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| Name | Class |
|---|---|
| American Diabetes Association | OTHER |
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The purpose of this study is to see if salsalate, an Nuclear factor-kappaB (NF-κB) mediated inflammation inhibitor, or carvedilol, an α- and β-blocker, will protect against free fatty acid induced hypertension, insulin resistance, endothelial dysfunction, inflammation and oxidative stress, and autonomic dysfunction in obese normotensive subjects.
During postprandial lipemia, dietary triglycerides transported by intestinal chylomicrons are hydrolyzed by lipoprotein lipase lining the vascular bed, with subsequent release of FFA for transport across the endothelium. Whether the intermittent flux of FFA has the same impact as the i.v. lipid infusion will be examined. Decreased endothelial function has been reported after a single or long-term dietary high fat load in normal subjects; however, others have found no effects on brachial artery vasoreactivity. Our preliminary studies indicate that high oral fat loads (60 g) resulted in higher FFA levels and BP changes, and reduced FMD compared to low fat load (25 g).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Salsalate | Experimental | Obese, normotensive, healthy subjects will receive an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject has no side effects, the dose will be increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects will then receive another 24-hour IV administration of Intralipid 20% at the 6-week point. |
|
| Carvedilol | Experimental | Obese, normotensive, healthy subjects will receive an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject has no side effects, the dose will be increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects will then receive another 24-hour IV administration of Intralipid 20% at the 6-week point. |
|
| Placebo | Placebo Comparator | Obese, normotensive, healthy subjects will receive an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose will be increased to two placebo tablets twice daily for the remaining four weeks. The subjects will then receive another 24-hour IV administration of Intralipid 20% at the 6-week point. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Salsalate | Drug | Salsalate 750 mg |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Systolic Blood Pressure. | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 4 hours during Intralipid infusion. | Pre-dose (Baseline), within 4 hours at Baseline visit |
| Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. from Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 8 hours during Intralipid. | Pre-dose (Baseline), within 8 hours at Baseline visit |
| Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 12 hours during Intralipid infusion. | Pre-dose (Baseline), within 12 hours at Baseline visit |
| Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 16 hours during Intralipid infusion. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Diastolic Blood Pressure From Baseline to 6 Weeks | Diastolic blood pressure is the amount of pressure in the arteries when the heart is at rest between beats. Current guidelines identify normal diastolic blood pressure as lower than 80 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 8 hour infusion with subjects in supine position. Change is the difference between 6-week diastolic blood pressure from baseline diastolic blood pressure. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Guillermo Umpierrez, MD | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Grady Memorial Hospital | Atlanta | Georgia | 30303 | United States |
All subjects will receive IV Intralipid (20% solution at 20 ml/hour) prior to randomization.
Subjects recruited from July 2009 to January 2011 at Grady Memorial Hospital.
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| ID | Title | Description |
|---|---|---|
| FG000 | Salsalate | Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point. |
| FG001 | Carvedilol | Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point. |
| FG002 | Placebo | Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All but one of the subjects that completed the study were included in the baseline analysis. No data was recorded for one subject who withdrew from the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Salsalate | Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point. |
| 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 | Change in Systolic Blood Pressure. | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 4 hours during Intralipid infusion. | One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population. | Posted | Mean | Standard Deviation | mmHg | Pre-dose (Baseline), within 4 hours at Baseline visit |
|
6 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 | Salsalate | Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Guillermo Umpierrez | Emory University | 404-778-1665 | geumpie@emory.edu |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| C014182 | salicylsalicylic acid |
| D000894 | Anti-Inflammatory Agents, Non-Steroidal |
| D000077261 | Carvedilol |
| ID | Term |
|---|---|
| D018712 | Analgesics, Non-Narcotic |
| D000700 | Analgesics |
| D018689 | Sensory System Agents |
| D018373 | Peripheral Nervous System Agents |
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| Carvedilol | Drug | Carvedilol 3.125 mg |
|
|
| Placebo | Drug | One tablet |
|
| Intralipid 20% | Drug | 24-hour infusion of Intralipid 20% solution at 20 mL/h (96 g/24 h) |
|
|
| Pre-dose (Baseline), within 16 hours at Baseline visit |
| Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 20 hours during Intralipid infusion. | Pre-dose (Baseline), within 20 hours at Baseline visit |
| Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 24 hours during Intralipid infusion. | Pre-dose (Baseline), within 24 hours at Baseline visit |
| Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 4 hours during Intralipid infusion. | Pre-dose (Week 6), within 4 hours at Week 6 visit |
| Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure from at Week 6 from pre-dosing with Intralipid to 8 hours during Intralipid infusion. | Pre-dose (Week 6), within 8 hours at Week 6 visit |
| Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 12 hours during Intralipid infusion. | Pre-dose (Week 6), within 12 hours at Week 6 visit |
| Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 16 hours during Intralipid infusion. | Pre-dose (Week 6), within 16 hours at Week 6 visit |
| Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 20 hours during Intralipid infusion. | Pre-dose (Week 6), within 20 hours at Week 6 visit |
| Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 24 hours during Intralipid infusion. | Pre-dose (Week 6), within 24 hours at Week 6 visit |
| Change in Flow-mediated Dilation | The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the baseline visit from pre-dosing with Intralipid to 12 hours during Intralipid infusion. | Pre-dose (Baseline), within 12 hours at Baseline visit |
| Change in Flow-mediated Dilation | The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the baseline visit from pre-dosing with Intralipid to 24 hours during Intralipid infusion | Pre-dose (Baseline), within 24 hours at Baseline visit |
| Change in Flow-mediated Dilation | The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the Week 6 visit from pre-dosing with Intralipid to 12 hours during Intralipid infusion. | Pre-dose (Week 6), within 12 hours at Week 6 visit |
| Change in Flow-mediated Dilation | The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the Week 6 visit from pre-dosing with Intralipid to 24 hours during Intralipid infusion | Pre-dose (Week 6), within 24 hours at Week 6 visit |
| Baseline, 6 weeks |
| Change in Oxidative Stress Markers. | Oxidative stress was measured by using liquid chromatography to collect plasma glutathione and glutathione disulfide. Change is the difference between 6-week plasma glutathione and glutathione disulfide from baseline plasma glutathione and glutathione disulfide. | Baseline, 6 weeks |
| Change in Augmentation Index (AIx) | AIx is a surrogate measure of peripheral arterial resistance and is measured by analysis of the pulse wave at the radial artery. The AIx is calculated as the ratio of the pulse pressure at the second systolic peak to that at the first systolic peak. Change is the difference between 6-week AIx from baseline AIx. | Baseline, 6 weeks |
| Change in Expression of Inflammatory Biomarker Interleukin-6 (IL-6) | It is measured by using microsphere-based flow cytometric immunoassay. Change is the difference between 6-week level from baseline level. | Baseline, 6 weeks |
| Change in FFA (Free Fatty Acid) Levels From Baseline to 6 Weeks | Blood samples were collected for measurement of free fatty acids at baseline and 6 weeks after the Intralipid 20% infusion. FFA levels were determined by colorimetric method. Current guidelines identify normal range of FFA level as less than 0.72 mmol/L. Elevated plasma levels of FFA indicate a greater rate of insulin resistance. Change is the difference between 6-week FFA levels from baseline FFA levels. | Baseline, 6 weeks |
| Change in Pulse Wave Velocity (PWV) | PWV was measured between the carotid and femoral arteries using the SphygmoCor device. Pressure waveforms at the carotid and femoral arteries were acquired using EKG gating. Velocity (distance per time in milliseconds) was calculated using the foot-to-foot method and the distance between the sites was measured manually. | Baseline, 6 weeks |
| Change in Expression of Inflammatory Biomarker C-Reactive Protein (CRP) | It is measured by using microsphere-based flow cytometric immunoassay. Change is the difference between 6-week inflammatory biomarker level from baseline level. | Baseline, 6 weeks |
| BG001 | Carvedilol | Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point. |
| BG002 | Placebo | Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Carvedilol | Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point. |
| OG002 | Placebo | Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point. |
|
|
| Primary | Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. from Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 8 hours during Intralipid. | One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population. | Posted | Mean | Standard Deviation | mmHg | Pre-dose (Baseline), within 8 hours at Baseline visit |
|
|
|
| Primary | Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 12 hours during Intralipid infusion. | One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population. | Posted | Mean | Standard Deviation | mmHg | Pre-dose (Baseline), within 12 hours at Baseline visit |
|
|
|
| Primary | Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 16 hours during Intralipid infusion. | One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population. | Posted | Mean | Standard Deviation | mmHg | Pre-dose (Baseline), within 16 hours at Baseline visit |
|
|
|
| Primary | Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 20 hours during Intralipid infusion. | One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population. | Posted | Mean | Standard Deviation | mmHg | Pre-dose (Baseline), within 20 hours at Baseline visit |
|
|
|
| Primary | Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 24 hours during Intralipid infusion. | One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population. | Posted | Mean | Standard Deviation | mmHg | Pre-dose (Baseline), within 24 hours at Baseline visit |
|
|
|
| Primary | Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 4 hours during Intralipid infusion. | 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject. | Posted | Mean | Standard Deviation | mmHg | Pre-dose (Week 6), within 4 hours at Week 6 visit |
|
|
|
| Primary | Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure from at Week 6 from pre-dosing with Intralipid to 8 hours during Intralipid infusion. | 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject. | Posted | Mean | Standard Deviation | mmHg | Pre-dose (Week 6), within 8 hours at Week 6 visit |
|
|
|
| Primary | Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 12 hours during Intralipid infusion. | 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject. | Posted | Mean | Standard Deviation | mmHg | Pre-dose (Week 6), within 12 hours at Week 6 visit |
|
|
|
| Primary | Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 16 hours during Intralipid infusion. | 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject. | Posted | Mean | Standard Deviation | mmHg | Pre-dose (Week 6), within 16 hours at Week 6 visit |
|
|
|
| Primary | Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 20 hours during Intralipid infusion. | 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject. | Posted | Mean | Standard Deviation | mmHg | Pre-dose (Week 6), within 20 hours at Week 6 visit |
|
|
|
| Primary | Change in Systolic Blood Pressure | Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 24 hours during Intralipid infusion. | 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject. | Posted | Mean | Standard Deviation | mmHg | Pre-dose (Week 6), within 24 hours at Week 6 visit |
|
|
|
| Primary | Change in Flow-mediated Dilation | The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the baseline visit from pre-dosing with Intralipid to 12 hours during Intralipid infusion. | One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population. | Posted | Mean | Standard Deviation | percent change in diameter | Pre-dose (Baseline), within 12 hours at Baseline visit |
|
|
|
| Primary | Change in Flow-mediated Dilation | The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the baseline visit from pre-dosing with Intralipid to 24 hours during Intralipid infusion | One subject on the salsalate arm withdrew from the study was not included in the baseline analysis population. | Posted | Mean | Standard Deviation | percent change in diameter | Pre-dose (Baseline), within 24 hours at Baseline visit |
|
|
|
| Primary | Change in Flow-mediated Dilation | The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the Week 6 visit from pre-dosing with Intralipid to 12 hours during Intralipid infusion. | 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject. | Posted | Mean | Standard Deviation | percent change in diameter | Pre-dose (Week 6), within 12 hours at Week 6 visit |
|
|
|
| Primary | Change in Flow-mediated Dilation | The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the Week 6 visit from pre-dosing with Intralipid to 24 hours during Intralipid infusion | 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject. | Posted | Mean | Standard Deviation | percent change in diameter | Pre-dose (Week 6), within 24 hours at Week 6 visit |
|
|
|
| Secondary | Change in Diastolic Blood Pressure From Baseline to 6 Weeks | Diastolic blood pressure is the amount of pressure in the arteries when the heart is at rest between beats. Current guidelines identify normal diastolic blood pressure as lower than 80 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 8 hour infusion with subjects in supine position. Change is the difference between 6-week diastolic blood pressure from baseline diastolic blood pressure. | 6 subjects were lost to follow up, 1 withdrew from the study, and data was not collected for 1 additional subject | Posted | Mean | Standard Deviation | mmHg | Baseline, 6 weeks |
|
|
|
| Secondary | Change in Oxidative Stress Markers. | Oxidative stress was measured by using liquid chromatography to collect plasma glutathione and glutathione disulfide. Change is the difference between 6-week plasma glutathione and glutathione disulfide from baseline plasma glutathione and glutathione disulfide. | not assessed (limited funds available) | Posted | Baseline, 6 weeks |
|
|
| Secondary | Change in Augmentation Index (AIx) | AIx is a surrogate measure of peripheral arterial resistance and is measured by analysis of the pulse wave at the radial artery. The AIx is calculated as the ratio of the pulse pressure at the second systolic peak to that at the first systolic peak. Change is the difference between 6-week AIx from baseline AIx. | not assessed (limited funds available) | Posted | Baseline, 6 weeks |
|
|
| Secondary | Change in Expression of Inflammatory Biomarker Interleukin-6 (IL-6) | It is measured by using microsphere-based flow cytometric immunoassay. Change is the difference between 6-week level from baseline level. | Posted | Mean | Standard Deviation | pg/ml | Baseline, 6 weeks |
|
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| Secondary | Change in FFA (Free Fatty Acid) Levels From Baseline to 6 Weeks | Blood samples were collected for measurement of free fatty acids at baseline and 6 weeks after the Intralipid 20% infusion. FFA levels were determined by colorimetric method. Current guidelines identify normal range of FFA level as less than 0.72 mmol/L. Elevated plasma levels of FFA indicate a greater rate of insulin resistance. Change is the difference between 6-week FFA levels from baseline FFA levels. | Posted | Mean | Standard Deviation | mmol/L | Baseline, 6 weeks |
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| Secondary | Change in Pulse Wave Velocity (PWV) | PWV was measured between the carotid and femoral arteries using the SphygmoCor device. Pressure waveforms at the carotid and femoral arteries were acquired using EKG gating. Velocity (distance per time in milliseconds) was calculated using the foot-to-foot method and the distance between the sites was measured manually. | not assessed (limited funds available) | Posted | Baseline, 6 weeks |
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| Secondary | Change in Expression of Inflammatory Biomarker C-Reactive Protein (CRP) | It is measured by using microsphere-based flow cytometric immunoassay. Change is the difference between 6-week inflammatory biomarker level from baseline level. | Posted | Mean | Standard Deviation | mg/dL | Baseline, 6 weeks |
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| 0 |
| 12 |
| 0 |
| 12 |
| EG001 | Carvedilol | Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point. | 0 | 12 | 0 | 12 |
| EG002 | Placebo | Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point. | 0 | 12 | 0 | 12 |
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| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000893 | Anti-Inflammatory Agents |
| D045506 | Therapeutic Uses |
| D018501 | Antirheumatic Agents |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D002227 | Carbazoles |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D006575 | Heterocyclic Compounds, 3-Ring |