Nctid:
NCT06229678
Payload:
{"hasResults"=>false, "derivedSection"=>{"miscInfoModule"=>{"versionHolder"=>"2024-12-20"}, "conditionBrowseModule"=>{"meshes"=>[{"id"=>"D006333", "term"=>"Heart Failure"}], "ancestors"=>[{"id"=>"D006331", "term"=>"Heart Diseases"}, {"id"=>"D002318", "term"=>"Cardiovascular Diseases"}], "browseLeaves"=>[{"id"=>"M7115", "name"=>"Diabetes Mellitus", "relevance"=>"LOW"}, {"id"=>"M7119", "name"=>"Diabetes Mellitus, Type 2", "relevance"=>"LOW"}, {"id"=>"M9421", "name"=>"Heart Failure", "asFound"=>"Heart Failure", "relevance"=>"HIGH"}, {"id"=>"M9419", "name"=>"Heart Diseases", "relevance"=>"LOW"}], "browseBranches"=>[{"name"=>"Nutritional and Metabolic Diseases", "abbrev"=>"BC18"}, {"name"=>"Gland and Hormone Related Diseases", "abbrev"=>"BC19"}, {"name"=>"All Conditions", "abbrev"=>"All"}, {"name"=>"Heart and Blood Diseases", "abbrev"=>"BC14"}]}, "interventionBrowseModule"=>{"meshes"=>[{"id"=>"C570240", "term"=>"Empagliflozin"}, {"id"=>"C027696", "term"=>"Acipimox"}], "ancestors"=>[{"id"=>"D000077203", "term"=>"Sodium-Glucose Transporter 2 Inhibitors"}, {"id"=>"D045504", "term"=>"Molecular Mechanisms of Pharmacological Action"}, {"id"=>"D007004", "term"=>"Hypoglycemic Agents"}, {"id"=>"D045505", "term"=>"Physiological Effects of Drugs"}, {"id"=>"D000960", "term"=>"Hypolipidemic Agents"}, {"id"=>"D000963", "term"=>"Antimetabolites"}, {"id"=>"D057847", "term"=>"Lipid Regulating Agents"}], "browseLeaves"=>[{"id"=>"M258082", "name"=>"Empagliflozin", "asFound"=>"Evening", "relevance"=>"HIGH"}, {"id"=>"M1691", "name"=>"Sodium-Glucose Transporter 2 Inhibitors", "relevance"=>"LOW"}, {"id"=>"M229334", "name"=>"Acipimox", "asFound"=>"Elliptical", "relevance"=>"HIGH"}, {"id"=>"M10054", "name"=>"Hypoglycemic Agents", "relevance"=>"LOW"}, {"id"=>"M4278", "name"=>"Hypolipidemic Agents", "relevance"=>"LOW"}, {"id"=>"M4281", "name"=>"Antimetabolites", "relevance"=>"LOW"}, {"id"=>"M28883", "name"=>"Lipid Regulating Agents", "relevance"=>"LOW"}], "browseBranches"=>[{"name"=>"Hypoglycemic Agents", "abbrev"=>"Hypo"}, {"name"=>"All Drugs and Chemicals", "abbrev"=>"All"}, {"name"=>"Lipid Regulating Agents", "abbrev"=>"Lipd"}]}}, "protocolSection"=>{"designModule"=>{"phases"=>["EARLY_PHASE1"], "studyType"=>"INTERVENTIONAL", "designInfo"=>{"allocation"=>"RANDOMIZED", "maskingInfo"=>{"masking"=>"DOUBLE", "whoMasked"=>["PARTICIPANT", "INVESTIGATOR"], "maskingDescription"=>"Participants, and investigators will be blinded to the randomization"}, "primaryPurpose"=>"BASIC_SCIENCE", "interventionModel"=>"PARALLEL", "interventionModelDescription"=>"A randomized (2:1) placebo controlled double blind study"}, "enrollmentInfo"=>{"type"=>"ESTIMATED", "count"=>71}}, "statusModule"=>{"overallStatus"=>"RECRUITING", "startDateStruct"=>{"date"=>"2024-01-25", "type"=>"ACTUAL"}, "expandedAccessInfo"=>{"hasExpandedAccess"=>false}, "statusVerifiedDate"=>"2024-02", "completionDateStruct"=>{"date"=>"2027-03-01", "type"=>"ESTIMATED"}, "lastUpdateSubmitDate"=>"2024-02-13", "studyFirstSubmitDate"=>"2023-12-18", "studyFirstSubmitQcDate"=>"2024-01-18", "lastUpdatePostDateStruct"=>{"date"=>"2024-02-15", "type"=>"ACTUAL"}, "studyFirstPostDateStruct"=>{"date"=>"2024-01-29", "type"=>"ACTUAL"}, "primaryCompletionDateStruct"=>{"date"=>"2026-11-01", "type"=>"ESTIMATED"}}, "outcomesModule"=>{"primaryOutcomes"=>[{"measure"=>"Change in Phosphocreatine", "timeFrame"=>"Baseline to 3 months", "description"=>"A measure of phosphocreatine change from baseline to study end"}, {"measure"=>"Change in Adenosine Triphosphate (ATP)", "timeFrame"=>"Baseline to 3 months", "description"=>"A measure of ATP change from baseline to study end"}, {"measure"=>"Change in Inorganic Phosphate", "timeFrame"=>"Baseline to 3 months", "description"=>"A measure of inorganic phosphate change from baseline to study end"}, {"measure"=>"Change in Phosphodiester", "timeFrame"=>"Baseline to 3 months", "description"=>"A measure of phosphodiester change from baseline to study end"}, {"measure"=>"ATPmax production", "timeFrame"=>"Baseline to 3 months", "description"=>"Exercise induced ATPmax production change"}], "secondaryOutcomes"=>[{"measure"=>"Plasma Beta-hydroxybutyrate (β-OH-B)", "timeFrame"=>"baseline to 3 months", "description"=>"Change in β-OH-B with medication"}, {"measure"=>"Acetoacetate concentrations", "timeFrame"=>"baseline to 3 months", "description"=>"Change in acetoacetate concentrations"}, {"measure"=>"6-min walking test", "timeFrame"=>"baseline to 3 months", "description"=>"Change in the distance that can be covered in a 6 minute walk test"}, {"measure"=>"Patient-Reported Outcomes Measure Information System", "timeFrame"=>"baseline to 3 months", "description"=>"By checking KCCQ (Kansas City Cardiomyopathy) scoring: Responses are categorized under 3 sub scales (symptom burden, physical limitation and quality of life) with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The total KCCQ score represents the mean of the three sub scale scores."}, {"measure"=>"plasma ketone concentration on myocardial function", "timeFrame"=>"Baseline to 3months + 8 days", "description"=>"To examine the contribution of the SGLT2i-induced increase in plasma ketone concentration on myocardial function by inhibiting the rise in plasma ketone concentration with acipimox while continuing empagliflozin."}, {"measure"=>"plasma ketone concentration on myocardial blood flow", "timeFrame"=>"Baseline to 3months + 8 days", "description"=>"To examine the contribution of the SGLT2i-induced increase in plasma ketone concentration on myocardial blood flow by inhibiting the rise in plasma ketone concentration with acipimox while continuing empagliflozin."}]}, "oversightModule"=>{"oversightHasDmc"=>false, "isFdaRegulatedDrug"=>true, "isFdaRegulatedDevice"=>false}, "conditionsModule"=>{"keywords"=>["ketones", "cardiovascular benefit"], "conditions"=>["Type2diabetes", "Heart Failure With Reduced Ejection Fraction"]}, "descriptionModule"=>{"briefSummary"=>"The study team will examine the effects of elevated plasma ketone levels following initiation of SGLT2 inhibitor therapy in high-risk type 2 diabetes mellitus (T2DM) individuals with heart failure (HF) with reduced ejection fraction (HFrEF) providing an energy-rich fuel that is taken up with great avidity by the myocardium, to measure change in Left Ventricle diastolic and systolic function", "detailedDescription"=>"The study team will examine the effects of elevated plasma ketones caused by 12-week treatment with an SGLT2i (empagliflozin) treatment in participants with T2DM and HF. The study team will focus on three possible mechanisms of action for these effects and test the following:\n\n(i) Skeletal muscle bioenergetics. Using 31P-MRS, the team will quantify phosphocreatine \\[PCr\\], ATP, inorganic phosphate, phosphodiester, and intracellular pH. With 1H-MRS, and will measure intramyocellular lipid content at rest and ATPmax production after exercise. The team will examine the relationships between phosphorous metabolite concentrations, intramyocellular lipid content, and ATP generation before and after 12 weeks of SGLT2 inhibition.\n\n(ii) LV systolic and diastolic function using cardiac MRI in type 2 diabetic patients with Class II-III NYHA heart failure and reduced EF.\n\n(iii) To examine the contribution of the SGLT2i-induced increase in plasma ketone concentration on myocardial function and myocardial blood flow by inhibiting the rise in plasma ketone concentration with acipimox while continuing empagliflozin.\n\n(iv) Improvements in Patient-Reported Outcomes (PRO). Kansas City Cardiomyopathy Questionnaire ( KCCQ) scoring will be used to evaluate self-reported physical function and well-being. This tool is a well-developed and validated method to obtain patient self-reported parameters of health in adults."}, "eligibilityModule"=>{"sex"=>"ALL", "stdAges"=>["ADULT", "OLDER_ADULT"], "maximumAge"=>"70 years", "minimumAge"=>"18 years", "healthyVolunteers"=>false, "eligibilityCriteria"=>"Inclusion Criteria:\n\n* Type 2 Diabetes Mellitus\n* Class II-III New York Heart Association (NYHA) heart failure and reduced ejection fraction (EF) \\<50%\n* Age 18-80 years\n* BMI 23-38 kg/m2\n* Glycated hemoglobin (HbA1c) 5.5-10%\n* Blood Pressure (BP) ≤ 145/85 mmHg\n* Estimated glomerular filtration rate (eGFR) ≥30 ml/min•1.73 m2\n* Stable dose of guideline-directed medications for heart failure\n* Stable body weight (±4 pounds) over the last 3 months\n\nExclusion Criteria:\n\n* Subjects treated with an SGLT2 inhibitor, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or pioglitazone\n* Resting heart rate \\>120 bpm\n* Systolic BP\\>180mmHg and/or diastolic BP \\>100mmHg\n* Resting percentage of blood oxygen saturation (SpO2) \\< 85%\n* Physical disability preventing safe performance of the exercise protocol."}, "identificationModule"=>{"nctId"=>"NCT06229678", "briefTitle"=>"Ketones, SGLT2, HFrEF", "organization"=>{"class"=>"OTHER", "fullName"=>"The University of Texas Health Science Center at San Antonio"}, "officialTitle"=>"Ketones, Muscle Metabolism, and SGLT2 Inhibitors", "orgStudyIdInfo"=>{"id"=>"STUDY00000012"}, "secondaryIdInfos"=>[{"id"=>"R01DK107680", "link"=>"https://reporter.nih.gov/quickSearch/R01DK107680", "type"=>"NIH"}]}, "armsInterventionsModule"=>{"armGroups"=>[{"type"=>"EXPERIMENTAL", "label"=>"Empagliflozin Group", "description"=>"Subjects will be randomized 2:1 to receive empagliflozin, 25mg/day for 3 months", "interventionNames"=>["Drug: Empagliflozin 25 MG Oral Tablet", "Drug: Acipimox 250 Mg Oral Capsule"]}, {"type"=>"PLACEBO_COMPARATOR", "label"=>"Placebo group", "description"=>"Subjects will be randomized to receive the empagliflozin placebo for 3 months", "interventionNames"=>["Drug: Placebo", "Drug: Acipimox 250 Mg Oral Capsule"]}], "interventions"=>[{"name"=>"Empagliflozin 25 MG Oral Tablet", "type"=>"DRUG", "otherNames"=>["jardiance"], "description"=>"Empagliflozin 25MG will be administered orally once per day for 3 months", "armGroupLabels"=>["Empagliflozin Group"]}, {"name"=>"Placebo", "type"=>"DRUG", "description"=>"The placebo will be administered orally once per day for 3 months", "armGroupLabels"=>["Placebo group"]}, {"name"=>"Acipimox 250 Mg Oral Capsule", "type"=>"DRUG", "description"=>"subjects will be started on acipimox 250mg every 6 hours for 8 days while on continued empagliflozin/placebo therapy. This will be added at the end of 3 months after they finished baseline studies", "armGroupLabels"=>["Empagliflozin Group", "Placebo group"]}]}, "contactsLocationsModule"=>{"locations"=>[{"zip"=>"78207", "city"=>"San Antonio", "state"=>"Texas", "status"=>"RECRUITING", "country"=>"United States", "contacts"=>[{"name"=>"Sivaram Neppala, MD", "role"=>"CONTACT", "email"=>"neppalas@uthscsa.edu", "phone"=>"210-358-7200"}, {"name"=>"Jemema Rajan, MD", "role"=>"CONTACT", "email"=>"rajanj@uthscsa.edu", "phone"=>"210-358-7200"}, {"name"=>"Ralph DeFronzo, MD", "role"=>"PRINCIPAL_INVESTIGATOR"}, {"name"=>"Sivaram Neppala, MD", "role"=>"SUB_INVESTIGATOR"}, {"name"=>"Jemema Rajan, MD", "role"=>"SUB_INVESTIGATOR"}], "facility"=>"Texas Diabetes Institute - University Health System", "geoPoint"=>{"lat"=>29.42412, "lon"=>-98.49363}}], "centralContacts"=>[{"name"=>"Ralph DeFronzo, MD", "role"=>"CONTACT", "email"=>"defronzo@uthscsa.edu", "phone"=>"210-567-6691"}, {"name"=>"Sivaram Neppala, MD", "role"=>"CONTACT", "email"=>"neppalas@uthscsa.edu", "phone"=>"210-358-7200"}], "overallOfficials"=>[{"name"=>"Ralph DeFronzo, MD", "role"=>"PRINCIPAL_INVESTIGATOR", "affiliation"=>"University of Texas Health Science Center San Antonio"}]}, "ipdSharingStatementModule"=>{"infoTypes"=>["STUDY_PROTOCOL", "SAP"], "ipdSharing"=>"YES", "description"=>"The PI will actively participate in journal clubs and symposia and present abstracts at national meetings, as well as submit manuscripts to top peer-reviewed journals."}, "sponsorCollaboratorsModule"=>{"leadSponsor"=>{"name"=>"The University of Texas Health Science Center at San Antonio", "class"=>"OTHER"}, "collaborators"=>[{"name"=>"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)", "class"=>"NIH"}], "responsibleParty"=>{"type"=>"SPONSOR"}}}}
