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

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

78 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-08-31

Study Completion Date

2016-11-30

Brief Summary

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

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Detailed Description

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Conditions

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Impaired Glucose Tolerance

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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sildenafil Aim 1

sildenafil 25 mg p.o. tid

Group Type EXPERIMENTAL

Sildenafil

Intervention Type DRUG

Sildenafil 25 mg by mouth three times a day for three months

Hyperglycemic clamp

Intervention Type DIAGNOSTIC_TEST

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

placebo Aim 1

matching placebo p.o. tid

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching placebo three times a day for three months

Hyperglycemic clamp

Intervention Type DIAGNOSTIC_TEST

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

sildenafil Aim 2

sildenafil 25 mg p.o. tid

Group Type EXPERIMENTAL

Sildenafil

Intervention Type DRUG

Sildenafil 25 mg by mouth three times a day for three months

Euglycemic clamp

Intervention Type DIAGNOSTIC_TEST

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

placebo Aim 2

matching placebo p.o. tid

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching placebo three times a day for three months

Euglycemic clamp

Intervention Type DIAGNOSTIC_TEST

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

Interventions

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Sildenafil

Sildenafil 25 mg by mouth three times a day for three months

Intervention Type DRUG

Placebo

Matching placebo three times a day for three months

Intervention Type DRUG

Hyperglycemic clamp

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

Intervention Type DIAGNOSTIC_TEST

Euglycemic clamp

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

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No