Treating the Endothelium to Restore Insulin Sensitivity

Obesity Clinical Trial

Official title:

Treating the Endothelium to Restore Insulin Sensitivity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00402194
• Other study ID #: IU-IRB-0301-08
• Status: Completed
• Phase: N/A
• First received: November 20, 2006
• Last updated: September 20, 2013
• Start date: June 2005
• Est. completion date: March 2012

Study information

• Verified date: September 2013
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: March 2012
• Est. primary completion date: November 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 55 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glucose Intolerance
• Impaired Glucose Tolerance
• Insulin Resistance
• Obesity
• Pre-diabetes
• Prediabetic State

Intervention

Drug:
• Losartan
Tablet, 100mg, once per day for 3 months

Locations

Country	Name	City	State
United States	Indiana University Hospital GCRC	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Indiana University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Leg Blood Flow Response to Insulin		3 months	No
Primary	Insulin-stimulated Leg Glucose Uptake		3 months	No