NCT03012386

CD36 in Nutrient Delivery and Its Dysfunction

Role of CD36 in Nutrient Delivery and Its Dysfunction in African Americans

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 26 (actual)
• Sponsor: Vanderbilt University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

This proposal will test the hypothesis that chronic treatment with sildenafil with and without the use of nitric oxide substrate, L-arginine, protects against fatty acid induced impairment of endothelial function, improves insulin-stimulated microvascular recruitment, insulin sensitivity and glucose uptake in CD36 rs3211938 G-allele carriers.

Detailed description

Subjects carrying the G-allele of CD36 coding SNP rs3211938 that results in 50% reduction of CD36 levels in \~25% of African Americans have endothelial dysfunction. Endothelial dysfunction results in impairment of insulin's vascular actions and eventually reduced insulin sensitivity. Insulin induces microvascular recruitment via stimulation of nitric oxide(NO)-cGMP pathway, which facilitates nutrient flux, e.g., glucose to skeletal muscle. Elevated fatty acids impair insulin-stimulated microvascular recruitment and reduce insulin sensitivity. Chronic treatment with sildenafil increases vascularity and muscle glucose uptake in high fat fed mice. In humans, Drs. Shibao (PI) recently reported that a 3-month treatment with sildenafil improves insulin sensitivity in patients with impaired glucose tolerance. More relevant to this project, endothelial dysfunction improved after 4-week treatment with sildenafil in G-allele carriers. This proposal will test the hypothesis that chronic treatment with sildenafil with and without the use of NO substrate, L-arginine, protects against fatty acids induced impairment of endothelial function, improves insulin-stimulated microvascular. The protocol design was changed to single arm design.

Conditions

• Insulin Resistance
• Endothelial Dysfunction

Interventions

Type	Name	Description
DRUG	Sildenafil Citrate in G allele carrier	chronic use of phosphodiesterase 5 inhibitor in G allele carrier
DRUG	Sildenafil Citrate in non G allele carrier	chronic use of phosphodiesterase 5 inhibitor in Non G allele carrier

Timeline

• Start date: 2017-01-01
• Primary completion: 2021-07-01
• Completion: 2021-07-31
• First posted: 2017-01-06
• Last updated: 2022-11-30
• Results posted: 2022-11-30

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study