSubmitQcDate":"2016-05-16","studyFirstPostDateStruct":{"date":"2016-05-19","type":"ESTIMATED"},"resultsFirstSubmitDate":"2022-10-31","resultsFirstSubmitQcDate":"2024-02-03","resultsFirstPostDateStruct":{"date":"2024-02-29","type":"ACTUAL"},"lastUpdateSubmitDate":"2024-02-03","lastUpdatePostDateStruct":{"date":"2024-02-29","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"PRINCIPAL_INVESTIGATOR","investigatorFullName":"Paresh Dandona","investigatorTitle":"Distinguished Professor","investigatorAffiliation":"University at Buffalo"},"leadSponsor":{"name":"University at Buffalo","class":"OTHER"}},"oversightModule":{"oversightHasDmc":true},"descriptionModule":{"briefSummary":"1. To compare levels of ketone bodies (beta-hydroxybutyrate and acetoacetate) in plasma and urine following a single dose treatment of either liraglutide 1.8mg, dapagliflozin 10mg or placebo in insulinopenic state.\n2. To compare plasma levels of free fatty acid, glucagon, hs-CRP, Ll-6 and IL-1 before and after administration of liraglutide/placebo.","detailedDescription":"Diabetic ketoacidosis is an important cause of mortality and morbidity in type 1 patients. The decreased ratio of insulin to glucagon in insulin deficient subjects promotes ketogenesis. In patients with type 1 diabetes, the suppressive effect of hyperglycemia and the paracrine inhibitory effect of insulin and GABA from the β cell on α cell are absent. Thus, plasma glucagon concentrations are elevated and in combination with insulin deficiency, lead to lipolysis, increased plasma FFA concentrations and an increased fatty acid supply to the liver. Thus, both fatty acid oxidation and ketogenesis are enhanced.\n\nOur recent work has shown that liraglutide, a GLP 1 agonist, improves glycemic control and reduces glycemic excursions in patients with type 1 diabetes within a few days of the initiation of treatment.\n\nWith this background, the investigators hypothesize that suppression of glucagon with liraglutide in patients with type 1 diabetes may protect them from lipolysis, increased bio-availability of FFAs, ketogenesis and ketoacidosis.\n\nIt is essential to investigate this area further as there are no prior studies that have investigated the acute effects of liraglutide on FFAs or ketogenesis. This study will be the first randomized controlled prospective study investigating the effect of liraglutide on ketogenesis. Also, it would be important to measure the mediators of inflammation at the same time to investigate whether there is a concomitant changes of inflammatory factors in parallel with the lipolysis and ketogenesis.\n\nAfter the screening visit, subjects who meet the inclusion and exclusion criteria will be randomized to receive a single dose of either liraglutide, dapagliflozin or placebo and will be monitored for a total of 8 hours."},"conditionsModule":{"conditions":["Type 1 Diabetes"],"keywords":["Diabetic ketoacidosis","Insulin","Type 1 Diabetes","glucose (sugar) control"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["NA"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"SINGLE","whoMasked":["PARTICIPANT"]}},"enrollmentInfo":{"count":43,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"liraglutide 1.8 mg","type":"ACTIVE_COMPARATOR","description":"single dose of Victoza ( liraglutide) 1.8 mg","interventionNames":["Drug: Victoza"]},{"label":"Placebo","type":"PLACEBO_COMPARATOR","description":"Single dose of placebo","interventionNames":["Drug: Placebo"]},{"label":"Dapagliflozin","type":"ACTIVE_COMPARATOR","description":"Single dose of Dapagliflozin 10 mg oral tablet","interventionNames":["Drug: Dapagliflozin 10mg Tab"]}],"interventions":[{"type":"DRUG","name":"Victoza","description":"Single dose of Liraglutide","armGroupLabels":["liraglutide 1.8 mg"],"otherNames":["Liraglutide"]},{"type":"DRUG","name":"Placebo","description":"Single dose of generic placebo","armGroupLabels":["Placebo"]},{"type":"DRUG","name":"Dapagliflozin 10mg Tab","description":"single dose of 10 mg dapagliflozin","armGroupLabels":["Dapagliflozin"],"otherNames":["Dapagliflozin"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Difference in Ketone Bodies Formation After Single Dose of Liraglutide and Dapagliflozin","description":"To compare levels of ketone bodies beta-hydroxybutyrate in plasma following a single dose treatment of either liraglutide 1.8mg,dapagliflozin 10mg or placebo in insulinopenic state.","timeFrame":"8 hours"}],"secondaryOutcomes":[{"measure":"Change in Glucagon Levels.","description":"This secondary endpoint compares change in glucagon concentrations (in pg/ml) from baseline at 8 hours following liraglutide and dapagliflozin compared to placebo","timeFrame":"8 hours"},{"measure":"Change in Free Fatty Acid (FFA) Concentrations","description":"This secondary endpoint compares the change in FFA concentrations (mM) from baseline at 8 hours following liraglutide and dapagliflozin compared to placebo","timeFrame":"8 hours"},{"measure":"Change in Ghrelin Concentrations","description":"This secondary endpoint compares the change in ghrelin concentrations (pg/ml) from baseline at 8 hours following liraglutide and dapagliflozin compared to placebo","timeFrame":"8 Hours"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n1. Type 1 Diabetes on continuous subcutaneous insulin infusion (CSII, also known as insulin pump).\n2. Undetectable c peptide (c-peptide \\< 0.1 ng/ml).\n3. HbA1c of less than or equal to 8.5%.\n4. Age 18-75 inclusive\n\nExclusion Criteria:\n\n1. Type 1 diabetes for less than 12 months\n2. Coronary event/ procedure (MI, Unstable angina, CABG, PCI) in the last four weeks\n3. Hepatic disease (Transaminase \\> 3 times normal) or Cirrhosis\n4. Renal impairment (serum eGFR \\<30ml/min/1.73m2)\n5. HIV or Hepatitis B or C positive status\n6. History of pancreatitis, i.e., history of gallstones, alcohol abuse and hypertriglyceridemia\n7. Pregnancy\n8. Inability to give informed consent\n9. History of Gastroparesis\n10. Personal or Family History of medullary thyroid carcinoma or MEN 2 syndrome\n11. Alcoholism\n12. Hypertriglyceridemia (\\>500 mg/dl).\n13. Those with history of bladder cancer , diabetic ketoacidosis","healthyVolunteers":false,"sex":"ALL","minimumAge":"18 Years","maximumAge":"75 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"locations":[{"facility":"ECMC Ambulatory Center, 3rd Floor","city":"Buffalo","state":"New York","zip":"14215","country":"United States","geoPoint":{"lat":42.88645,"lon":-78.87837}}]},"ipdSharingStatementModule":{"ipdSharing":"NO"}},"resultsSection":{"participantFlowModule":{"groups":[{"id":"FG000","title":"Liraglutide 1.8 mg","description":"single dose of Victoza ( liraglutide) 1.8 mg\n\nVictoza: Single dose of Liraglutide"},{"id":"FG001","title":"Dapagliflozin 10","description":"single dose of Farxiga ( dapagliflozin) 10 mg\n\nFarxiga: Single dose of dapagliflozin"},{"id":"FG002","title":"Placebo","description":"Single dose of placebo\n\nPlacebo: Single dose of generic placebo"}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"13"},{"groupId":"FG001","numSubjects":"17"},{"groupId":"FG002","numSubjects":"13"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"13"},{"groupId":"FG001","numSubjects":"17"},{"groupId":"FG002","numSubjects":"13"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Liraglutide 1.8 mg","description":"single dose of Victoza ( liraglutide) 1.8 mg\n\nVictoza: Single dose of Liraglutide"},{"id":"BG001","title":"Dapagliflozin 10","description":"single dose of Farxiga ( dapagliflozin) 10 mg\n\nFarxiga: Single dose of dapagliflozin"},{"id":"BG002","title":"Placebo","description":"Single dose of placebo\n\nPlacebo: Single dose of generic placebo"},{"id":"BG003","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"13"},{"groupId":"BG001","value":"17"},{"groupId":"BG002","value":"13"},{"groupId":"BG003","value":"43"}]}],"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"},{"groupId":"BG003","value":"0"}]},{"title":"Between 18 and 65 years","measurements":[{"groupId":"BG000","value":"13"},{"groupId":"BG001","value":"17"},{"groupId":"BG002","value":"13"},{"groupId":"BG003","value":"43"}]},{"title":">=65 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"0"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"7"},{"groupId":"BG001","value":"10"},{"groupId":"BG002","value":"7"},{"groupId":"BG003","value":"24"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"6"},{"groupId":"BG001","value":"7"},{"groupId":"BG002","value":"6"},{"groupId":"BG003","value":"19"}]}]}]},{"title":"Ethnicity (NIH/OMB)","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Hispanic or Latino","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"0"}]},{"title":"Not Hispanic or Latino","measurements":[{"groupId":"BG000","value":"13"},{"groupId":"BG001","value":"17"},{"groupId":"BG002","value":"13"},{"groupId":"BG003","value":"43"}]},{"title":"Unknown or Not Reported","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"0"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Difference in Ketone Bodies Formation After Single Dose of Liraglutide and Dapagliflozin","description":"To compare levels of ketone bodies beta-hydroxybutyrate in plasma following a single dose treatment of either liraglutide 1.8mg,dapagliflozin 10mg or placebo in insulinopenic state.","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Error","unitOfMeasure":"mM","timeFrame":"8 hours","groups":[{"id":"OG000","title":"Liraglutide 1.8 mg","description":"single dose of Victoza ( liraglutide) 1.8 mg\n\nVictoza: Single dose of Liraglutide"},{"id":"OG001","title":"Placebo","description":"Single dose of placebo\n\nPlacebo: Single dose of generic placebo"},{"id":"OG002","title":"Dapagliflozin","description":"Single dose of dapagliflozin 10 mg"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"13"},{"groupId":"OG001","value":"13"},{"groupId":"OG002","value":"17"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"0.08","spread":"0.05"},{"groupId":"OG001","value":"0.25","spread":"0.05"},{"groupId":"OG002","value":"0.21","spread":"0.05"}]}]}]},{"type":"SECONDARY","title":"Change in Glucagon Levels.","description":"This secondary endpoint compares change in glucagon concentrations (in pg/ml) from baseline at 8 hours following liraglutide and dapagliflozin compared to placebo","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Error","unitOfMeasure":"pg/mL","timeFrame":"8 hours","groups":[{"id":"OG000","title":"Liraglutide 1.8 mg","description":"single dose of Victoza ( liraglutide) 1.8 mg\n\nVictoza: Single dose of Liraglutide"},{"id":"OG001","title":"Placebo","description":"Single dose of placebo\n\nPlacebo: Single dose of generic placebo"},{"id":"OG002","title":"Dapagliflozin","description":"Single dose of dapagliflozin 10mg"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"13"},{"groupId":"OG001","value":"13"},{"groupId":"OG002","value":"17"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-19","spread":"14"},{"groupId":"OG001","value":"1","spread":"6"},{"groupId":"OG002","value":"-15","spread":"5"}]}]}]},{"type":"SECONDARY","title":"Change in Free Fatty Acid (FFA) Concentrations","description":"This secondary endpoint compares the change in FFA concentrations (mM) from baseline at 8 hours following liraglutide and dapagliflozin compared to placebo","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Error","unitOfMeasure":"mM","timeFrame":"8 hours","groups":[{"id":"OG000","title":"Liraglutide 1.8 mg","description":"single dose of Victoza ( liraglutide) 1.8 mg\n\nVictoza: Single dose of Liraglutide"},{"id":"OG001","title":"Placebo","description":"Single dose of placebo\n\nPlacebo: Single dose of generic placebo"},{"id":"OG002","title":"Dapagliflozin","description":"Single dose of dapagliflozin 10mg"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"13"},{"groupId":"OG001","value":"13"},{"groupId":"OG002","value":"17"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"0.1","spread":"0.06"},{"groupId":"OG001","value":"0.17","spread":"0.06"},{"groupId":"OG002","value":"0.11","spread":".06"}]}]}]},{"type":"SECONDARY","title":"Change in Ghrelin Concentrations","description":"This secondary endpoint compares the change in ghrelin concentrations (pg/ml) from baseline at 8 hours following liraglutide and dapagliflozin compared to placebo","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Error","unitOfMeasure":"pg/mL","timeFrame":"8 Hours","groups":[{"id":"OG000","title":"Liraglutide 1.8 mg","description":"single dose of Victoza ( liraglutide) 1.8 mg\n\nVictoza: Single dose of Liraglutide"},{"id":"OG001","title":"Placebo","description":"Single dose of placebo\n\nPlacebo: Single dose of generic placebo"},{"id":"OG002","title":"Dapagliflozin","description":"Single dose of dapagliflozin 10mg"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"13"},{"groupId":"OG001","value":"13"},{"groupId":"OG002","value":"17"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-32","spread":"28"},{"groupId":"OG001","value":"66","spread":"29"},{"groupId":"OG002","value":"32","spread":"26"}]}]}]}]},"adverseEventsModule":{"frequencyThreshold":"5","timeFrame":"throughout patient participation period of 8hr and up to 72 hrs follow-up after the dose administration","description":"No adverse events occurred during the study.","eventGroups":[{"id":"EG000","title":"Liraglutide 1.8 mg","description":"single dose of Victoza ( liraglutide) 1.8 mg\n\nVictoza: Single dose of Liraglutide","deathsNumAffected":0,"deathsNumAtRisk":13,"seriousNumAffected":0,"seriousNumAtRisk":13,"otherNumAffected":0,"otherNumAtRisk":13},{"id":"EG001","title":"Dapagliflozin","description":"Single dose of dapagliflozin 10 mg","deathsNumAffected":0,"deathsNumAtRisk":17,"seriousNumAffected":0,"seriousNumAtRisk":17,"otherNumAffected":0,"otherNumAtRisk":17},{"id":"EG002","title":"Placebo","description":"Single dose of placebo\n\nPlacebo: Single dose of generic placebo","deathsNumAffected":0,"deathsNumAtRisk":13,"seriousNumAffected":0,"seriousNumAtRisk":13,"otherNumAffected":0,"otherNumAtRisk":13}]},"moreInfoModule":{"certainAgreement":{"piSponsorEmployee":true},"pointOfContact":{"title":"Paresh Dandona","organization":"State University of NY at Buffalo","email":"dandona@buffalo.edu","phone":"7165351850"}}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-09"},"conditionBrowseModule":{"meshes":[{"id":"D003922","term":"Diabetes Mellitus, Type 1"},{"id":"D016883","term":"Diabetic Ketoacidosis"},{"id":"D007333","term":"Insulin Resistance"}],"ancestors":[{"id":"D003920","term":"Diabetes Mellitus"},{"id":"D044882","term":"Glucose Metabolism Disorders"},{"id":"D008659","term":"Metabolic Diseases"},{"id":"D009750","term":"Nutritional and Metabolic Diseases"},{"id":"D004700","term":"Endocrine System Diseases"},{"id":"D001327","term":"Autoimmune Diseases"},{"id":"D007154","term":"Immune System Diseases"},{"id":"D007662","term":"Ketosis"},{"id":"D000138","term":"Acidosis"},{"id":"D000137","term":"Acid-Base Imbalance"},{"id":"D048909","term":"Diabetes Complications"},{"id":"D006946","term":"Hyperinsulinism"}]},"interventionBrowseModule":{"meshes":[{"id":"D000069450","term":"Liraglutide"},{"id":"C529054","term":"dapagliflozin"}],"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"}]}},"hasResults":true}