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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Olmesartan medoxomil | Drug | Crossover intervention comparing antihypertensive medication to no drug intervention. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline testing to post-testing after 8-week intervention |
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| Measure | Description | Time Frame |
|---|---|---|
| Collagen Gene Expression in Skeletal Muscle (Change Over Time) | 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kevin P. Davy, Ph.D. | Virginia Polytechnic Institute and State University | Principal Investigator |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Olmesartan medoxomil |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention - 8 Weeks |
| |||||||||||||
| Second Intervention - 8 Weeks |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Olmesartan medoxomil |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Results of insulin sensitivity by intravenous glucose tolerance (IVGTT) testing are reported per intervention (Olmesartan Medoxomil and No drug). Only 10 of the 16 study participants who participated in all or some of the study measurements opted to complete or had sufficient data to analyze for each pre- and post-intervention (4 total) IVGTT. | Posted | Mean | Standard Deviation | mu/L/min | Baseline testing to post-testing after 8-week intervention |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Olmesartan Medoxomil | Subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks during the 8-week intervention. 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. Olmesartan medoxomil |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Elaina Marinik, Ph.D. | Virginia Polytechnic Institute & State University | 5402318299 | emarinik@vt.edu |
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| ID | Term |
|---|---|
| D050177 | Overweight |
| D009765 | Obesity |
| D058246 | Prehypertension |
| D006973 | Hypertension |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
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| ID | Term |
|---|---|
| D000068557 | Olmesartan Medoxomil |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| Baseline testing to post-testing after 8-week intervention |
| NOT COMPLETED |
|
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Age, Categorical | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body weight | Mean | Standard Deviation | kg |
|
| Body mass index | Mean | Standard Deviation | kg/m2 |
|
| Body fat | Mean | Standard Deviation | Percentage of fat |
|
| Total fat mass | Mean | Standard Deviation | kg |
|
| Systolic blood pressure | Mean | Standard Deviation | mmHg |
|
| Diastolic blood pressure | Mean | Standard Deviation | mmHg |
|
| Triglycerides | Mean | Standard Deviation | mg/dL |
|
| Total cholesterol | Mean | Standard Deviation | mg/dL |
|
| HDL cholesterol | Mean | Standard Deviation | mg/dL |
|
| LDL cholesterol | Mean | Standard Deviation | mg/dL |
|
| Glucose | Mean | Standard Deviation | mg/dL |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Olmesartan Medoxomil | Subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks during the 8-week intervention. 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. Olmesartan medoxomil |
| OG001 | No Drug Intervention | The no-drug intervention (i.e., no placebo is provided) is an 8-week no intervention comparison. |
|
|
| Other Pre-specified | Collagen Gene Expression in Skeletal Muscle (Change Over Time) | 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. | Results are reported for the Olmesartan Medoxomil intervention only; there was insufficient RNA yield for the majority of participants during the no drug treatment. Only 7 of the 16 study participants who participated in the study measurements had sufficient data to analyze the pre- and post-intervention skeletal muscle biopsy tissues. | Posted | Mean | Standard Error | Arbitrary unit (AU) | Baseline testing to post-testing after 8-week intervention |
|
|
|
| 0 |
| 16 |
| 0 |
| 16 |
| EG001 | No Drug Intervention | The no-drug intervention (i.e., no placebo is provided) is an 8-week no intervention comparison. | 0 | 16 | 0 | 16 |
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| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D013777 |
| Tetrazoles |