Effect of Prolonged PDE-5 Inhibition on Insulin Signaling in Skeletal Muscle.

NCT ID: NCT02129725

Last Updated: 2017-04-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2016-12-31

Brief Summary

Our research proposal will determine if PDE-5 inhibition exerts a favorable effect on insulin signaling pathways in skeletal muscle of subjects with impaired fasting glucose and/or impaired glucose tolerance.

Detailed Description

Participants enrolled in the study titled " Renin-angiotensin and fibrinolysis interaction in humans: effect of long-term PDE5 inhibition on glucose Homeostasis, (Specific aim 2)" will be offered the opportunity to participate in this sub-study.

We will obtain skeletal muscle biopsies from 16 subjects who are enrolled in specific aim 2. Eight subjects will be in the sildenafil group and 8 subjects will be in the placebo group.

Conditions

Metabolic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

sildenafil citrate

In the parent study, subjects are randomized to sildenafil 25 mg tid.

Group Type: EXPERIMENTAL

Sildenafil citrate

Intervention Type: DRUG

Sildenafil citrate 25 mg, 1 capsule three times a day for 3 months

placebo oral capsule

In the parent study, subjects are randomized to matching placebo

Group Type: PLACEBO_COMPARATOR

Placebo Oral Capsule

Intervention Type: DRUG

placebo capsules, 1 capsule po three times a day for 3 months

Interventions

Sildenafil citrate

Sildenafil citrate 25 mg, 1 capsule three times a day for 3 months

Intervention Type: DRUG

Placebo Oral Capsule

placebo capsules, 1 capsule po three times a day for 3 months

Intervention Type: DRUG

Other Intervention Names

Viagra; placebo comparator

Eligibility Criteria

Inclusion Criteria

Age > 18 years and BMI > 25 kg/M2 (> 23 kg/M2 among Asian Americans) and ≤40kg/m2 Impaired fasting glucose (100-125mg/dL) and/or impaired glucose tolerance (2-hr plasma glucose 140-199 mg/dL) and/or hemoglobin A1c 5.7-6.4%

Exclusion Criteria

• Diabetes type 1 or type 2, as defined by a fasting glucose of 126 mg/dL or greater, a two-hour plasma glucose of 200 mg/dL or greater, or the use of anti-diabetic medication.
• The use of nitrates or any disease that might require the use of nitrates.
• The use of any potent CYP3A4 inhibitor.
• Subjects who have participated in a weight-reduction program during the last 6 month or whose weight has increased or decreased more than 2 kg over the preceding 6 months.
• Pregnancy. Women of child-bearing potential will be required to have undergone tubal ligation or to be using barrier or hormonal methods of birth control.
• Breast-feeding.
• Cardiovascular disease such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure, deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy.
• Treatment with anticoagulants.
• Treatment with metformin.
• History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack.
• History or presence of immunological or hematological disorders.
• Diagnosis of asthma on current inhaled corticosteroid therapy.
• Clinically significant gastrointestinal impairment that could interfere with drug absorption.
• Impaired hepatic function (aspartate amino transaminase and/or alanine amino transaminase >1.5 x upper limit of normal range)
• Impaired renal function (serum creatinine >1.5 mg/dl).
• Hematocrit <35%.
• 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).
• Treatment with lithium salts.
• History of alcohol or drug abuse.
• Treatment with any investigational drug in the 1 month preceding the study.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Nancy J. Brown

Professor Medicine and Pharmacology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nancy J Brown, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

110206-substudy

Identifier Type: -

Identifier Source: org_study_id