Angiotensin II Blockade and Inflammation in Obesity

NCT ID: NCT01684748

Last Updated: 2018-01-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2011-08-31

Brief 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.

Conditions

Overweight; Obese; Prehypertension; Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Olmesartan Medoxomil first, then No Drug

During the First Intervention (8 weeks), subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks. Subjects receive additional daily doses of 40 mg olmesartan for the remainder of the study period (6 weeks). The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks. In addition, subjects will continue taking the drug during the 2-week follow-up testing period. Subjects will then proceed to the Washout period (2 weeks). During the Second Intervention (8 weeks), no drug will be administered to the subjects.

Group Type: EXPERIMENTAL

Olmesartan medoxomil

Intervention Type: DRUG

Crossover intervention comparing antihypertensive medication to no drug intervention.

No Drug first, then Olmesartan Medoxomil

During the First Intervention (8 weeks), no drug will be administered to the subjects. Subjects will then proceed to the Washout period (2 weeks). During the Second Intervention (8 weeks), subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks. Subjects then receive daily doses of 40 mg olmesartan for the remainder of the study period (6 weeks). The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks. In addition, subjects will continue taking the drug during the 2-week follow-up testing period.

Group Type: EXPERIMENTAL

Olmesartan medoxomil

Intervention Type: DRUG

Crossover intervention comparing antihypertensive medication to no drug intervention.

Interventions

Olmesartan medoxomil

Crossover intervention comparing antihypertensive medication to no drug intervention.

Intervention Type: DRUG

Other Intervention Names

Benicar

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Virginia Polytechnic Institute and State University

OTHER

Sponsor Role: lead

Responsible Party

Kevin Davy

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kevin P. Davy, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Virginia Polytechnic Institute and State University

Other Identifiers

arbfat

Identifier Type: -

Identifier Source: org_study_id