Hypertension, Diabetes
Conditions
Brief summary
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.
Detailed description
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).
Interventions
DRUGSalsalate
Salsalate 750 mg
DRUGCarvedilol
Carvedilol 3.125 mg
DRUGPlacebo
One tablet
DRUGIntralipid 20%
24-hour infusion of Intralipid 20% solution at 20 mL/h (96 g/24 h)
Sponsors
American Diabetes Association
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Males or females * Obese subjects (body mass index (BMI) ≥ 30 kg/m\^2) * 18 and 65 years * Blood pressure reading \< 140/80 mm Hg and no prior history of hypertension
Exclusion criteria
* History of diabetes mellitus * History of hypertension * Fasting triglyceride levels \> 250 mg/dL * Liver disease (ALT 2.5x \> upper limit of normal) * Serum creatinine ≥1.5 mg/dL * Smokers, drug or alcohol abuse * Mental condition rendering the subject unable to understand the scope and possible consequences of the study * Female subjects who are pregnant or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Systolic Blood Pressure. | Pre-dose (Baseline), within 4 hours at Baseline visit | 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. |
| Change in Systolic Blood Pressure | Pre-dose (Baseline), within 8 hours at Baseline visit | 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. |
| Change in Flow-mediated Dilation | Pre-dose (Baseline), within 12 hours at Baseline visit | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Expression of Inflammatory Biomarker Interleukin-6 (IL-6) | Baseline, 6 weeks | It is measured by using microsphere-based flow cytometric immunoassay. Change is the difference between 6-week level from baseline level. |
| Change in FFA (Free Fatty Acid) Levels From Baseline to 6 Weeks | Baseline, 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. |
| Change in Diastolic Blood Pressure From Baseline to 6 Weeks | Baseline, 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. |
| Change in Expression of Inflammatory Biomarker C-Reactive Protein (CRP) | Baseline, 6 weeks | It is measured by using microsphere-based flow cytometric immunoassay. Change is the difference between 6-week inflammatory biomarker level from baseline level. |
| Change in Pulse Wave Velocity (PWV) | Baseline, 6 weeks | 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. |
| Change in Oxidative Stress Markers. | Baseline, 6 weeks | 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. |
| Change in Augmentation Index (AIx) | Baseline, 6 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects recruited from July 2009 to January 2011 at Grady Memorial Hospital.
Pre-assignment details
All subjects will receive IV Intralipid (20% solution at 20 ml/hour) prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 11 |
| 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. | 12 |
| 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. | 12 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 4 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Salsalate | Carvedilol | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 34 years STANDARD_DEVIATION 11 | 41 years STANDARD_DEVIATION 11 | 37.5 years STANDARD_DEVIATION 8 | 37.5 years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 2 Participants | 15 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
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
Time frame: Pre-dose (Week 6), within 24 hours at Week 6 visit
Population: 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Flow-mediated Dilation | 0.39 percent change in diameter | Standard Deviation 0.28 |
| Carvedilol | Change in Flow-mediated Dilation | 0.70 percent change in diameter | Standard Deviation 0.52 |
| Placebo | Change in Flow-mediated Dilation | 0.48 percent change in diameter | Standard Deviation 0.29 |
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.
Time frame: Pre-dose (Baseline), within 12 hours at Baseline visit
Population: One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Flow-mediated Dilation | 0.14 percent change in diameter | Standard Deviation 0.27 |
| Carvedilol | Change in Flow-mediated Dilation | 0.24 percent change in diameter | Standard Deviation 0.22 |
| Placebo | Change in Flow-mediated Dilation | 0.26 percent change in diameter | Standard Deviation 0.34 |
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
Time frame: Pre-dose (Baseline), within 24 hours at Baseline visit
Population: One subject on the salsalate arm withdrew from the study was not included in the baseline analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Flow-mediated Dilation | 0.35 percent change in diameter | Standard Deviation 0.29 |
| Carvedilol | Change in Flow-mediated Dilation | 0.53 percent change in diameter | Standard Deviation 0.47 |
| Placebo | Change in Flow-mediated Dilation | 0.47 percent change in diameter | Standard Deviation 0.45 |
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.
Time frame: Pre-dose (Week 6), within 12 hours at Week 6 visit
Population: 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Flow-mediated Dilation | 0.22 percent change in diameter | Standard Deviation 0.27 |
| Carvedilol | Change in Flow-mediated Dilation | 0.42 percent change in diameter | Standard Deviation 0.43 |
| Placebo | Change in Flow-mediated Dilation | 0.20 percent change in diameter | Standard Deviation 0.26 |
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.
Time frame: Pre-dose (Baseline), within 12 hours at Baseline visit
Population: One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Systolic Blood Pressure | 20.55 mmHg | Standard Deviation 10.06 |
| Carvedilol | Change in Systolic Blood Pressure | 1.74 mmHg | Standard Deviation 10.59 |
| Placebo | Change in Systolic Blood Pressure | 5.25 mmHg | Standard Deviation 15.64 |
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.
Time frame: Pre-dose (Baseline), within 20 hours at Baseline visit
Population: One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Systolic Blood Pressure | 13.27 mmHg | Standard Deviation 9.84 |
| Carvedilol | Change in Systolic Blood Pressure | 9.39 mmHg | Standard Deviation 8.36 |
| Placebo | Change in Systolic Blood Pressure | 11.4 mmHg | Standard Deviation 12.7 |
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.
Time frame: Pre-dose (Baseline), within 24 hours at Baseline visit
Population: One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Systolic Blood Pressure | 13.93 mmHg | Standard Deviation 13.9 |
| Carvedilol | Change in Systolic Blood Pressure | 13.21 mmHg | Standard Deviation 11.64 |
| Placebo | Change in Systolic Blood Pressure | 10.27 mmHg | Standard Deviation 9.38 |
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.
Time frame: Pre-dose (Week 6), within 4 hours at Week 6 visit
Population: 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Systolic Blood Pressure | 11.50 mmHg | Standard Deviation 10.54 |
| Carvedilol | Change in Systolic Blood Pressure | 14.32 mmHg | Standard Deviation 8.92 |
| Placebo | Change in Systolic Blood Pressure | 4.26 mmHg | Standard Deviation 13.99 |
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.
Time frame: Pre-dose (Week 6), within 8 hours at Week 6 visit
Population: 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Systolic Blood Pressure | 10.1 mmHg | Standard Deviation 11.62 |
| Carvedilol | Change in Systolic Blood Pressure | 11.62 mmHg | Standard Deviation 16.15 |
| Placebo | Change in Systolic Blood Pressure | 4.14 mmHg | Standard Deviation 10.43 |
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.
Time frame: Pre-dose (Week 6), within 12 hours at Week 6 visit
Population: 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Systolic Blood Pressure | 9.50 mmHg | Standard Deviation 13.46 |
| Carvedilol | Change in Systolic Blood Pressure | 8.14 mmHg | Standard Deviation 15.34 |
| Placebo | Change in Systolic Blood Pressure | 0.38 mmHg | Standard Deviation 14.13 |
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.
Time frame: Pre-dose (Week 6), within 16 hours at Week 6 visit
Population: 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Systolic Blood Pressure | 7.85 mmHg | Standard Deviation 12.6 |
| Carvedilol | Change in Systolic Blood Pressure | 7.55 mmHg | Standard Deviation 8.78 |
| Placebo | Change in Systolic Blood Pressure | -0.04 mmHg | Standard Deviation 6.69 |
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.
Time frame: Pre-dose (Week 6), within 20 hours at Week 6 visit
Population: 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Systolic Blood Pressure | 12.88 mmHg | Standard Deviation 12.84 |
| Carvedilol | Change in Systolic Blood Pressure | 8.84 mmHg | Standard Deviation 12.25 |
| Placebo | Change in Systolic Blood Pressure | 6.6 mmHg | Standard Deviation 9.28 |
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.
Time frame: Pre-dose (Week 6), within 24 hours at Week 6 visit
Population: 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Systolic Blood Pressure | 11.23 mmHg | Standard Deviation 9.56 |
| Carvedilol | Change in Systolic Blood Pressure | 9.92 mmHg | Standard Deviation 7.42 |
| Placebo | Change in Systolic Blood Pressure | 3.04 mmHg | Standard Deviation 9.41 |
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.
Time frame: Pre-dose (Baseline), within 16 hours at Baseline visit
Population: One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Systolic Blood Pressure | 15.78 mmHg | Standard Deviation 13.12 |
| Carvedilol | Change in Systolic Blood Pressure | 8.05 mmHg | Standard Deviation 9.35 |
| Placebo | Change in Systolic Blood Pressure | 3.6 mmHg | Standard Deviation 13.34 |
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.
Time frame: Pre-dose (Baseline), within 8 hours at Baseline visit
Population: One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Systolic Blood Pressure | 13.02 mmHg | Standard Deviation 16.42 |
| Carvedilol | Change in Systolic Blood Pressure | 2.03 mmHg | Standard Deviation 11.27 |
| Placebo | Change in Systolic Blood Pressure | 5.47 mmHg | Standard Deviation 16.81 |
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.
Time frame: Pre-dose (Baseline), within 4 hours at Baseline visit
Population: One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Systolic Blood Pressure. | 15.37 mmHg | Standard Deviation 9.15 |
| Carvedilol | Change in Systolic Blood Pressure. | 10.04 mmHg | Standard Deviation 8.72 |
| Placebo | Change in Systolic Blood Pressure. | 10.25 mmHg | Standard Deviation 12.83 |
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.
Time frame: Baseline, 6 weeks
Population: not assessed (limited funds available)
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.
Time frame: Baseline, 6 weeks
Population: 6 subjects were lost to follow up, 1 withdrew from the study, and data was not collected for 1 additional subject
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Diastolic Blood Pressure From Baseline to 6 Weeks | 1.00 mmHg | Standard Deviation 10.13 |
| Carvedilol | Change in Diastolic Blood Pressure From Baseline to 6 Weeks | -1.50 mmHg | Standard Deviation 6.93 |
| Placebo | Change in Diastolic Blood Pressure From Baseline to 6 Weeks | 2.22 mmHg | Standard Deviation 10.49 |
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.
Time frame: Baseline, 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Expression of Inflammatory Biomarker C-Reactive Protein (CRP) | 2.55 mg/dL | Standard Deviation 7.67 |
| Carvedilol | Change in Expression of Inflammatory Biomarker C-Reactive Protein (CRP) | -7.08 mg/dL | Standard Deviation 17.94 |
| Placebo | Change in Expression of Inflammatory Biomarker C-Reactive Protein (CRP) | -0.20 mg/dL | Standard Deviation 2.82 |
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.
Time frame: Baseline, 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in Expression of Inflammatory Biomarker Interleukin-6 (IL-6) | -0.29 pg/ml | Standard Deviation 0.93 |
| Carvedilol | Change in Expression of Inflammatory Biomarker Interleukin-6 (IL-6) | -1.84 pg/ml | Standard Deviation 5.43 |
| Placebo | Change in Expression of Inflammatory Biomarker Interleukin-6 (IL-6) | -0.36 pg/ml | Standard Deviation 1.24 |
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.
Time frame: Baseline, 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salsalate | Change in FFA (Free Fatty Acid) Levels From Baseline to 6 Weeks | -0.08 mmol/L | Standard Deviation 0.32 |
| Carvedilol | Change in FFA (Free Fatty Acid) Levels From Baseline to 6 Weeks | 0.04 mmol/L | Standard Deviation 0.22 |
| Placebo | Change in FFA (Free Fatty Acid) Levels From Baseline to 6 Weeks | 0.03 mmol/L | Standard Deviation 0.43 |
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.
Time frame: Baseline, 6 weeks
Population: not assessed (limited funds available)
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.
Time frame: Baseline, 6 weeks
Population: not assessed (limited funds available)