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

This study has been terminated.
(Aim 1 was stopped by DSMB. Aim 2 was stopped due to ending of funding.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01409993
First Posted: August 4, 2011
Last Update Posted: April 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Nancy J. Brown, Vanderbilt University
July 11, 2011
August 4, 2011
December 7, 2016
April 17, 2017
April 17, 2017
August 2011
November 2016   (Final data collection date for primary outcome measure)
  • Insulin Secretion [ Time Frame: 2.5 hours after 3 months of therapy ]
    in the group of subjects undergoing hyperglycemic clamp (Aim 1)
  • Index of Tissue Sensitivity to Insulin [ Time Frame: 2.5 hours after 3 months of therapy ]
    in the group of subjects undergoing hyperglycemic clamp (Aim 1), calculated by dividing the average glucose infusion rate during the last hour of the clamp by the average plasma insulin concentration during the same interval
  • Glucose Infusion Rate [ Time Frame: 2.5 hours after 3 months of therapy ]
    In the group of subjects undergoing euglycemic clamp (Aim 2)
  • plasma glucose [ Time Frame: 2.5 hours ]
  • plasma insulin [ Time Frame: 2.5 hours ]
Complete list of historical versions of study NCT01409993 on ClinicalTrials.gov Archive Site
  • Fasting Plasma Glucose [ Time Frame: 3 months ]
  • Blood Pressure [ Time Frame: 3 months ]
    Systolic blood pressure
Not Provided
Not Provided
Not Provided
 
Renin-Angiotensin and Fibrinolysis in Humans: Effect of Long-Term PDE5 Inhibition on Glucose Homeostasis
Not Provided
The purpose of this study is to determine the effect of chronic PDE5 inhibitor therapy on glucose metabolism in persons with prediabetes.
Not Provided
Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Impaired Glucose Tolerance
  • Drug: Sildenafil
    Sildenafil 25 mg by mouth three times a day for three months
  • Drug: Placebo
    Matching placebo three times a day for three months
  • Diagnostic Test: 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.
  • 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.
  • Experimental: sildenafil Aim 1
    sildenafil 25 mg p.o. tid
    Interventions:
    • Drug: Sildenafil
    • Diagnostic Test: Hyperglycemic clamp
  • Placebo Comparator: placebo Aim 1
    matching placebo p.o. tid
    Interventions:
    • Drug: Placebo
    • Diagnostic Test: Hyperglycemic clamp
  • Experimental: sildenafil Aim 2
    sildenafil 25 mg p.o. tid
    Interventions:
    • Drug: Sildenafil
    • Diagnostic Test: Euglycemic clamp
  • Placebo Comparator: placebo Aim 2
    matching placebo p.o. tid
    Interventions:
    • Drug: Placebo
    • Diagnostic Test: Euglycemic clamp

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
78
November 2016
November 2016   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01409993
110206
Yes
Not Provided
Not Provided
Nancy J. Brown, Vanderbilt University
Vanderbilt University
Not Provided
Principal Investigator: Nancy J Brown, MD Vanderbilt University
Vanderbilt University Medical Center
March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP