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

NCT02129725 | Completed Phase 4 Results DMC

• 1 other identifier: 110206-substudy
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Metabolic Syndrome

Outcome Measures

Primary Outcomes (1)

• Insulin-stimulated AKT Phosphorylation

  measured using Western blot for pAkt and for total Akt from muscle biopsies obtained at the end of the baseline hyperinsulinemic clamp and the three-month hyperglycemic clamp. The ratio of pAkt to Akt expression was calculated at each time point and the change in ratio from 0 to 3 months is presented.

  3 months

Study Arms (2)

sildenafil citrate

EXPERIMENTAL

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

Drug: Sildenafil citrate

placebo oral capsule

PLACEBO COMPARATOR

In the parent study, subjects are randomized to matching placebo

Drug: Placebo Oral Capsule

Interventions

Sildenafil citrate DRUG

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

Also known as: Viagra

sildenafil citrate

Placebo Oral Capsule DRUG

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

Also known as: placebo comparator

placebo oral capsule

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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).

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-6602, United States

Location

MeSH Terms

Conditions

Metabolic Syndrome

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Insulin Resistance; 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: Nancy J. Brown, M.D.
• Organization: Vanderbilt University Medical Center

nancy.j.brown@vanderbilt.edu

615-343-8701

Study Officials

• Nancy J Brown, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Medicine and Pharmacology

Study Record Dates

• First Submitted: April 30, 2014
• First Posted: May 2, 2014
• Study Start: April 1, 2014
• Primary Completion: October 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 19, 2017
• Results First Posted: April 19, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)