CD36 in Nutrient Delivery and Its Dysfunction

NCT03012386 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 160955
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Insulin Resistance; Endothelial Dysfunction

Keywords

CD36; Endothelial dysfunction; African Americans

Outcome Measures

Primary Outcomes (2)

• Change in Microvascular Blood Volume (MBV) During Insulin Infusion

  Insulin induces microvascular recruitment. Changes in MBV during Insulin infusion signifies insulin sensitivity. MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a hyperinsulinaemic euglycaemic (HIE) clamp (insulin infusion rate up to 80 mU/m2.min-1 ). In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).

  Baseline to end of procedure (approximately 180 minutes)

• Change in Microvascular Blood Volume (MBV) During Insulin Infusion After 4 Weeks of Sildenafil Treatment in Both Groups

  Chronic treatment with sildenafil increases vascularity and muscle glucose uptake. Changes in MBV during Insulin infusion signifies insulin sensitivity . Insulin sensitivity was tested after 4 weeks of treatment with Sildenafil in both groups. Subjects receive IV infusion of 20% Intralipid (45ml/h) and heparin (200 units/hr). MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a HIE clamp (insulin infusion rate up to 80 mU/m2.min-1 ) In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).

  Baseline to 4 weeks

Study Arms (1)

Sildenafil citrate

EXPERIMENTAL

Sildenafil citrate 20 mg three times a day

Drug: Sildenafil Citrate in G allele carrier; Drug: Sildenafil Citrate in non G allele carrier

Interventions

Sildenafil Citrate in G allele carrier DRUG

chronic use of phosphodiesterase 5 inhibitor in G allele carrier

Also known as: viagra, revatio,

Sildenafil citrate

Sildenafil Citrate in non G allele carrier DRUG

chronic use of phosphodiesterase 5 inhibitor in Non G allele carrier

Also known as: viagra, revatio

Sildenafil citrate

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Washington University School of Medicine: collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Shibao CA, Peche VS, Pietka TA, Samovski D, Williams IM, Abumrad NN, Gamazon ER, Goldberg IJ, Wasserman DH, Abumrad NA. Microvascular insulin resistance with enhanced muscle glucose disposal in CD36 deficiency. Diabetologia. 2025 Mar;68(3):662-675. doi: 10.1007/s00125-024-06292-4. Epub 2024 Nov 6.

  PMID: 39503770 DERIVED

MeSH Terms

Conditions

Insulin Resistance

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Cyndya Shibao MD
• Organization: Vanderbilt University Medical Center

cyndya.shibao@vumc.org

6159364584

Study Officials

• Cyndya Shibao, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: January 3, 2017
• First Posted: January 6, 2017
• Study Start: January 1, 2017
• Primary Completion: July 1, 2021
• Study Completion: July 31, 2021
• Last Updated: November 30, 2022
• Results First Posted: November 30, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)