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
  Purpose

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.


Condition Intervention
Obesity
Insulin Resistance
Impaired Glucose Tolerance
Pre-diabetes
Drug: Losartan

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treating the Endothelium to Restore Insulin Sensitivity

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • 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 ]

Enrollment: 17
Study Start Date: June 2005
Study Completion Date: March 2012
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Losartan
    Tablet, 100mg, once per day for 3 months
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   20 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00402194

Locations
United States, Indiana
Indiana University Hospital GCRC
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University School of Medicine
Investigators
Principal Investigator: Kieren J Mather, MD Indiana University
  More Information

No publications provided

Responsible Party: Indiana University ( Indiana University School of Medicine )
ClinicalTrials.gov Identifier: NCT00402194     History of Changes
Other Study ID Numbers: IU-IRB-0301-08
Study First Received: November 20, 2006
Results First Received: May 6, 2013
Last Updated: September 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Indiana University:
Obesity
Insulin resistance
Impaired glucose tolerance
pre-diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Insulin Resistance
Obesity
Glucose Intolerance
Prediabetic State
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperinsulinism
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hyperglycemia
Insulin
Losartan
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014