Renin-Angiotensin and Fibrinolysis in Humans: Effect of Long-Term PDE5 Inhibition on Glucose Homeostasis

This study is currently recruiting participants.
Verified December 2013 by Vanderbilt University
Information provided by (Responsible Party):
Nancy J. Brown, Vanderbilt University Identifier:
First received: July 11, 2011
Last updated: December 26, 2013
Last verified: December 2013

The purpose of this study is to determine the effect of chronic PDE5 inhibitor therapy on glucose metabolism in persons with impaired glucose tolerance.

Condition Intervention Phase
Impaired Glucose Tolerance
Drug: Administration of Sildenafil or Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Resource links provided by NLM:

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • insulin secretion [ Time Frame: 2.5 hours before and after 3 months of therapy ] [ Designated as safety issue: No ]
    in the subjects undergoing hyperglycemic clamp to assess glucose-stimulated insulin secretion

  • glucose infusion rate [ Time Frame: 2.5 hours before and after 3 months of therapy ] [ Designated as safety issue: No ]
    In the group of subjects undergoing euglycemic clamp

Secondary Outcome Measures:
  • fasting plasma glucose [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • blood pressure [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 260
Study Start Date: August 2011
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: sildenafil Drug: Administration of Sildenafil or Placebo
Subjects with IGF will have a baseline hyperglycemic or a euglycemic clamp and then receive sildenafil or placebo for 3 months. Another hyperglycemic or euglycemic clamp will be preformed followed by another 3 months of drug and an oral glucose tolerance test.
Placebo Comparator: placebo Drug: Administration of Sildenafil or Placebo
Subjects with IGF will have a baseline hyperglycemic or a euglycemic clamp and then receive sildenafil or placebo for 3 months. Another hyperglycemic or euglycemic clamp will be preformed followed by another 3 months of drug and an oral glucose tolerance test.


Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion criteria:

  • Age > 18 years
  • Overweight BMI > 25
  • Elevated fasting plasma glucose (100-125 mg/dL)
  • Impaired Fasting Glucose(Two hour plasma glucose 140-199 mg/dL)

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 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 (LV hypertrophy acceptable), 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.
  • Clinically significant gastrointestinal impairment that could interfere with drug absorption.
  • Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino.

transaminase [ALT] >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 the study
  Contacts and Locations
Please refer to this study by its identifier: NCT01409993

Contact: Loretta Byrne, RN 615-322-2105
Contact: Cyndia Shibao, MD 615-936-4584

United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37232
Contact: Nancy Brown, MD    615-343-8701   
Sub-Investigator: Cyndia Shibao, MD         
Sponsors and Collaborators
Vanderbilt University
Principal Investigator: Nancy J Brown, MD Vanderbilt University
  More Information

No publications provided

Responsible Party: Nancy J. Brown, Robert H. Williams Professor of Medicine and Pharmacology, Vanderbilt University Identifier: NCT01409993     History of Changes
Other Study ID Numbers: 110206
Study First Received: July 11, 2011
Last Updated: December 26, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
BMI greater than 25
Elevated fasting blood sugar (100-125mg/dL)

Additional relevant MeSH terms:
Glucose Intolerance
Glucose Metabolism Disorders
Metabolic Diseases
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on April 17, 2014