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Completed

NCT Number: NCT02406586

Free Fatty Acids-Induced Hypertension in Obese Subjects (Aim #2)

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.

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Key information

Conditions

Hypertension Cardiovascular Diseases Diabetes Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases Vascular Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

About this study

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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Salsalate

Drug

Salsalate 750 mg

Other names: Disalcid, NSAID

Carvedilol

Drug

Carvedilol 3.125 mg

Other names: Coreg

Placebo

Drug

One tablet

Intralipid 20%

Drug

24-hour infusion of Intralipid 20% solution at 20 mL/h (96 g/24 h)

Other names: 20% I.V. Fat Emulsion

Primary outcomes

  1. Change in Systolic Blood Pressure.

    Time frame: 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.

  2. Change in Systolic Blood Pressure

    Time frame: 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.

  3. Change in Systolic Blood Pressure

    Time frame: Pre-dose (Baseline), within 12 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 12 hours during Intralipid infusion.

  4. Change in Systolic Blood Pressure

    Time frame: Pre-dose (Baseline), within 16 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 16 hours during Intralipid infusion.

  5. Change in Systolic Blood Pressure

    Time frame: Pre-dose (Baseline), within 20 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 20 hours during Intralipid infusion.

  6. Change in Systolic Blood Pressure

    Time frame: Pre-dose (Baseline), within 24 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 24 hours during Intralipid infusion.

  7. Change in Systolic Blood Pressure

    Time frame: Pre-dose (Week 6), within 4 hours at Week 6 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 Week 6 from pre-dosing with Intralipid to 4 hours during Intralipid infusion.

  8. Change in Systolic Blood Pressure

    Time frame: Pre-dose (Week 6), within 8 hours at Week 6 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 from at Week 6 from pre-dosing with Intralipid to 8 hours during Intralipid infusion.

  9. Change in Systolic Blood Pressure

    Time frame: Pre-dose (Week 6), within 12 hours at Week 6 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 Week 6 from pre-dosing with Intralipid to 12 hours during Intralipid infusion.

  10. Change in Systolic Blood Pressure

    Time frame: Pre-dose (Week 6), within 16 hours at Week 6 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 Week 6 from pre-dosing with Intralipid to 16 hours during Intralipid infusion.

  11. Change in Systolic Blood Pressure

    Time frame: Pre-dose (Week 6), within 20 hours at Week 6 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 Week 6 from pre-dosing with Intralipid to 20 hours during Intralipid infusion.

  12. Change in Systolic Blood Pressure

    Time frame: Pre-dose (Week 6), within 24 hours at Week 6 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 Week 6 from pre-dosing with Intralipid to 24 hours during Intralipid infusion.

  13. Change in Flow-mediated Dilation

    Time frame: 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.

  14. Change in Flow-mediated Dilation

    Time frame: Pre-dose (Baseline), within 24 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 24 hours during Intralipid infusion

  15. Change in Flow-mediated Dilation

    Time frame: Pre-dose (Week 6), within 12 hours at Week 6 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 Week 6 visit from pre-dosing with Intralipid to 12 hours during Intralipid infusion.

  16. Change in Flow-mediated Dilation

    Time frame: Pre-dose (Week 6), within 24 hours at Week 6 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 Week 6 visit from pre-dosing with Intralipid to 24 hours during Intralipid infusion

Secondary outcomes

  1. Change in Diastolic Blood Pressure From Baseline to 6 Weeks

    Time frame: 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.

  2. Change in Oxidative Stress Markers.

    Time frame: 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.

  3. Change in Augmentation Index (AIx)

    Time frame: 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.

  4. Change in Expression of Inflammatory Biomarker Interleukin-6 (IL-6)

    Time frame: Baseline, 6 weeks

    It is measured by using microsphere-based flow cytometric immunoassay. Change is the difference between 6-week level from baseline level.

  5. Change in FFA (Free Fatty Acid) Levels From Baseline to 6 Weeks

    Time frame: 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.

  6. Change in Pulse Wave Velocity (PWV)

    Time frame: 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.

  7. Change in Expression of Inflammatory Biomarker C-Reactive Protein (CRP)

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Emory University

Other

Collaborators

  • American Diabetes Association

Registry information

Official study title

Free Fatty Acids-Induced Hypertension, Endothelial Dysfunction, Inflammation, Insulin Resistance, and Autonomic Dysfunction in Lean and Obese Subjects (Aim #2)

Acronym: FFAADA

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Apr 2, 2015
Registry last updated
Jan 8, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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