Ignite Creation Date:
2025-12-25 @ 4:35 AM
Ignite Modification Date:
2026-03-09 @ 8:37 AM
Study NCT ID:
NCT04080518
Status:
COMPLETED
Last Update Posted:
2023-04-13
First Post:
2019-08-26
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'id': 'D006333', 'term': 'Heart Failure'}], 'ancestors': [{'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': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C529054', 'term': 'dapagliflozin'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR'], 'maskingDescription': 'The assignment of consented patients will occur in a blinded fashion using a randomization scheme generated by a statistician who is not part of the study team and has no contact with the study subject. Once eligibility criteria are met, study participants will be randomly assigned to receive either Dapagliflozin 10mg or matching, identically appearing placebo. Stratified random sampling (by gender) will be performed in order to minimize selection bias. Access to the randomisation code will be controlled and documented. Relevant parties will be blinded to the treatment group assignment.'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'This study will be a 4-week double blind, placebo-controlled, randomized study with 2 treatment arms.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 40}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2019-11-11', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-04', 'completionDateStruct': {'date': '2021-11-10', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-04-11', 'studyFirstSubmitDate': '2019-08-26', 'studyFirstSubmitQcDate': '2019-09-04', 'lastUpdatePostDateStruct': {'date': '2023-04-13', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-09-06', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-11-10', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'To demonstrate that SGLT-2 inhibition induces urea-dominated renal water conservation within the renal concentration mechanism. ( Change from baseline in urinary osmolyte concentration', 'timeFrame': 'Baseline, Day 3, and Day 28.', 'description': 'Change from baseline in urinary osmolyte concentration\n\n1. Change from baseline in Na+\n2. Change from baseline in urea concentration'}], 'secondaryOutcomes': [{'measure': 'To demonstrate that SGLT-2 inhibition increases plasma co-peptin levels in an effort to prevent dehydration', 'timeFrame': 'Baseline, Day 3 and Day 28', 'description': 'The investigators will study the changes in plasma co-peptin levels shortly after SGLT-2 inhibitor treatment initiation.'}, {'measure': 'Analysis of skin and muscle Na+ content', 'timeFrame': 'Baseline, Day 3, and Day 28.', 'description': 'The investigators will compare the changes in skin and muscle Na+ content shortly after SGLT-2 inhibitor treatment initiation. Tissue Na+ content will be measured non-invasively with 23NaMRI, using a Siemens 3T MRI scanner system.'}, {'measure': 'Analysis of glycogen and fat content in skeletal muscle and liver', 'timeFrame': 'Baseline, Day 3 and Day 28', 'description': 'The investigators will compare changes from baseline in muscle and liver lipid content (measured with 1HMRS) and assess glycogen content by metabolomic analysis in patients treated with dapagliflozin versus those receiving placebo'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Diabetes Mellitus', 'Heart Failure']}, 'referencesModule': {'references': [{'pmid': '38599715', 'type': 'DERIVED', 'citation': 'Marton A, Saffari SE, Rauh M, Sun RN, Nagel AM, Linz P, Lim TT, Takase-Minegishi K, Pajarillaga A, Saw S, Morisawa N, Yam WK, Minegishi S, Totman JJ, Teo S, Teo LLY, Ng CT, Kitada K, Wild J, Kovalik JP, Luft FC, Greasley PJ, Chin CWL, Sim DKL, Titze J. Water Conservation Overrides Osmotic Diuresis During SGLT2 Inhibition in Patients With Heart Failure. J Am Coll Cardiol. 2024 Apr 16;83(15):1386-1398. doi: 10.1016/j.jacc.2024.02.020.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to investigate the effects of Dapagliflozin (FORXIGA) 10mg (n=20) and placebo (n=20) on the renal concentration mechanism, mobilization of Na+ from tissue stores, and mobilization of muscle glycogen and fat, in patients heart failure NYHA classes I and II,with or w/o T2DM in a 4-week double-blind, placebo-controlled, randomized study with 2 treatment arms.', 'detailedDescription': 'Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are a new class of oral medications used for T2DM, which lower blood glucose levels by increasing renal sodium (Na+) and glucose excretion. However, their applications seem to go beyond glycemic control. Recent studies have shown that treatment with SGLT-2 inhibitors significantly improves cardiovascular outcome, with unprecedented reductions in cardiovascular mortality and heart failure hospitalizations. The underlying mechanism of this surprising effect is unclear.\n\nOur hypothesis is that increased Na+ and glucose excretion induced by SGLT-2 inhibitors predisposes to water loss, to which the body responds by increasing urea production in an effort to prevent dehydration. Urea is accumulated in the renal medulla, where it provides the alternative osmotic driving force for water reabsorption. However, hepatic urea production is an energy-intense process, for which amino acids from skeletal muscle are the ideal fuel because they provide both the nitrogen and the energy needed for urea generation. Alanine is transported from muscle to the liver, where it serves as a substrate for new pyruvate generation, which can then be used for the urea cycle, glucose production or ketone body generation. In the same time, as increasing amounts of alanine are shuttled to the liver, muscle will deplete its glucose reservoirs and reprioritize fuel utilization in favour of fatty acids.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '21 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Diagnosis of heart failure NYHA stage I or II - as shown by their medical records\n2. Stable anti-hypertensive treatment (\\>4 weeks)\n3. Male and female patients older than 21 years\n4. Willingness to participate and ability to provide informed consent\n5. Willingness to use effective birth control if of childbearing potential. Any kind of contraception method will be allowed for the period of the study\n\nExclusion Criteria:\n\n1. Patients with congestive heart failure NYHA stages I (LVEF \\>40%) without type 2 diabetes mellitus.\n2. Patients with congestive heart failure NYHA stages III and IV\n3. Prior serious hypersensitivity reaction to Dapagliflozin (Forxiga®)\n4. Treatment with any SGLT-2 inhibitor or combined SGLT-1 and 2 inhibitors within 1 week prior to Visit 1 or during screening period until Visit 1\n5. Pregnant and breast-feeding women\n6. Diagnosis of type 1 diabetes mellitus\n7. Patients with type 2 diabetes mellitus with HbA1C \\> 10.5% from most recent medical records or antidiabetic therapies other than metformin, sulfonylureas or gliptins at screening.\n8. Patients with type 2 diabetes mellitus whose antidiabetic treatment (metformin and/or sulfonylureas and/or gliptins) has been changed or unstable within 6 weeks prior to Visit 1\n9. . Unstable or rapidly progressing renal disease\n10. Chronic cystitis and recurrent urinary tract infections\n11. Impaired renal function with eGFR\\<45 ml/min/1.73m2 or proteinuria \\> 0.5 g/24h\n12. Severe hepatic impairment (Child-Pugh class C)\n13. Any major cardiovascular event/vascular disease within 3 months prior to enrolment, as assessed by the investigator\n14. Severe edema (as judged by the investigator)\n15. Active cancer, history of bladder cancer\n16. HIV infection\n17. Patients who have received an organ or bone marrow transplant\n18. Patients who have had major surgery in the past 3 months\n19. Patients who have severe comorbid conditions likely to compromise survival or study participation\n20. Patients who exhibit noticeable anxiety and/or claustrophobia or who exhibit severe vertigo when they are moved into the MRI scanner\n21. Patients with exclusion criteria for the MRI, such as:\n\n 1. implanted devices (surgical clips, heart pacemakers or defibrillators, cochlear implants)\n 2. iron-based tattoos\n 3. any other pieces of metal or devices that are not MR-Safe anywhere in the body\n22. Unwillingness or other inability to cooperate'}, 'identificationModule': {'nctId': 'NCT04080518', 'acronym': 'DAPA-Shuttle1', 'briefTitle': 'Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment', 'organization': {'class': 'OTHER', 'fullName': 'National Heart Centre Singapore'}, 'officialTitle': 'Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment', 'orgStudyIdInfo': {'id': '2018/2414'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Experimental', 'description': 'Dapagliflozin, 10mg, oral dose, once every day', 'interventionNames': ['Drug: Dapagliflozin 10 MG [Forxiga]']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Control', 'description': 'Matching placebo for dapagliflozin, oral dose, once every day', 'interventionNames': ['Drug: Dapagliflozin 10 MG [Forxiga]']}], 'interventions': [{'name': 'Dapagliflozin 10 MG [Forxiga]', 'type': 'DRUG', 'otherNames': ['Placebo'], 'description': '24 Hour Urine Collection, Sodium (23Na) MRI and Magnetic Resonance (MR) spectroscopy scan, Blood collection for metabolomic and osmolyte analysis', 'armGroupLabels': ['Control', 'Experimental']}]}, 'contactsLocationsModule': {'locations': [{'zip': '169609', 'city': 'Singapore', 'country': 'Singapore', 'facility': 'National Heart Centre Singapore', 'geoPoint': {'lat': 1.28967, 'lon': 103.85007}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Heart Centre Singapore', 'class': 'OTHER'}, 'collaborators': [{'name': 'Duke-NUS Graduate Medical School', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}