Study of Sildenafil Citrate on Insulin Resistance in African American

NCT01334554 | Completed Phase 1 Results DMC

• 2 other identifiers: 100713K23HL103976
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metabolic Syndrome; Obesity

Keywords

African American; Women; Metabolic Syndrome; Endothelial function; Sildenafil citrate

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Endothelial Function

  Difference between FMD at baseline and 4 weeks

Study Arms (2)

Sildenafil

EXPERIMENTAL

Sildenafil 20 mg three times a day

Drug: Sildenafil

Placebo

PLACEBO COMPARATOR

placebo

Drug: Placebo

Interventions

Sildenafil DRUG

20 mg three times a day.

Also known as: Revatio

Sildenafil

Placebo DRUG

No active drug

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Pfizer: collaborator

Study Sites (1)

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• 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.

  PMID: 26541392 DERIVED

MeSH Terms

Conditions

Metabolic Syndrome; Obesity

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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 A. Shibao
• Organization: Vanderbilt University Medical Center

cyndya.shibao@vanderbilt.edu

6159364584

Study Officials

• Cyndya Shibao, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: April 11, 2011
• First Posted: April 13, 2011
• Study Start: April 1, 2011
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: March 27, 2017
• Results First Posted: April 10, 2015

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)