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CD36 in Nutrient Delivery and Its Dysfunction

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ClinicalTrials.gov Identifier: NCT03012386
Recruitment Status : Active, not recruiting
First Posted : January 6, 2017
Last Update Posted : January 19, 2021
Sponsor:
Collaborator:
Washington University School of Medicine
Information provided by (Responsible Party):
Cyndya Shibao, Vanderbilt University Medical Center

Brief 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.

Condition or disease Intervention/treatment Phase
Insulin Resistance Endothelial Dysfunction Drug: Sildenafil Citrate Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 83 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Role of CD36 in Nutrient Delivery and Its Dysfunction in African Americans
Actual Study Start Date : January 2017
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sildenafil citrate
Sildenafil citrate 20 mg three times a day
Drug: Sildenafil Citrate
phosphodiesterase 5 inhibitor
Other Name: viagra, revatio,




Primary Outcome Measures :
  1. insulin-stimulated microvascular recruitment. [ Time Frame: 4 weeks ]
    The primary endpoint is the change in microvascular blood volume (ΔMBV) during insulin infusion from baseline, an index of insulin-stimulated microvascular recruitment.


Secondary Outcome Measures :
  1. Insulin sensitivity [ Time Frame: 4 weeks ]
    Glucose infusion rate during hyperinsulinemic euglycemic clamp



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria

  • African American men and women.
  • Age 18-50 years
  • BMI 25-40 kg/m2

Exclusion criteria:

  • Diabetes type 1 or type 2, as defined by a FPG > 126 mg/dL a two-hour plasma glucose > 200 mg/dL, or the use of anti-diabetic medication
  • Pulmonary hypertension
  • Use of a PDE5 inhibitor for erectile dysfunction
  • Pregnancy or breast-feeding. Women of child-bearing potential will be required to have undergone tubal ligation or to be using an oral contraceptive or barrier methods of birth control.
  • Cardiovascular disease such as myocardial infarction, presence of angina pectoris, significant arrhythmia, congestive heart failure (left ventricular hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
  • History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack
  • History or presence of immunological or hematological disorders
  • Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
  • Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
  • History of alcohol or drug abuse
  • Mental conditions rendering a subject unable to understand the nature, scope and possible consequences of the study
  • Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, unlikelihood of completing the study, and investigator discretion

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03012386


Locations
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United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University Medical Center
Washington University School of Medicine
Investigators
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Principal Investigator: Cyndya Shibao, MD Vanderbilt University Medical Center
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Responsible Party: Cyndya Shibao, Assistant Professor of Medicine, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT03012386    
Other Study ID Numbers: 160955
First Posted: January 6, 2017    Key Record Dates
Last Update Posted: January 19, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cyndya Shibao, Vanderbilt University Medical Center:
CD36
Endothelial dysfunction
African Americans
Additional relevant MeSH terms:
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Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Sildenafil Citrate
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Urological Agents