Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment

NCT04080518 | Completed Phase 4

• 1 other identifier: 2018/2414
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetes Mellitus; Heart Failure

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline, Day 3, and Day 28.

Secondary Outcomes (3)

• To demonstrate that SGLT-2 inhibition increases plasma co-peptin levels in an effort to prevent dehydration

  Baseline, Day 3 and Day 28

• Analysis of skin and muscle Na+ content

  Baseline, Day 3, and Day 28.

• Analysis of glycogen and fat content in skeletal muscle and liver

  Baseline, Day 3 and Day 28

Study Arms (2)

Experimental

ACTIVE COMPARATOR

Dapagliflozin, 10mg, oral dose, once every day

Drug: Dapagliflozin 10 MG [Forxiga]

Control

PLACEBO COMPARATOR

Matching placebo for dapagliflozin, oral dose, once every day

Drug: Dapagliflozin 10 MG [Forxiga]

Interventions

Dapagliflozin 10 MG [Forxiga] DRUG

24 Hour Urine Collection, Sodium (23Na) MRI and Magnetic Resonance (MR) spectroscopy scan, Blood collection for metabolomic and osmolyte analysis

Also known as: Placebo

Control; Experimental

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of heart failure NYHA stage I or II - as shown by their medical records
• Stable anti-hypertensive treatment (\>4 weeks)
• Male and female patients older than 21 years
• Willingness to participate and ability to provide informed consent
• Willingness to use effective birth control if of childbearing potential. Any kind of contraception method will be allowed for the period of the study

You may not qualify if:

• Patients with congestive heart failure NYHA stages I (LVEF \>40%) without type 2 diabetes mellitus.
• Patients with congestive heart failure NYHA stages III and IV
• Prior serious hypersensitivity reaction to Dapagliflozin (Forxiga®)
• 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
• Pregnant and breast-feeding women
• Diagnosis of type 1 diabetes mellitus
• 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.
• 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
• Unstable or rapidly progressing renal disease
• Chronic cystitis and recurrent urinary tract infections
• Impaired renal function with eGFR\<45 ml/min/1.73m2 or proteinuria \> 0.5 g/24h
• Severe hepatic impairment (Child-Pugh class C)
• Any major cardiovascular event/vascular disease within 3 months prior to enrolment, as assessed by the investigator
• Severe edema (as judged by the investigator)
• Active cancer, history of bladder cancer

Sponsors & Collaborators

• National Heart Centre Singapore: lead
• Duke-NUS Graduate Medical School: collaborator

Study Sites (1)

National Heart Centre Singapore

Singapore, 169609, Singapore

Location

Related Publications (1)

• 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.

  PMID: 38599715 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Heart Failure

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study will be a 4-week double blind, placebo-controlled, randomized study with 2 treatment arms.

Study Record Dates

• First Submitted: August 26, 2019
• First Posted: September 6, 2019
• Study Start: November 11, 2019
• Primary Completion: November 10, 2021
• Study Completion: November 10, 2021
• Last Updated: April 13, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)