VITAL-IMPACT: Improving Cardiometabolic Health in Black Individuals Through Therapeutic Augmentation of Cyclic Guanosine Mono-Phosphate Signaling Pathway

Summary

This study investigates the potential of vericiguat, a soluble guanylate cyclase stimulator, to improve cardiometabolic health in obese Black individuals with insulin resistance by directly enhancing cyclic guanosine monophosphate (cGMP) activity. Given that this population has been shown to have lower cGMP activity and the association of lower cGMP activity with increased cardiometabolic disease risk, the proposed study hypothesizes that augmenting cGMP activity in obese individuals will improve insulin sensitivity and energy expenditure. This study is a placebo-controlled randomized trial involving 200 Black obese participants with insulin resistance, assessing the effects of vericiguat on insulin sensitivity, resting, and exercise-induced energy expenditure over 12 weeks. Additionally, it will explore changes in brown adipose tissue and gene expression related to energy metabolism in white adipose tissue, aiming to provide insights into how increasing cGMP activity may improve cardiometabolic health in Black obese individuals.

Conditions

• Cardiovascular Diseases
• Insulin Sensitivity/Resistance
• Metabolic Disease
• Metabolism
• Energy Expenditure
• Obesity

Interventions

OTHER

Resting Energy and Exercise Energy Expenditure Assessment

Each participant's Energy Expenditure will be determined using a metabolic cart, at baseline and after 12 weeks of pharmacological interventions.

DRUG

Vericiguat 10 MG

The subject will be randomized, in a double-blind manner to vericiguat 10 mg once daily for a period of 12 weeks.

OTHER

Placebo

The subject will be randomized, in a double-blind manner to placebo once daily for a period of 12 weeks.

OTHER

Insulin Sensitivity Test

An assessment of the insulin sensitivity will be done using the Euglycemic Hyperinsulinemic Clamp, at baseline and after 12 weeks of pharmacological interventions.

OTHER

White Adipose Tissue Biopsy

Participants who consent to participate in the exploratory aim will undergo WAT biopsy to assess UCP1 gene expression from the collected biospecimens, at baseline and after 12 weeks of pharmacological interventions.

OTHER

MRI-PET Scan for Brown Adipose Tissue Volume Assessment

Participants who consent to participate in the exploratory aim will undergo PET/MR to BAT volume at baseline and after 12 weeks of pharmacological interventions.

Sponsors & Collaborators

• University of Alabama at Birmingham

  lead OTHER

Principal Investigators

• Pankaj Arora, MD, FAHA · University of Alabama at Birmingham

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-12-01

Primary Completion

2028-04-30

Completion

2029-04-30

FDA Drug

Yes

Countries

• United States

Study Locations