Study of Sildenafil Citrate on Insulin Resistance in African American

Effect of Sildenafil Citrate on Insulin Resistance and Endothelial Function in Obese African American Women

Obesity has a greater detrimental impact on the health of African American women than on any other racial or gender group. Nearly 80% of African American women are overweight or obese in the United States. Hypertension and insulin resistance are more prevalent among African American women as compared to men and Caucasians. These conditions put them at increased risk for the development of diabetes mellitus and cardiovascular disease.

Recent studies have reported that a substance named Nitric Oxide (NO)may have some beneficial effect on how the body handles blood sugar and blood pressure. Of interest,some studies have shown that African Americans have decreased function of NO in their blood vessels.

In this study proposal the investigators will test if increasing NO function with a PDE-5 inhibitor (sildenafil citrate) will improve pre-diabetes and the health of the inner layer of the blood vessels in obese African American women.

Study Overview

• Status: Completed
• Conditions: Obesity; Metabolic Syndrome
• Intervention / Treatment: Drug: Sildenafil; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Race will be self-defined, but only subjects who report both parents of the same race will be included.
• Age 18-60 years old.
• The investigators will recruit subjects with wide range of BMI 30-45 kg/m2.
• Subjects who have metabolic syndrome or who have a fasting insulin >13. The diagnosis include 3 of the following:

Fasting blood glucose of greater than 100 Triglyceride levels of greater than 150 HDL cholesterol of less than 50 in women Blood pressure of at least 130/85, or on blood pressure medicine Waist girth of more than 35 inches in women. Subjects of childbearing potential will be required to have a negative serum/urine pregnancy test. In addition, they will be asked to use a reliable contraceptive method prior to enrollment as determined by the PI (Dr. Cyndya Shibao).

Exclusion Criteria:

• Previous allergic reactions to any of the study medication (sildenafil) or inability to take study medications as prescribed during the course of the study.
• Type 1 or 2 diabetes mellitus as defined by a fasting glucose of 126 mg/dl or greater.
• Use of antidiabetic medication (insulin, metformin, sulfonylurea, troglitazone)
• Cardiovascular disease such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy.
• Current smokers.
• Significant weight change >5% from baseline in the past three months.
• Pregnancy or breast-feeding.
• History of serious neurological disease such as cerebral hemorrhage stroke, transient ischemic attack.
• History or presence of immunological or hematological disorders.
• Clinical significant gastrointestinal impairment that could interfere with drug absorption.
• Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino transaminase [ALT] >1.5X upper limit of normal range).
• Impaired renal function (estimated glomerular filtration rate (eGFR) of <60mL/min).
• 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.
• History of alcohol or drug abuse.
• Mental conditions rendering the 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, and unlikelihood of completing the study.
• Patients must not be taking nitratest in any form (e.g., nitroglycerin, isosorbide dinitrate, nitroprusside, and others) during this study
• Patients on alpha-blocking drugs (doxazosin, terazosin , or prazosin) will be excluded
• Patients on protease inhibitors (ritonavir and others) will be excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; placebo	Drug: Placebo; No active drug
Experimental: Sildenafil; Sildenafil 20 mg three times a day	Drug: Sildenafil; 20 mg three times a day.; Other Names: Revatio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Sensitivity	insulin sensitivity as measured by frequently sampled intravenous glucose tolerance test	Insulin sensitivity measured at baseline and 4 weeks after the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelial Function	Endothelial function was measured with flow mediated dilation, percent change	Difference between FMD at baseline and 4 weeks

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Pfizer
• Investigators: Principal Investigator: Cyndya Shibao, MD, Vanderbilt University

Publications and helpful links

General Publications

• Marinos A, Celedonio JE, Ramirez CE, Gottlieb J, Gamboa A, Hui N, Yu C, Stein CM, Biaggioni I, Shibao CA. Time-Course Analysis of Flow Mediated Dilation for the Evaluation of Endothelial Function After a High-Fat Meal in African Americans. J Am Heart Assoc. 2015 Nov 5;4(11):e002388. doi: 10.1161/JAHA.115.002388.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: April 11, 2011
• First Submitted That Met QC Criteria: April 12, 2011
• First Posted (Estimate): April 13, 2011

Study Record Updates

• Last Update Posted (Actual): March 27, 2017
• Last Update Submitted That Met QC Criteria: February 22, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Women; Metabolic Syndrome; Endothelial function; African American; Sildenafil citrate
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Metabolic Syndrome; Insulin Resistance; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: 100713; K23HL103976 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO