Ignite Creation Date:
2025-12-26 @ 2:42 PM
Ignite Modification Date:
2025-12-26 @ 2:42 PM
Study NCT ID:
NCT07053306
Status:
RECRUITING
Last Update Posted:
2025-07-11
First Post:
2025-06-26
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
SGLT2i, Ketoacidosis, Volume Contraction, and Insulinopenia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003924', 'term': 'Diabetes Mellitus, Type 2'}], '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'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C570240', 'term': 'empagliflozin'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'None (Open Label)'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'A randomized controlled 1 arm clinical trial comprised of 4 studies'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 29}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-04-29', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2027-06-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-07-08', 'studyFirstSubmitDate': '2025-06-26', 'studyFirstSubmitQcDate': '2025-06-26', 'lastUpdatePostDateStruct': {'date': '2025-07-11', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-07-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-06-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Ketone Body Turnover (ketogenesis)', 'timeFrame': '0 and 300 minutes', 'description': 'Measurement of ketone body turnover rate during the baseline state and 240-300-minute time period, before and after Empagliflozin administration.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Pancreatic clamp', 'Endogenous glucose production', 'Ketogenesis', 'Gluconeogenesis', 'Lipolysis'], 'conditions': ['Type 2 Diabetes']}, 'descriptionModule': {'briefSummary': 'To examine the 2-HIT hypothesis that the SGLT2i-induced stimulation of EGP, lipolysis, and ketone production requires the combination of volume depletion plus insulinopenia in T2D individuals.', 'detailedDescription': 'After screening visit, subjects will participate in four additional visits and or at least one of the four visits that will be performed in random order starting at 6:00 AM to the Clinical Research Center at University Hospital-Texas Diabetes Institute.\n\nVisit 2 (Study 1): At 6:00AM at (Study 1), a prime-continuous infusions of 6,6, D2-Glucose or U-3H-glucose and U-2H-glycerol or U-14C-Glycerol are started and continued to study end (2:00 PM) to measure rates of hepatic glucose production (HGP) and fat break down (lipolysis).3H-Glucose infusion to be given: (Prime=25µCi x (FPG/100), Continuous=0.25µCi/min x 480 min=120µCi). At time zero (9:00 AM) subjects will ingest Empagliflozin (25 mg). Plasma substrate, hormone concentrations, U-3H-glucose and U-14C-glycerol specific activities will be measured every 5-30 minutes for 300 minutes (2:00 PM) and 295 minutes. If Principal Investigator (PI) use U-2H-glycerol instead of U-14C Glycerol, PI will measure plasma U-2H-glycerol enrichment instead of U-14C-glycerol specific activities. Detailed explanation on page 54, if PI will use U-6,6, D2-Glucose instead of U-3H Glucose, PI will measure plasma 2H-Glucose enrichment instead of 3H Glucose specific activities. Detailed explanation on page 54.\n\nVisit 3 (Study 2, Optional): At 6:00AM prime-continuous infusions of 6,6, D2-Glucose or U-3H-Glucose and U-2H-glycerol or U-14C-Glycerol are started and continued to study end (2:00 PM) to measure rates of hepatic glucose production (HGP) and lipolysis. 3H-Glucose infusion to be given: (Prime=25µCi x (FPG/100), Continuous=0.25µCi/min x 480 min=120µCi). At 7 AM an infusion of normal saline will be started at the rate of 150 ml/hour and continued to the end of study at 2 PM (total volume = 1050 ml; total Na and Cl = 154 meq) to provide volume replacement for blood loss. At time zero (9:00 AM) subjects will ingest Empagliflozin (25 mg). Plasma substrate, hormone concentrations, 3H-glucose and 14C-glycerol specific activities will be measured every 5-30 minutes for 300 minutes (2:00 PM) and 295 minute. If PI use U-2H-glycerol instead of U-14C Glycerol, PI will measure plasma U-2H-glycerol enrichment instead of U-14C-glycerol specific activities. Detailed explanation on page 55. If PI use U-6,6, D2-Glucose instead of U-3H Glucose, PI will measure plasma 2H-Glucose enrichment instead of 3H Glucose specific activities. Detailed explanation on page 55.\n\nVisit 4 (Study 3, Optional): At 6:00AM prime-continuous infusions 6,6, D2-Glucose or U-3H-Glucose and U-2H-glycerol or U-14C-Glycerol are started and continued to study end (2:00 PM) to measure rates of Hepatic Glucose Production (HGP) and fat break down (lipolysis). 3H-Glucose infusion to be given: (Prime=25µCi x (FPG/100), Continuous=0.25µCi/min x 480 min=120µCi). At time zero (9:00 AM) subjects will ingest Empagliflozin (25 mg) and octreotide or somatostatin with insulin and glucagon will be given to reduce volume without insulinopenia. Plasma substrate and hormone concentrations and 3H-glucose/14C-glycerol specific activities will be measured every 5-30 minutes for 300 minutes (2:00 PM) and 295 minute. If PI use U-2H-glycerol instead of U-14C Glycerol, PI will measure plasma U-2H-glycerol enrichment instead of U-14C-glycerol specific activities. Detailed explanation on page 55-56. If PI uses U-6,6, D2-Glucose instead of U-3H Glucose, PI will measure plasma 2H-Glucose enrichment instead of 3H Glucose specific activities. Detailed explanation on page 56.\n\nVisit 5 (Study 4, Optional): At 6:00AM prime-continuous infusions of 6,6, D2-Glucose or 3H-Glucose and U-2H-glycerol or U-14C-Glycerol are started and continued to study end (2:00 PM) to measure rates of hepatic (liver) glucose production (HGP) and fat break down (lipolysis). 3H-Glucose infusion to be given: (Prime=25µCi x (FPG/100), Continuous=0.25µCi/min x 480 min=120µCi). At 7 AM an infusion of normal saline will be started at the rate of 150 ml/hour and continued to the end of study at 2 PM (total volume = 1050 ml; total Na and Cl = 154 meq) to provide volume replacement for blood loss. At time zero (9:00 AM) subjects will ingest empagliflozin (25 mg) and octreotide or somatostatin with insulin and glucagon will be given. Plasma substrate and hormone concentrations and 3H-glucose/14C-glycerol specific activities will be measured every 5-30 minutes for 300 minutes (2:00 PM) and 295 minute. If PI uses U-2H-glycerol instead of U-14C Glycerol, PI will measure plasma U-2H-glycerol enrichment instead of U-14C-glycerol specific activities. Detailed explanation on page 56. If PI use U-6,6, D2-Glucose instead of U-3H Glucose, PI will measure plasma 2H-Glucose enrichment instead of 3H Glucose specific activities. Detailed explanation on page 56.\n\nIn Substudy II, PI will use stable isotopes (6,6-D2-glucose and U-2H-glycerol) or radioisotopes (U-3H-glucose and U-14C-glycerol) to measure endogenous glucose production (EGP) and fat breakdown (lipolysis), depending on isotope availability and cost. Both sets of isotopes will provide the necessary data to address research objectives.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '30 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Patients with T2D\n\nInclusion Criteria:\n\n* Ages 30-75 years\n* Body Mass Index (BMI) 21-45 kg/m2\n* Hemoglobin A1C (HbA1c) = 7.0-11%\n* Estimated glomerular filtration rate (eGFR) \\> 60 ml/min/1.73m2\n* Blood Pressure (BP) \\< 160/90 mmHg\n* Participants must be in general good health based on medical history, physical exam, screening blood chemistries, complete blood chemistry (CBC), thyroid stimulating hormone/thyroxine (TSH/T4), electrocardiogram (EKG), and urinalysis\n* Stable body weight (±1.5 kg) over the last 3 months and must not participate in an excessively heavy exercise program\n* Patients treated with diet, sulfonylurea (SU), metformin (MET), or SU/MET\n* Statin therapy is permissible if the dose has been stable for at least 3 months\n\nExclusion Criteria:\n\n* Patients treated with Glucagon-like peptide 1 receptor agonists (GLP-1 RA), Dipeptidyl Peptidase IV inhibitors (DPP-4i), Thiazolidinediones (TZD), or insulin are excluded\n* Patients taking medications (other than SU/MET) known to affect glucose metabolism are excluded\n* Subjects with evidence of proliferative retinopathy or eGFR \\< 60 are excluded\n* Women of childbearing potential are excluded unless they are taking/using appropriate contractive medications/devices'}, 'identificationModule': {'nctId': 'NCT07053306', 'briefTitle': 'SGLT2i, Ketoacidosis, Volume Contraction, and Insulinopenia', 'organization': {'class': 'OTHER', 'fullName': 'The University of Texas Health Science Center at San Antonio'}, 'officialTitle': 'Protocol III: SGLT2i, Ketoacidosis, Volume Contraction, and Insulinopenia', 'orgStudyIdInfo': {'id': '20230457HU - 504076'}, 'secondaryIdInfos': [{'id': 'R01DK024092', 'link': 'https://reporter.nih.gov/quickSearch/R01DK024092', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Empagliflozin', 'description': 'Empagliflozin 25 mg/day', 'interventionNames': ['Drug: Empagliflozin 25 MG']}], 'interventions': [{'name': 'Empagliflozin 25 MG', 'type': 'DRUG', 'otherNames': ['Jardiance'], 'description': 'A medication used in the management and treatment of type 2 diabetes mellitus. It is in the sodium-glucose co-transporter (SGLT-2) class of medications.', 'armGroupLabels': ['Empagliflozin']}]}, 'contactsLocationsModule': {'locations': [{'zip': '78229-3900', 'city': 'San Antonio', 'state': 'Texas', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Ralph DeFronzo, MD', 'role': 'CONTACT', 'email': 'defronzo@uthscsa.edu', 'phone': '210-358-7200'}, {'name': 'Aurora Merovci, MD', 'role': 'CONTACT', 'email': 'merovci@uthscsa.edu', 'phone': '210-567-6691'}, {'name': 'Ralph DeFronzo, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Texas Diabetes Institute/UH', 'geoPoint': {'lat': 29.42412, 'lon': -98.49363}}], 'centralContacts': [{'name': 'Ralph DeFronzo, MD', 'role': 'CONTACT', 'email': 'defronzo@uthscsa.edu', 'phone': '210-567-6691'}, {'name': 'Aurora Merovci, MD', 'role': 'CONTACT', 'email': 'merovci@uthscsa.edu', 'phone': '210-567-6691'}], 'overallOfficials': [{'name': 'Ralph DeFronzo, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Texas Health Science Center San Antonio'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'SAP', 'ICF'], 'timeFrame': 'At study end after analysis of data.', 'ipdSharing': 'YES', 'description': 'Deidentified data will be shared with NIH and as a publication in a peer reviewed journal once data are published.'}, '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'}}}}