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

Vanderbilt University

Status and phase: Terminated; Phase 4

Conditions: Impaired Glucose Tolerance

Treatments: Drug: Placebo; Diagnostic Test: Hyperglycemic clamp; Drug: Sildenafil; Diagnostic Test: Euglycemic clamp

Study type: Interventional

Funder types: Other

Identifiers

NCT01409993

110206

Details and patient eligibility

About

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

Enrollment: 78 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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78 participants in 4 patient groups, including a placebo group

sildenafil Aim 1

Experimental group

Description:

sildenafil 25 mg p.o. tid

Treatment:

Diagnostic Test: Hyperglycemic clamp

Drug: Sildenafil

placebo Aim 1

Placebo Comparator group

Description:

matching placebo p.o. tid

Treatment:

Drug: Placebo

Diagnostic Test: Hyperglycemic clamp

sildenafil Aim 2

Experimental group

Description:

sildenafil 25 mg p.o. tid

Treatment:

Drug: Sildenafil

Diagnostic Test: Euglycemic clamp

placebo Aim 2

Placebo Comparator group

Description:

matching placebo p.o. tid

Treatment:

Drug: Placebo

Diagnostic Test: Euglycemic clamp