What this study is
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.
What's being tested
- Vericiguat 10 MG
Intervention · DRUG
The subject will be randomized, in a double-blind manner to vericiguat 10 mg once daily for a period of 12 weeks.
- Placebo
Intervention · OTHER
The subject will be randomized, in a double-blind manner to placebo once daily for a period of 12 weeks.
- Insulin Sensitivity Test
Intervention · OTHER
An assessment of the insulin sensitivity will be done using the Euglycemic Hyperinsulinemic Clamp, at baseline and after 12 weeks of pharmacological interventions.
- Resting Energy and Exercise Energy Expenditure Assessment
Intervention · OTHER
Each participant's Energy Expenditure will be determined using a metabolic cart, at baseline and after 12 weeks of pharmacological interventions.
- White Adipose Tissue Biopsy
Intervention · 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.
- MRI-PET Scan for Brown Adipose Tissue Volume Assessment
Intervention · 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.
Study details
- Official title
- Improving Cardiometabolic Health in Black Individuals Through Therapeutic Augmentation of Cyclic Guanosine Mono-Phosphate Signaling Pathway
- Sponsor
- University of Alabama at Birmingham
- Conditions
- Cardiovascular Diseases · Insulin Sensitivity/Resistance · Metabolic Disease · Metabolism · Energy Expenditure · Obesity
- Enrolling
- 200 people
- Starts
- 2026-12-01
- Est. completion
- 2029-04-30
- Design
- Quadruple-blind, randomized, parallel groups, Phase 2
- Record
- View on ClinicalTrials.gov ↗
Who can join
Age 18 Years – 80 YearsSex ALLHealthy volunteers AcceptedYou 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 can't join 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
Sign in and we'll check these against your records.Full criteria on ClinicalTrials.gov ↗
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Study locations (1)
1 openUniversity of Alabama at Birmingham
Birmingham, Alabama, United States
Study team
Sponsor
University of Alabama at Birmingham
Study ID 300012681
Principal investigator
Pankaj Arora, MD, FAHA
University of Alabama at Birmingham
Frequently asked questions
The sponsor hasn't published answers to common questions for this trial.