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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Vanderbilt University
Sponsor:
Information provided by (Responsible Party):
Nancy J. Brown, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01409993
First received: July 11, 2011
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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 4

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: Basic Science

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

Age > 18 years and BMI > 25 kg/M2 (> 23 kg/M2 among Asian Americans) Elevated fasting plasma glucose (100-125 mg/dL) IGT (2 hour plasma glucose 140-199 mg/dL) OR metabolic syndrome 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 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01409993

Contacts
Contact: Loretta Byrne, RN 615-322-2105 loretta.byrne@vanderbilt.edu
Contact: Cyndia Shibao, MD 615-936-4584 Cyndya.shibao@vanderbilt.edu

Locations
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37232
Contact: Nancy Brown, MD    615-343-8701    nancy.j.brown@vanderbilt.edu   
Sub-Investigator: Cyndia Shibao, MD         
Sponsors and Collaborators
Vanderbilt University
Investigators
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
ClinicalTrials.gov Identifier: NCT01409993     History of Changes
Other Study ID Numbers: 110206
Study First Received: July 11, 2011
Last Updated: April 30, 2014
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
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Sildenafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on August 26, 2014