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Angiotensin II Blockade and Inflammation in Obesity (ARB)

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ClinicalTrials.gov Identifier: NCT01684748
Recruitment Status : Completed
First Posted : September 13, 2012
Results First Posted : January 12, 2015
Last Update Posted : January 3, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Kevin Davy, Virginia Polytechnic Institute and State University

Tracking Information
First Submitted Date  ICMJE September 6, 2012
First Posted Date  ICMJE September 13, 2012
Results First Submitted Date  ICMJE May 29, 2014
Results First Posted Date  ICMJE January 12, 2015
Last Update Posted Date January 3, 2018
Study Start Date  ICMJE February 2009
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 1, 2017)
Insulin Sensitivity by Intravenous Glucose Tolerance Testing (Change Over Time) [ Time Frame: Baseline testing to post-testing after 8-week intervention ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 10, 2012)
CD68 Gene Expression by Immunohistochemistry of Adipose Tissue [ Time Frame: 8 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2012)
Insulin sensitivity by intravenous glucose tolerance testing [ Time Frame: 8 weeks ]
Current Other Pre-specified Outcome Measures
 (submitted: November 1, 2017)
Collagen Gene Expression in Skeletal Muscle (Change Over Time) [ Time Frame: Baseline testing to post-testing after 8-week intervention ]
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.
Original Other Pre-specified Outcome Measures
 (submitted: September 10, 2012)
Proinflammatory and Collagen Gene Expression in Skeletal Muscle [ Time Frame: 8 weeks ]
 
Descriptive Information
Brief Title  ICMJE Angiotensin II Blockade and Inflammation in Obesity
Official Title  ICMJE Angiotensin II Blockade and Adipose Tissue Inflammation in Obesity
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Overweight
  • Obese
  • Prehypertension
  • Hypertension
Intervention  ICMJE Drug: Olmesartan medoxomil
Crossover intervention comparing antihypertensive medication to no drug intervention.
Other Name: Benicar
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Olmesartan medoxomil
  • 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.
    Intervention: Drug: Olmesartan medoxomil
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 10, 2012)
20
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2011
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01684748
Other Study ID Numbers  ICMJE arbfat
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kevin Davy, Virginia Polytechnic Institute and State University
Study Sponsor  ICMJE Virginia Polytechnic Institute and State University
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Kevin P. Davy, Ph.D. Virginia Polytechnic Institute and State University
PRS Account Virginia Polytechnic Institute and State University
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP