Angiotensin II Blockade and Inflammation in Obesity
Information source: Virginia Polytechnic Institute and State University
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Overweight; Obese; Prehypertension; Hypertension
Intervention: Olmesartan medoxomil (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Virginia Polytechnic Institute and State University Official(s) and/or principal investigator(s): Kevin P. Davy, Ph.D., Principal Investigator, Affiliation: Virginia Polytechnic Institute and State University
Summary
Overweight and obesity, which afflicts ~65% of the U. S. population and more than 1 billion
people worldwide, increases the risk of developing hypertension. Activation of the renin
angiotensin system (RAS) is an important mechanism by which obesity leads to hypertension.
In addition to its vasoconstricting and sodium retaining actions, angiotensin II also has
potent pro-inflammatory actions including macrophage infiltration and expression of
proinflammatory cytokines in target tissues. Adipose tissue and skeletal muscle appear to be
a key sites for the generation of proinflammatory cytokines. Although angiotensin II
receptor blockade reduces inflammation in many tissues, the effects on adipose tissue and
skeletal muscle in humans are not clear. Importantly, the chronic low grade inflammatory
state that accompanies obesity complicates hypertension by contributing to insulin
resistance and accelerating cardiovascular disease. Therefore, the general aim of the
present proposal will be to determine the influence of angiotensin II receptor blockade on
adipose tissue and skeletal muscle inflammation and its relation to improvements in insulin
sensitivity, if observed, in obese hypertensive humans. To address these aims, 44 obese
(BMI>30 kg/m2) hypertensive (BP>140 systolic and/or 90 diastolic) individuals (age=50-65
years) will be randomized to receive 8 weeks of either the angiotensin II receptor
antagonist, olmesartan medoxomil, or no treatment in a crossover manner. Subcutaneous
adipose tissue and skeletal muscle biopsies will be obtained and insulin sensitivity
(intravenous glucose tolerance tests) will be assessed at baseline and following 8 weeks of
each intervention. A two week washout period will separate the interventions.
Clinical Details
Official title: Angiotensin II Blockade and Adipose Tissue Inflammation in Obesity
Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: CD68 Gene Expression by Immunohistochemistry of Adipose TissueInsulin Sensitivity by Intravenous Glucose Tolerance Testing (Change Over Time)
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 18-75 years of age
- Weight stable for previous 6 months (+2. 0kg)
- Sedentary to recreationally active
- Willing to be randomized to treatment or placebo
- Verbal and written informed consent
- Approved for participation by Medical Director (Jose Rivero, M. D.)
Exclusion Criteria:
- Blood pressure outside stated range
- Diabetes or taking diabetes medications
- Total cholesterol >6. 2 mmol/L; triglycerides >4. 5 mmol/L
- Past or current ischemic heart disease, stroke, respiratory disease, endocrine or
metabolic disease, neurological disease, or hematological-oncological disease
- Evidence of renal insufficiency; GFR< 60 ml/min*
- Medications (including but not limited to antihypertensives, statins or other with
anti-inflammatory actions) or antioxidant vitamins or supplements
- Known allergy or hypersensitivity to olmesartan or any of its components
- Pregnant or planning to become pregnant
Locations and Contacts
Additional Information
Starting date: February 2009
Last updated: January 8, 2015
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