OverweightPhase 4ARBNCT01684748
Angiotensin II Blockade and Inflammation in Obesity
A Phase 4 study testing Olmesartan medoxomil in people with Overweight and Obese, run by Virginia Polytechnic Institute and State University.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Overweight, Obese, Prehypertension
- What is being tested?
- Olmesartan medoxomil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- Feb 2009to Aug 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.)
Who cannot join
- 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
About this study
Official title: Angiotensin II Blockade and Adipose Tissue Inflammation in Obesity
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
- Being tested
- Olmesartan medoxomil
- Keywords
- angiotensin II, obesity, diabetes
- Medical subject headings
- Overweight, Obesity, Prehypertension, Hypertension, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Olmesartan medoxomilDrug
Also called Benicar
Crossover intervention comparing antihypertensive medication to no drug intervention.
| Study group | Role | What they receive |
|---|---|---|
| Olmesartan Medoxomil first, then No Drug | Experimental | 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. Receives: Drug: Olmesartan medoxomil |
| No Drug first, then Olmesartan Medoxomil | Experimental | 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. Receives: Drug: Olmesartan medoxomil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline testing to post-testing after 8-week intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2012 (estimated)
- Study startFeb 2009
- Primary completionAug 2011
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for OverweightStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Polytechnic Institute and State University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Kevin Davy, Virginia Polytechnic Institute and State University
- Investigators
- Kevin P. Davy, Ph.D., Principal investigator, Virginia Polytechnic Institute and State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01684748
- Sponsor's protocol ID
- arbfat
- Acronym
- ARB
- Status last verified
- Dec 2017
- First submitted
- 6 Sep 2012
- Last updated
- 3 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Angiotensin II Blockade and Adipose Tissue Inflammation in Obesity
- ClinicalTrials.gov ID
- NCT01684748
- Acronym / sponsor ID
- ARB / arbfat
- Conditions
- Overweight, Obese, Prehypertension, Hypertension
- Keywords
- angiotensin II, obesity, diabetes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Virginia Polytechnic Institute and State UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Feb 2009
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 13 Sep 2012 (estimated)
- Results
- Posted 12 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Olmesartan Medoxomil first, then No Drug | Experimental | Drug: Olmesartan medoxomilDuring 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. |
| No Drug first, then Olmesartan Medoxomil | Experimental | Drug: Olmesartan medoxomilDuring 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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*
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Olmesartan medoxomilAlso: BenicarCrossover intervention comparing antihypertensive medication to no drug intervention. | Drug | No Drug first, then Olmesartan Medoxomil, Olmesartan Medoxomil first, then No Drug |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin P. Davy, Ph.D. principal investigator
Virginia Polytechnic Institute and State University
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Olmesartan medoxomil in people with Overweight and Obese, run by Virginia Polytechnic Institute and State University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin Sensitivity by Intravenous Glucose Tolerance Testing (Change Over Time) (time frame: Baseline testing to post-testing after 8-week intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2018.