Treating the Endothelium to Restore Insulin Sensitivity

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Indiana University ( Indiana University School of Medicine )
ClinicalTrials.gov Identifier:
NCT00402194
First received: November 20, 2006
Last updated: September 20, 2013
Last verified: September 2013

November 20, 2006
September 20, 2013
June 2005
November 2011   (final data collection date for primary outcome measure)
  • Leg Blood Flow Response to Insulin [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Insulin-stimulated Leg Glucose Uptake [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • leg blood flow response to insulin
  • insulin-stimulated leg glucose uptake
Complete list of historical versions of study NCT00402194 on ClinicalTrials.gov Archive Site
Not Provided
  • insulin-stimulated whole body glucose uptake
  • leg blood flow response to methacholine chloride
  • leg blood flow response to L-NMMA
Not Provided
Not Provided
 
Treating the Endothelium to Restore Insulin Sensitivity
Treating the Endothelium to Restore Insulin Sensitivity

A study of 12 weeks' treatment with losartan or placebo, to test the hypothesis that RAS inhibition will improve insulin' vascular actions and therefore improve insulin sensitivity in skeletal muscle.

Recent studies suggesting an effect of cardiovascular therapies to prevent diabetes remain unexplained. We hypothesize that these therapies improve vascular endothelial function allowing improved actions of insulin in the vasculature, which comprise a significant portion of insulin's metabolic action. We therefore propose to measure insulin-mediated glucose disposal and insulin-mediated vasodilation before and after 12 weeks' therapy with Losartan (an angiotensin receptor blocker) or placebo, in a randomized design. Subjects will include 28 subjects with impaired glucose tolerance, which is generally accompanied by both insulin resistance and impaired vascular function. With this number of participants we have a 90% chance of showing a statistically significant and clinically meaningful effect of insulin on leg vascular resistance, and an even higher chance of showing a difference in insulin's metabolic effects. Exclusion criteria will include frank hypertension, diabetes, or hypercholesterolemia, and biochemical or other contraindications to losartan therapy. The primary endpoint for statistical analysis will be the invasive measure of insulin-stimulated endothelial function. We anticipate an improvement in both vascular and metabolic measures of insulin action following Losartan therapy but no change from untreated baseline following placebo.

Interventional
Not Provided
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Obesity
  • Insulin Resistance
  • Impaired Glucose Tolerance
  • Pre-diabetes
Drug: Losartan
Tablet, 100mg, once per day for 3 months
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
17
March 2012
November 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Healthy
  • Age 20-55
  • Male and female
  • Obese, defined as Males: BMI >28 or > 30% fat by DEXA scan or Bod Pod; Females: BMI >30 or > 33% fat by DEXA scan or Bod Pod
  • Weight stable over at least 4 months

Exclusion Criteria:

  • Diabetes mellitus (ADA criteria)
  • Age <20 or > 55 yrs
  • Blood pressure >160/90 or < 90/65 mmHg
  • Total cholesterol >240 or LDL cholesterol >160 mg/dL
  • Baseline elevations in AST or ALT > 3X ULN
  • Baseline elevation in creatinine >1.6 ng/mL
  • Unexplained baseline elevation in creatine kinase > 3X ULN
  • Concurrent significant chronic medical illness including, but not limited to, human immunodeficiency virus infection, Syphilis, hepatitis B infection, or hepatitis C infection
  • Pregnancy
  • Known hypersensitivity or intolerance to the study agents
Both
20 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00402194
IU-IRB-0301-08
Yes
Indiana University ( Indiana University School of Medicine )
Indiana University School of Medicine
Not Provided
Principal Investigator: Kieren J Mather, MD Indiana University
Indiana University
September 2013

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