Dapagliflozin in Reducing Epicardial Adipose Tissue in Heart Failure with Preserved Ejection Fraction

NCT06510270 | Not Yet Recruiting DMC

• 1 other identifier: 865/11/23
• Study Type: interventional
• Target: 70
• Locations: 0 countries
• Sites: N/A

Brief Summary

Heart failure with preserved ejection fraction (HFpEF) is becoming the most common cause of heart failure worldwide, in part, driven by a rising prevalence of obesity. Although generalized and visceral adiposity is important in the pathogenesis of obesity-related HFpEF, there is increasing recognition of the potential role of epicardial adipose tissue (EAT) in disease pathogenesis. EAT is metabolically active tissue located directly on the surface of the myocardium underneath the visceral pericardium. By virtue of its anatomical interface with the heart and the lack of fascial separation between the underlying myocardium and epicardial fat, locally secreted adipokines directly bathe the surface of the heart and result in underlying myocardial remodeling. Its position on the surface of the myocardium allows EAT to directly contribute to an increase in total heart size with stretch of the pericardium and results in relative pericardial restraint with constrictive physiology. EAT is most commonly measured by echocardiography in the parasternal long axis view perpendicular to the right ventricle (RV) to quantify epicardial fat thickness and this has been correlated with worse haemodynamic derangements and adverse outcomes in HFpEF. Alternatively, cardiac MRI or CT can provide a more complete volumetric assessment of epicardial fat volume and has also demonstrated associations with adverse outcomes and functional metrics in most but not all HFpEF studies. Very little is understood about the impact of medical modulation of epicardial fat in HFpEF. The first proven agents to improve heart failure hospitalization and quality of life in HFpEF are the sodium-glucose cotransporter-2 inhibitors (SGLT2i) Although the mechanisms of benefit of these drugs are uncertain, they have demonstrated a reduction in epicardial fat despite only minimal weight loss suggesting a direct lipolytic effect on epicardial fat. The use of SGLT2i has also been associated with reduced incident AF, which may, in part, be due to the reduction in epicardial fat. The diuretic effect of SGLT2i may facilitate a reduction in plasma volume and mechanistic studies have shown that they also promote ventricular mass regression, which may cumulatively decrease pericardial restraint. By this work we aims To determine whether the addition of 10 mg of Dapagliflozin to a patient with HFPEF can lead to a decrease in epicardial adipose tissue volume, which is a new approach to managing HFPEF or not.

Conditions

Heart Failure with Preserved Ejection Fraction

Keywords

HFpEF, Dapagliflozin, epicardial adipose tissue

Outcome Measures

Primary Outcomes (1)

• Reduction in Epicardial adipose tissue volume

  epicardial adipose tissue volume (gm) will be measured by using CMR before starting Dapagliflozin in sympotomatic heart failure group and 6 months latter. In asymptomatic diastolic dysfunction CMR will be performed at enrollment and 6 month latter

  from enrollment (before stsrting dapagliflozin) to 6 month (while still on dapagliflozin)

Secondary Outcomes (3)

• Change in Body mass index

  At enrollement till 6 months latter

• Recurrent hospital admission by heart failure

  From enrollement till 6 months latter

• Cardio-vascular mortality

  From enrollement till 6 months latter

Study Arms (2)

Symptomatic heart failure

ACTIVE COMPARATOR

Patients with clinical manifictations of heart failure but preserved ejection fraction by echocardiography.

Drug: Dapagliflozin 10 mg once daily; Drug: Loop diuretics; Drug: Treatments of associated co-morbidities (e.g Anti-hypertensive, oral hypoglycemic)

Asymptomatic Diastolic dysfunction

PLACEBO COMPARATOR

Patients with diastolic dysfunction grade II or more by Echocardiography but with out any heart failure manifictation.

Drug: Treatments of associated co-morbidities (e.g Anti-hypertensive, oral hypoglycemic)

Interventions

Dapagliflozin 10 mg once daily DRUG

Dapagliflozin 10 mg once daily will be given to all patients in symptomstic heart failure group

Symptomatic heart failure

Loop diuretics DRUG

Loop diuretics (IV or orally) will be given to all patients in symptomatic heart failure group

Symptomatic heart failure

Treatments of associated co-morbidities (e.g Anti-hypertensive, oral hypoglycemic) DRUG

Treatment of associated co-morbidities will be given to both arms (group) such as anti-hypertensive (B blockers, ACIE, ARBS, CA channel blockers, Diuretics), oral hypoglycemic (Metformins, sulfonyl urea,.......)

Asymptomatic Diastolic dysfunction; Symptomatic heart failure

Eligibility Criteria

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

You may qualify if:

• Age \>18 years.
• Patients with established diagnosis of HFpEF: (1. Signs and Symptoms of Heart Failure. 2. Preserved Ejection Fraction (EF): EF greater than or equal to 50% is generally considered preserved. 3.Echo-cardiography: Evidence of left ventricular hypertrophy (LVH) or Evidence of diastolic dysfunction, such as impaired relaxation or increased stiffness of the left ventricle. 4.Elevated Natriuretic Peptides: serum N-terminal pro-B type natriuretic peptide (NT-proBNP) ≥400 pg/mL or brain natriuretic peptide ≥100 pg/mL can support the diagnosis of HFpEF in the presence of symptoms and other findings).
• BMI \>27Kg/m2.
• Adequate follow-up: Participants must be willing and able to comply with the study protocol and follow-up requirements.

You may not qualify if:

• \. Age \<18 years. 2. Type 1 diabetes: Exclude individuals with type 1 diabetes, as dapagliflozin is primarily used for type 2 diabetes management.
• \. Significant renal impairment: Exclude participants with severe renal impairment or end-stage renal disease.
• \. Severe hepatic impairment: Exclude participants with severe hepatic dysfunction.
• \. Pregnancy or breastfeeding: Exclude pregnant or lactating individuals. 6. Patients who underwent Bariateric surgery. 7. BMI\<27Kg/m2. 8. Other serious medical conditions: Exclude participants with serious medical conditions that could interfere with the study or confound the results (e.g., cancer, severe infections).
• \. Inability to comply: Exclude participants who are unable or unwilling to comply with the study procedures and requirements.

Sponsors & Collaborators

• Aswan University: lead

MeSH Terms

Interventions

dapagliflozin; Sodium Potassium Chloride Symporter Inhibitors; Hypoglycemic Agents

Intervention Hierarchy (Ancestors)

Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Diuretics; Natriuretic Agents; Physiological Effects of Drugs

Central Study Contacts

Aml Mohammed Soliman, M.D

CONTACT

+21140898257; aml.mohamed@aswu.edu.eg

Ayman Maher Ashm, M.D

CONTACT

+21011615437; Ayman.asham@yahoo.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of cardiology

Study Record Dates

• First Submitted: July 15, 2024
• First Posted: July 19, 2024
• Study Start: August 1, 2024
• Primary Completion: August 1, 2025
• Study Completion: October 1, 2025
• Last Updated: July 19, 2024

Record last verified: 2024-07