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.
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
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
Parallel
Vericiguat 10 MG
DrugThe subject will be randomized, in a double-blind manner to vericiguat 10 mg once daily for a period of 12 weeks.
Placebo
Other interventionThe subject will be randomized, in a double-blind manner to placebo once daily for a period of 12 weeks.
Insulin Sensitivity Test
Other interventionAn 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
Other interventionEach participant's Energy Expenditure will be determined using a metabolic cart, at baseline and after 12 weeks of pharmacological interventions.
White Adipose Tissue Biopsy
Other interventionParticipants 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
Other interventionParticipants who consent to participate in the exploratory aim will undergo PET/MR to BAT volume at baseline and after 12 weeks of pharmacological interventions.
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.
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.
Change in BAT volume after vericiguat in Black obese individuals with insulin resistance.
The difference in change in BAT volume between baseline and post-intervention between two arms.
Change in BAT activity after vericiguat in Black obese individuals with insulin resistance.
The difference in change in BAT activity between baseline and post-intervention between two arms.
Change in UCP1 gene expression after vericiguat in Black obese individuals with insulin resistance.
The difference in change in UCP1 gene expression between baseline and post-intervention between two arms.
Change in exercise energy expenditure (EEE) after vericiguat in Black obese individuals with insulin resistance.
The difference in change in EEE between baseline and post-intervention between two arms.
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
