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

Impaired Glucose Tolerance Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01409993
• Other study ID #: 110206
• Status: Recruiting
• Phase: Phase 4
• First received: July 11, 2011
• Last updated: October 28, 2016
• Start date: August 2011

Study information

• Verified date: October 2016
• Source: Vanderbilt University
• Contact: Patricia Wright, RN
• Phone: 615-322-8837
• Email: patricia.wright[@]vanderbilt.edu
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Glucose Intolerance
• Impaired Glucose Tolerance

Intervention

Drug:
• Administration of Sildenafil or Placebo
Subjects with prediabetes will have a baseline hyperglycemic (Aim 1) or a euglycemic (Aim 2) and then receive sildenafil or placebo for 3 months. Another hyperglycemic or euglycemic clamp will be performed followed by another 3 months off drug and an oral glucose tolerance test.

Locations

Country	Name	City	State
United States	Vanderbilt University	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	insulin secretion	in the group of subjects undergoing hyperglycemic clamp	2.5 hours before and after 3 months of therapy	No
Primary	index of tissue sensitivity to insulin	in the group of subjects undergoing hyperglycemic clamp	2.5 hours before and after 3 months of therapy	No
Primary	glucose infusion rate	In the group of subjects undergoing euglycemic clamp	2.5 hours before and after 3 months of therapy	No
Secondary	fasting plasma glucose		3 months	No
Secondary	blood pressure		3 months	Yes