Angiotensin II Blockade and Inflammation in Obesity

Hypertension Clinical Trial

— ARB  

Official title:

Angiotensin II Blockade and Adipose Tissue Inflammation in Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01684748
• Other study ID #: arbfat
• Status: Completed
• Phase: Phase 4
• First received: September 6, 2012
• Last updated: December 6, 2017
• Start date: February 2009
• Est. completion date: August 2011

Study information

• Verified date: December 2017
• Source: Virginia Polytechnic Institute and State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Inflammation
• Obese
• Obesity
• Overweight
• Prehypertension

Intervention

Drug:
• Olmesartan medoxomil
Crossover intervention comparing antihypertensive medication to no drug intervention.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Polytechnic Institute and State University	National Heart, Lung, and Blood Institute (NHLBI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Collagen Gene Expression in Skeletal Muscle (Change Over Time)	RNA extraction and quantification were determined using an RNeasy Mini Fibrous Kit and DNase I treatment (Qiagen, Valencia, CA, USA) in accordance to the manufacturer's directions for mRNA extraction. Quantitative real-time polymerase chain reaction (qRT-PCR) measured the expression of collagen III using an ABI PRISM 7900 Sequence Detection System instrument and TaqMan Universal PCR Master Mix according to the manufacturer's instructions (Applied Biosystems, Foster City, CA, USA). Relative gene expression levels were determined using the number of cycles necessary to reach threshold and results were normalized to cyclophilin B RNA levels.	Baseline testing to post-testing after 8-week intervention
Primary	Insulin Sensitivity by Intravenous Glucose Tolerance Testing (Change Over Time)	Data collected from the intravenous glucose tolerance tests included blood concentrations of glucose and insulin. Glucose was measured immediately on a YSI glucose analyzer and insulin was measured via ELISA colormetric kits once all study samples were collected. To analyze changes in insulin sensitivity, the MINMOD software was used. The MINMOD software uses Bergman's minimal model to determine insulin sensitivity during an intravenous glucose tolerance test. Both glucose and insulin values were inserted at each timepoint collected (33 in total over the 3-hour protocol) and the software was run to generate the insulin sensitivity value at baseline and post-test. This information was then used to calculate the change of insulin sensitivity from baseline to post-testing after each 8-week intervention.	Baseline testing to post-testing after 8-week intervention