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Study of Sildenafil Citrate on Insulin Resistance in African American

Sponsor
Vanderbilt University Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT01334554
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH), Pfizer (Industry)
46
Enrollment
1
Location
2
Arms
28
Duration (Months)
1.6
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
46 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Other
Official Title:
Effect of Sildenafil Citrate on Insulin Resistance and Endothelial Function in Obese African American Women
Study Start Date :
Apr 1, 2011
Actual Primary Completion Date :
Aug 1, 2013
Actual Study Completion Date :
Aug 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Sildenafil

Sildenafil 20 mg three times a day

Drug: Sildenafil
20 mg three times a day.
Other Names:
  • Revatio

    		•
    Placebo Comparator: Placebo

    placebo

    Drug: Placebo
    No active drug

    Outcome Measures

    Primary Outcome Measures

    1. Insulin Sensitivity [Insulin sensitivity measured at baseline and 4 weeks after the intervention]

      insulin sensitivity as measured by frequently sampled intravenous glucose tolerance test

    Secondary Outcome Measures

    1. Endothelial Function [Difference between FMD at baseline and 4 weeks]

      Endothelial function was measured with flow mediated dilation, percent change

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Vanderbilt University Nashville Tennessee United States 37232

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Cyndya Shibao, MD, Vanderbilt University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Cyndya Shibao, Assistant Professor of Medicine, Vanderbilt University Medical Center
    ClinicalTrials.gov Identifier:
    NCT01334554
    Other Study ID Numbers:
    • 100713
    • K23HL103976
    First Posted:
    Apr 13, 2011
    Last Update Posted:
    Mar 27, 2017
    Last Verified:
    Feb 1, 2017
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Cyndya Shibao, Assistant Professor of Medicine, Vanderbilt University Medical Center
    African American
    Women
    Metabolic Syndrome
    Endothelial function
    Sildenafil citrate
    Additional relevant MeSH terms:
    Metabolic Syndrome
    Insulin Resistance
    Sildenafil Citrate

    Study Results

    Participant Flow

    Recruitment Details The recruitment started on 03/16/2011 and the first subject was screened on 03/17/2011. Participants were enrolled at Vanderbilt University Medical Center.
    Pre-assignment Detail We screened 132 participants. Eighty six participants were excluded because of the following reasons: 80 did not meet inclusion criteria 5 declined to participate after the screening visit 1 excluded because of difficult intravenous access.
    Arm/Group Title Sildenafil Placebo
    Arm/Group Description Participants received sildenafil citrate 20 mg three times a day in a fasting condition for 4 weeks Participants received placebo three times a day for 4 weeks
    Period Title: Overall Study
    STARTED 23 23
    COMPLETED 19 21
    NOT COMPLETED 4 2

    Baseline Characteristics

    Arm/Group Title Sildenafil Placebo Total
    Arm/Group Description Sildenafil 20 mg three times a day for 4 weeks Placebo three times a day for 4 weeks Total of all reporting groups
    Overall Participants 23 23 46
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    23
    100%
    23
    100%
    46
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    42
    (9.5)
    43
    (10.4)
    42.4
    (9.9)
    Sex: Female, Male (Count of Participants)
    Female
    23
    100%
    23
    100%
    46
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Height (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    164
    (5.2)
    162
    (4.8)
    163
    (5.0)
    Weight (kG) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kG]
    104.5
    (16.7)
    102
    (16.4)
    103.3
    (16.4)
    Body mass index (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    39
    (5.3)
    39
    (5.7)
    39
    (5.4)
    Waist circumference (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    112
    (10.1)
    108
    (11.4)
    110
    (11.0)
    HDL (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    44.0
    (9.9)
    45
    (11.1)
    44
    (10.4)
    triglycerides (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    94.0
    (52.9)
    85
    (48.5)
    89
    (50.5)
    glucose (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    90
    (10.6)
    97
    (11.4)
    93.5
    (11.4)
    insulin (uU/ml) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [uU/ml]
    15
    (7.7)
    14
    (9.9)
    14.6
    (8.7)

    Outcome Measures

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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Sildenafil Placebo
    Arm/Group Description Sildenafil: 20 mg TID Placebo tablets, 1 tablet three times a day
    Measure Participants 19 21
    Baseline
    3.4
    (2.53)
    2.7
    (1.83)
    4-week during intervention
    3.2
    (3.02)
    3.0
    (2.12)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sildenafil, Placebo
    Comments H0= 4-week treatment with sildenafil citrate does not improve insulin sensitivity in obese African American women.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.55
    Comments p- value was unadjusted. Primary outcome underwent logarithmic transformation
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter Beta coefficient (linear regression)
    Estimated Value 0.12
    Confidence Interval (2-Sided) 95%
    -0.33 to 0.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Endothelial Function
    Description Endothelial function was measured with flow mediated dilation, percent change
    Time Frame Difference between FMD at baseline and 4 weeks

    Outcome Measure Data

    Analysis Population Description
    We detected problems with the ultrasound images obtained to measure flow mediated dilation and therefore only data in 14 subjects in the sildenafil group and in 16 subjects in the placebo were analyzed.
    Arm/Group Title Sildenafil Placebo
    Arm/Group Description Sildenafil 20 mg three times a day Sildenafil: 20 mg three times a day. placebo Placebo: No active drug
    Measure Participants 14 16
    Measure percent change of brachial artery diamet 14 16
    Mean (Standard Deviation) [percentage of brachial artery diameter]
    4.7
    (2.9)
    5.3
    (3.1)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sildenafil, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.649
    Comments Adjusted for baseline values only
    Method Regression, Linear
    Comments
    Method of Estimation Estimation Parameter Beta coefficient
    Estimated Value 0.46
    Confidence Interval (2-Sided) 95%
    -1.58 to 2.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame 4 weeks
    Adverse Event Reporting Description
    Arm/Group Title Sildenafil Placebo
    Arm/Group Description Participants received sildenafil citrate 20 mg three times a day in a fasting condition for 4 weeks Participants received placebo three times a day for 4 weeks
    All Cause Mortality
    Sildenafil Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Sildenafil Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/23 (0%) 0/23 (0%)
    Other (Not Including Serious) Adverse Events
    Sildenafil Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 17/23 (73.9%) 14/23 (60.9%)
    Ear and labyrinth disorders
    sinus infection 0/23 (0%) 0 2/23 (8.7%) 2
    General disorders
    flushing 0/23 (0%) 0 2/23 (8.7%) 3
    Musculoskeletal and connective tissue disorders
    back ache 3/23 (13%) 3 2/23 (8.7%) 3
    edema 2/23 (8.7%) 5 0/23 (0%) 0
    Nervous system disorders
    Headaches 12/23 (52.2%) 20 7/23 (30.4%) 10
    dizziness 5/23 (21.7%) 6 1/23 (4.3%) 1
    lightheadedness 3/23 (13%) 3 0/23 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results Point of Contact

    Name/Title Cyndya A. Shibao
    Organization Vanderbilt University Medical Center
    Phone 6159364584
    Email cyndya.shibao@vanderbilt.edu
    Responsible Party:
    Cyndya Shibao, Assistant Professor of Medicine, Vanderbilt University Medical Center
    ClinicalTrials.gov Identifier:
    NCT01334554
    Other Study ID Numbers:
    • 100713
    • K23HL103976
    First Posted:
    Apr 13, 2011
    Last Update Posted:
    Mar 27, 2017
    Last Verified:
    Feb 1, 2017