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: January 8, 2015
Last verified: January 2015
  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 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.


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 ]
  • Insulin Sensitivity by Intravenous Glucose Tolerance Testing (Change Over Time) [ Time Frame: Baseline testing to post-testing after 8-week intervention ] [ Designated as safety issue: No ]
    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.


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 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.
Drug: Olmesartan medoxomil
Crossover intervention comparing antihypertensive medication to no drug intervention.
Other Name: Benicar
Experimental: 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.
Drug: Olmesartan medoxomil
Crossover intervention comparing antihypertensive medication to no drug intervention.
Other Name: Benicar

  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
Results First Received: May 29, 2014
Last Updated: January 8, 2015
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Prehypertension
Cardiovascular Diseases
Vascular Diseases
Angiotensin II
Olmesartan
Olmesartan medoxomil
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Antihypertensive Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on April 16, 2015