Clinical trial NCT01409993: Renin-Angiotensin and Fibrinolysis in Humans: Effect of Long-Term PDE5 Inhibition on Glucose Homeostasis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Impaired Glucose Tolerance
Keywords: BMI greater than 25
Elevated fasting blood sugar (100-125mg/dL)
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2011-08-04
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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


Eligibility 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

Primary outcomes:
measure: Insulin Secretion
timeFrame: 2.5 hours after 3 months of therapy
measure: Index of Tissue Sensitivity to Insulin
timeFrame: 2.5 hours after 3 months of therapy
measure: Glucose Infusion Rate
timeFrame: 2.5 hours after 3 months of therapy
Secondary outcomes:
measure: Fasting Plasma Glucose
timeFrame: 3 months
measure: Blood Pressure
timeFrame: 3 months
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: Nancy J Brown, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ramirez CE, Nian H, Yu C, Gamboa JL, Luther JM, Brown NJ, Shibao CA. Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial. J Clin Endocrinol Metab. 2015 Dec;100(12):4533-40. doi: 10.1210/jc.2015-3415. Epub 2015 Nov 18.
citation: Ramirez CE, Shuey MM, Milne GL, Gilbert K, Hui N, Yu C, Luther JM, Brown NJ. Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans. Prostaglandins Other Lipid Mediat. 2014 Oct;113-115:38-44. doi: 10.1016/j.prostaglandins.2014.08.001. Epub 2014 Aug 28.