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

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ClinicalTrials.gov Identifier: NCT02129725
Recruitment Status : Completed
First Posted : May 2, 2014
Results First Posted : April 19, 2017
Last Update Posted : April 19, 2017
Sponsor:
Information provided by (Responsible Party):
Nancy J. Brown, Vanderbilt University Medical Center

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.

Condition or disease Intervention/treatment Phase
Metabolic Syndrome Drug: Sildenafil citrate Drug: Placebo Oral Capsule Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Renin- Angiotensin and Fibrinolysis Interaction in Humans: Effect of Long-term PDE-5 Inhibition on Glucose Homeostasis. Sub-study
Study Start Date : April 2014
Actual Primary Completion Date : October 2016
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: sildenafil citrate
In the parent study, subjects are randomized to sildenafil 25 mg tid.
Drug: Sildenafil citrate
Sildenafil citrate 25 mg, 1 capsule three times a day for 3 months
Other Name: Viagra

Placebo Comparator: placebo oral capsule
In the parent study, subjects are randomized to matching placebo
Drug: Placebo Oral Capsule
placebo capsules, 1 capsule po three times a day for 3 months
Other Name: placebo comparator




Primary Outcome Measures :
  1. Insulin-stimulated AKT Phosphorylation [ Time Frame: 3 months ]

    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.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02129725


Locations
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United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-6602
Sponsors and Collaborators
Vanderbilt University Medical Center
Investigators
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Principal Investigator: Nancy J Brown, MD Vanderbilt University Medical Center

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Responsible Party: Nancy J. Brown, Professor Medicine and Pharmacology, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT02129725     History of Changes
Other Study ID Numbers: 110206-substudy
First Posted: May 2, 2014    Key Record Dates
Results First Posted: April 19, 2017
Last Update Posted: April 19, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Metabolic Syndrome
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Citric Acid
Sodium Citrate
Sildenafil Citrate
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Urological Agents