Ignite Creation Date:
2025-12-25 @ 1:19 AM
Ignite Modification Date:
2025-12-25 @ 11:27 PM
Study NCT ID:
NCT07053293
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, Hepatic Glucose Production, and SNS
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': ['EARLY_PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'None (Open Label)'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'A clinical trial comprised of 2 studies'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 22}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-01-07', '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': 'Endogenous Glucose Production (EGP)', 'timeFrame': '0 and 300 minutes', 'description': 'Measurement of Endogenous Glucose Production (EGP) using stable isotope (6,6, D2- glucose infusion).'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Endogenous glucose production', 'Ketogenesis', 'Gluconeogenesis', 'Lipolysis', 'Norepinephrine turnover'], 'conditions': ['Type 2 Diabetes']}, 'descriptionModule': {'briefSummary': 'In this study, PI will test the hypothesis that distinct mechanisms account for the SGLT2i-induced stimulation of ketogenesis and lipolysis versus endogenous (hepatic) glucose production in patients with type 2 diabetes (T2D) that the increases in ketone production and lipolysis can be prevented by concomitant administration of the thiazolidinedione pioglitazone. Principal Investigator (PI) will conduct five distinct experiments to test this hypothesis in patients with T2D.\n\nTo examine the role of the SNS on the empagliflozin-induced stimulation of EGP, lipolysis, and ketone production in T2D by comparing the effect of empagliflozin versus empagliflozin plus propranolol.', 'detailedDescription': 'Protocol: 22 T2D Subjects will be randomized to receive empagliflozin (n=20). Each subject will participate in two studies performed in random order. In Study 1, EGP will be measured with a prime-continuous 6,6, D2-glucose infusion and lipolysis will be measured with prime-continuous infusion of U-2H-glycerol. The rate of ketogenesis will be determined by infusion of 13C palmitate and quantitating the enrichment of 13C in 3-hydroxybutyrate (BHB). Total body NE turnover will be measured with 3H-norepinephrine (3H-NE) infusion before and after empagliflozin administration.\n\nVisit 2 (Study 1): At approximately 6:00PM on the night prior to study subjects will ingest D2O (3 grams/kg ffm) to quantitate gluconeogenesis and de novo lipogenesis. At 6:00AM at Visit 1 prime-continuous infusions of 6,6, D2-glucose and U-2H-glycerol or U-14C-glycerol are started and continued to study end to measure rates of hepatic glucose production (HGP) and lipolysis. At 8:00AM a prime-continuous infusion of 3H-norepinephrine is started and continued to 9:00 AM at which time it will be stopped. Empagliflozin 25mg is administered at this time, 9:00 AM. At 1:00 PM (240 minutes after administration of Empagliflozin) a second prime-continuous 3H-Norepinephrine infusion is started for 60 minutes. Detailed explanation on page 52-53.\n\nVisit 3 (Study 2, Optional): At approximately 6:00PM on the night prior to study subjects will ingest D2O (3 grams/kg ffm) to quantitate gluconeogenesis and de novo lipogenesis. This visit will be identical to Visit 2 for Aim 2 (Sub-study I) with one exception. At 8:30AM, 30 minutes prior to the ingestion of the Empagliflozin 25mg, a prime (200 ug/kg over 20 minutes)-continuous (80 ug/min) infusion of propranolol is started and continued to study end. Principal Investigator (PI) previously have shown that the steady state propranolol concentration achieved by this infusion rate is sufficient to significantly inhibit insulin-mediated glucose disposal.'}, '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': 'NCT07053293', 'briefTitle': 'SGLT2i, Hepatic Glucose Production, and SNS', 'organization': {'class': 'OTHER', 'fullName': 'The University of Texas Health Science Center at San Antonio'}, 'officialTitle': 'Protocol II: SGLT2i, Hepatic Glucose Production, and Sympathetic Nervous System (SNS)', 'orgStudyIdInfo': {'id': '20230457HU - 504075'}, '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'}}}}