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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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The main purposes of this study are to find out if the study drug losartan (Cozaar) or placebo ("sugar pill") has an effect on insulin sensitivity (how your body responds to insulin) and to measure the effect of the study drug losartan or placebo on how the arteries in your arm dilate (enlarge to carry more blood).
We hope to learn if taking losartan changes the amount of certain proteins in the blood that effect blood vessel function.
Losartan is approved by the US FDA to treat high blood pressure. It will take approximately 4 months for you to complete this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Losartan | Active Comparator | Losartan 100 mg 1 tab po QD |
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| Placebo | Placebo Comparator | Placebo 1 tab po QD |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| losartan | Drug | losartan 100 mg tablets 1 tab po QD |
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| Measure | Description | Time Frame |
|---|---|---|
| Insulin Sensitivity Utilizing the Euglycemic Hyperinsulinemic Clamp | Insulin clamp derived insulin sensitivity, as insulin stimulated glucose disposal corrected for steady state insulin level. | baseline, 8 weeks |
| Insulin Sensitivity Utilizing Endothelial Function as Assessed by Pulse Volume Amplitude | Endothelial function assessed as the ratio of pulse volume amplitude after compared with before a reactive hyperemia stimulus, measured by peripheral (fingertip) arterial tonometry. Reported values indicate the percentage change from Baseline in the ratio of pulse volume amplitude after compared to before the reactive hyperemia stimulus. | baseline, 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Urine Albumin/Creatine | Urine was obtained to assess for the presence of microalbuminuria. | baseline, 8 weeks |
| Change in hsCRP (High-sensitivity C-reactive Protein) | hsCRP (high-sensitivity C-reactive protein) is a marker of inflammation |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mark A Creager, MD | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CAVS Clinical Research Center | Little Rock | Arkansas | 72205 | United States | ||
| VA San Diego Health Care System |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21861845 | Result | Perlstein TS, Henry RR, Mather KJ, Rickels MR, Abate NI, Grundy SM, Mai Y, Albu JB, Marks JB, Pool JL, Creager MA. Effect of angiotensin receptor blockade on insulin sensitivity and endothelial function in abdominally obese hypertensive patients with impaired fasting glucose. Clin Sci (Lond). 2012 Feb;122(4):193-202. doi: 10.1042/CS20110284. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Losartan 100 mg 1 Tab po QD | Losartan 100 mg 1 tab po QD |
| FG001 | Placebo 1 Tab po QD | Placebo 1 tab po QD |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Placebo control | Drug | Placebo 1 po QD |
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| baseline, 8 weeks |
| Change in VCAM-1(Vascular Cell-adhesion Molecule-1) | VCAM-1 is an immunoglobulin-like adhesion molecule expressed on activated endothelial cells. | baseline, 8 weeks |
| Change in MCP-1 (Monocyte Chemoattractant Protein-1) | MCP-1 is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages. | baseline, 8 weeks |
| Change in Ox-LDL (Oxidized Low-density Lipoprotein) | ox-LDL measures protein damage due to the oxidative modification of the ApoB subunit on LDL cholesterol. | baseline, 8 weeks |
| Change in F2-isoprostanes | F2-isoprostanes is a marker of oxidative stress. | baseline, 8 weeks |
| Change in E-selectin | E-selectin is expressed on inflamed endothelial cells in response to treatment with inflammatory cytokines. | baseline, 8 weeks |
| San Diego |
| California |
| 92161 |
| United States |
| University of Miami Diabetes Research Institute | Miami | Florida | 33136 | United States |
| Indiana University School of Medicine | Indianapolis | Indiana | 46202 | United States |
| Brigham and Women's Hospital Cardiovascular Division | Boston | Massachusetts | 02115 | United States |
| St. Lukes Roosevelt Hospital | New York | New York | 10025 | United States |
| University of Pennsylvania School of Medicine | Philadelphia | Pennsylvania | 19104 | United States |
| University of Texas SW Medical Center at Dallas | Dallas | Texas | 75390 | United States |
| Hypertension Clinical Pharmacology Baylor Clinic | Houston | Texas | 77030 | United States |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Losartan 100 mg 1 Tab po QD | Losartan 100 mg 1 tab po QD |
| BG001 | Placebo 1 Tab po QD | Placebo 1 tab po QD |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
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| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| 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 Utilizing the Euglycemic Hyperinsulinemic Clamp | Insulin clamp derived insulin sensitivity, as insulin stimulated glucose disposal corrected for steady state insulin level. | analysis was ITT, but limited to those with interpretable data (3 clamp studies were excluded) | Posted | Mean | Standard Deviation | mg/kg/min | baseline, 8 weeks |
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| Primary | Insulin Sensitivity Utilizing Endothelial Function as Assessed by Pulse Volume Amplitude | Endothelial function assessed as the ratio of pulse volume amplitude after compared with before a reactive hyperemia stimulus, measured by peripheral (fingertip) arterial tonometry. Reported values indicate the percentage change from Baseline in the ratio of pulse volume amplitude after compared to before the reactive hyperemia stimulus. | analysis was ITT, but limited to those with interpretable data (3 clamp studies were excluded) | Posted | Mean | Standard Deviation | percentage change | baseline, 8 weeks |
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| Secondary | Change in Urine Albumin/Creatine | Urine was obtained to assess for the presence of microalbuminuria. | 27 participants were randomized to placebo, and 26 participants were randomized to Losartan, but 1 placebo participant and 1 Losartan participant did not complete the study. | Posted | Mean | 95% Confidence Interval | mg/mmol | baseline, 8 weeks |
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| Secondary | Change in hsCRP (High-sensitivity C-reactive Protein) | hsCRP (high-sensitivity C-reactive protein) is a marker of inflammation | 27 participants were randomized to placebo, and 26 participants were randomized to Losartan, but 1 placebo participant and 1 Losartan participant did not complete the study. | Posted | Mean | 95% Confidence Interval | percentage change | baseline, 8 weeks |
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| Secondary | Change in VCAM-1(Vascular Cell-adhesion Molecule-1) | VCAM-1 is an immunoglobulin-like adhesion molecule expressed on activated endothelial cells. | 27 participants were randomized to placebo, and 26 participants were randomized to Losartan, but 1 placebo participant and 1 Losartan participant did not complete the study. | Posted | Mean | 95% Confidence Interval | ng/ml | baseline, 8 weeks |
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| Secondary | Change in MCP-1 (Monocyte Chemoattractant Protein-1) | MCP-1 is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages. | 27 participants were randomized to placebo, and 26 participants were randomized to Losartan, but 1 placebo participant and 1 Losartan participant did not complete the study. | Posted | Mean | 95% Confidence Interval | pg/ml | baseline, 8 weeks |
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| Secondary | Change in Ox-LDL (Oxidized Low-density Lipoprotein) | ox-LDL measures protein damage due to the oxidative modification of the ApoB subunit on LDL cholesterol. | 27 participants were randomized to placebo, and 26 participants were randomized to Losartan, but 1 placebo participant and 1 Losartan participant did not complete the study. | Posted | Mean | 95% Confidence Interval | units/l | baseline, 8 weeks |
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| Secondary | Change in F2-isoprostanes | F2-isoprostanes is a marker of oxidative stress. | 27 participants were randomized to placebo, and 26 participants were randomized to Losartan, but 1 placebo participant and 1 Losartan participant did not complete the study. | Posted | Mean | 95% Confidence Interval | ng/mg of creatinine | baseline, 8 weeks |
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| Secondary | Change in E-selectin | E-selectin is expressed on inflamed endothelial cells in response to treatment with inflammatory cytokines. | 27 participants were randomized to placebo, and 26 participants were randomized to Losartan, but 1 placebo participant and 1 Losartan participant did not complete the study. | Posted | Mean | 95% Confidence Interval | ng/ml | baseline, 8 weeks |
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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 | Losartan | Losartan 100 mg 1 tab po QD | 0 | 26 | 0 | 26 | ||
| EG001 | Placebo | Placebo 1 tab po QD | 0 | 27 | 0 | 27 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mark A. Creager, MD | Brigham and Women's Hospital | 617-732-5267 | mcreager@partners.org |
| ID | Term |
|---|---|
| D009765 | Obesity |
| D006973 | Hypertension |
| D006943 | Hyperglycemia |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| D019808 | Losartan |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013777 | Tetrazoles |
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| >=65 years |
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| Male |
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