Angiotensin II Blockade and Inflammation in Obesity (ARB)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Kevin Davy, Virginia Polytechnic Institute and State University
ClinicalTrials.gov Identifier:
NCT01684748
First received: September 6, 2012
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

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 medoxidil, 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.


Condition Intervention Phase
Overweight
Obese
Prehypertension
Hypertension
Drug: Olmesartan medoxomil
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Angiotensin II Blockade and Adipose Tissue Inflammation in Obesity

Resource links provided by NLM:


Further study details as provided by Virginia Polytechnic Institute and State University:

Primary Outcome Measures:
  • CD68 gene expression by immunohistochemistry of adipose tissue [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Insulin sensitivity by intravenous glucose tolerance testing [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Proinflammatory and collagen gene expression in skeletal muscle [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: February 2009
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: olmesartan medoxomil
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. The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks. Subjects will continue taking the drug during the 2-week follow-up period. Subjects will take no drug during the control period (ie., no placebo is provided).
Drug: Olmesartan medoxomil
Other Name: Benicar
No Intervention: No drug intervention
The no drug intervention is a no intervention comparison

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01684748

Sponsors and Collaborators
Virginia Polytechnic Institute and State University
Investigators
Principal Investigator: Kevin P. Davy, Ph.D. Virginia Polytechnic Institute and State University
  More Information

No publications provided

Responsible Party: Kevin Davy, Professor, Virginia Polytechnic Institute and State University
ClinicalTrials.gov Identifier: NCT01684748     History of Changes
Other Study ID Numbers: arbfat
Study First Received: September 6, 2012
Last Updated: December 16, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Virginia Polytechnic Institute and State University:
angiotensin II
obesity
diabetes

Additional relevant MeSH terms:
Hypertension
Obesity
Inflammation
Overweight
Prehypertension
Vascular Diseases
Cardiovascular Diseases
Overnutrition
Nutrition Disorders
Body Weight
Signs and Symptoms
Pathologic Processes
Olmesartan
Olmesartan medoxomil
Angiotensin II
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on September 18, 2014