Improving Cardiometabolic Health in Black Individuals Through Therapeutic Augmentation of Cyclic Guanosine Mono-Phosphate Signaling Pathway
University of Alabama at Birmingham
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.
Description
Obese Black individuals have a higher prevalence of insulin resistance, which is linked to an elevated risk of cardiometabolic diseases and cardiovascular disease. The reasons behind the increased insulin resistance in this group are not fully understood. Key to regulating glucose metabolism and the overall balance of energy, the cyclic guanosine monophosphate (cGMP) pathway is crucial for maintaining cardiometabolic health. Research indicates that both Black race and obesity are associated with reduced levels of upstream regulators of cGMP activity, including natriuretic peptides (NPs) and ni…
Eligibility
- Age range
- 18–80 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * 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 Exclusion Criteria: * 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, myo…
Interventions
- DrugVericiguat 10 MG
The subject will be randomized, in a double-blind manner to vericiguat 10 mg once daily for a period of 12 weeks.
- OtherPlacebo
The subject will be randomized, in a double-blind manner to placebo once daily for a period of 12 weeks.
- OtherInsulin 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.
- OtherResting 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.
- OtherWhite 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.
Location
- University of Alabama at BirminghamBirmingham, Alabama