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

NCT06320951 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 300012681Pending
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Energy Expenditure; Insulin Sensitivity; African Americans; Cyclic Guanosine Monophosphate

Outcome Measures

Primary Outcomes (2)

• Change in insulin sensitivity after vericiguat in Black obese individuals with insulin resistance.

  The difference in change in insulin sensitivity between baseline and post-intervention between two arms.

  12 weeks

• Change in resting energy expenditure (REE) after vericiguat in Black obese individuals with insulin resistance.

  The difference in change in REE between baseline and post-intervention between two arms.

  12 weeks

Secondary Outcomes (8)

• Change in BAT volume after vericiguat in Black obese individuals with insulin resistance.

  12 weeks

• Change in BAT activity after vericiguat in Black obese individuals with insulin resistance.

  12 weeks

• Change in UCP1 gene expression after vericiguat in Black obese individuals with insulin resistance.

  12 weeks

• Change in exercise energy expenditure (EEE) after vericiguat in Black obese individuals with insulin resistance.

  12 weeks

• Change in glycosylated hemoglobin (HbA1C) after vericiguat in Black obese individuals with insulin resistance.

  12 weeks

Study Arms (2)

Experimental: Vericiguat

EXPERIMENTAL

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

Drug: Vericiguat 10 MG; Other: Insulin Sensitivity Test; Other: Resting Energy and Exercise Energy Expenditure Assessment; Other: White Adipose Tissue Biopsy; Other: MRI-PET Scan for Brown Adipose Tissue Volume Assessment

Placebo

PLACEBO COMPARATOR

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

Other: Placebo; Other: Insulin Sensitivity Test; Other: Resting Energy and Exercise Energy Expenditure Assessment; Other: White Adipose Tissue Biopsy; Other: MRI-PET Scan for Brown Adipose Tissue Volume Assessment

Interventions

Vericiguat 10 MG DRUG

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

Also known as: Vericiguat Arm

Experimental: Vericiguat

Placebo OTHER

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

Also known as: Placebo Arm

Placebo

Insulin Sensitivity Test OTHER

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

Experimental: Vericiguat; Placebo

Resting Energy and Exercise Energy Expenditure Assessment OTHER

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

Also known as: Resting and Exercise Induced Energy Expenditure Test

Experimental: Vericiguat; Placebo

White Adipose Tissue Biopsy OTHER

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.

Experimental: Vericiguat; Placebo

MRI-PET Scan for Brown Adipose Tissue Volume Assessment OTHER

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.

Experimental: Vericiguat; Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults: Age more than or equal to 18 years of age
• Self-identified race/ethnicity as African-American or Black
• BMI ≥ 30 kg/m2
• HOMA-IR ≥ 2.5
• Blood pressure: 120-160/80-100 mmHg (untreated or 1 week of washout in those treated with up to two classes of antihypertensives)
• Willing to adhere to study protocol

You may not qualify if:

• Women who are pregnant or breastfeeding or who can become pregnant and not practicing an acceptable method of birth control during the study (including abstinence)
• Have any past or present history of cardiovascular diseases (stroke, myocardial infarction, heart failure, transient ischemic attack, angina, seizure or cardiac arrhythmia)
• BP more than 160/100 mmHg or those treated with three or more classes of antihypertensives
• BMI \>45 kg/m2
• History of diabetes or fasting plasma glucose \>=126 mg/dL or HbA1C\>=6.5% or prior treatment with antidiabetics
• Estimated GFR \< 60 ml/min/1.73 m2; albumin-creatinine ratio ≥30 mg/g
• Hepatic Transaminase (AST and ALT) levels \>3x the upper limit of normal
• Significant psychiatric illness (assessed using validated MINI questionnaire)
• Anemia (men, Hb\<13 g/dL; women, Hb \<12 g/dL)
• Inability to exercise on a treadmill

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Cardiovascular Diseases; Insulin Resistance; Metabolic Diseases; Obesity

Interventions

vericiguat

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Pankaj Arora, MD, FAHA

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nehal Vekariya, MS

CONTACT

2059347173; nvekariya@uabmc.edu

Naman Shetty, MD

CONTACT

2059755826; nsshetty@uabmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Division of Cardiovasular Disease, Department of Medicine

Study Record Dates

• First Submitted: March 13, 2024
• First Posted: March 20, 2024
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2029
• Last Updated: January 23, 2026

Record last verified: 2026-01

Locations

US (1)