A Phase 4 interventional study of Dapagliflozin 10 MG [Forxiga] in Diabetes Mellitus and Heart Failure, sponsored by National Heart Centre Singapore. Completed at 1 site in Singapore. Open to participants aged 21 Years and older. Per ClinicalTrials.gov, last updated 2023-04-13.
Sponsored by National Heart Centre Singapore · Phase 4, Interventional, and Basic science
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.
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.
Our 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.
5,701 studies on the registry are indexed under Heart Failure; 1,219 are open to participants now.
This study's enrollment of 40 is below the median of 72 across 3,733 interventional studies indexed under Heart Failure.
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Exclusion Criteria:
Patients with exclusion criteria for the MRI, such as:
Dapagliflozin, 10mg, oral dose, once every day
Drug: Dapagliflozin 10 MG [Forxiga]
Matching placebo for dapagliflozin, oral dose, once every day
Drug: Dapagliflozin 10 MG [Forxiga]
24 Hour Urine Collection, Sodium (23Na) MRI and Magnetic Resonance (MR) spectroscopy scan, Blood collection for metabolomic and osmolyte analysis
Also known as: Placebo
To demonstrate that SGLT-2 inhibition induces urea-dominated renal water conservation within the renal concentration mechanism. ( Change from baseline in urinary osmolyte concentration
Change from baseline in urinary osmolyte concentration 1. Change from baseline in Na+ 2. Change from baseline in urea concentration
Time frame: Baseline, Day 3, and Day 28.
To demonstrate that SGLT-2 inhibition increases plasma co-peptin levels in an effort to prevent dehydration
The investigators will study the changes in plasma co-peptin levels shortly after SGLT-2 inhibitor treatment initiation.
Time frame: Baseline, Day 3 and Day 28
Analysis of skin and muscle Na+ content
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.
Time frame: Baseline, Day 3, and Day 28.
Analysis of glycogen and fat content in skeletal muscle and liver
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
Time frame: Baseline, Day 3 and Day 28
Plan to share: No
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This study is completed, as verified in Apr 2023. You cannot join it, but the record below documents what was studied.
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National Heart Centre Singapore