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Sponsors and Collaborators: |
Emory University American Heart Association |
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Information provided by: | Emory University |
ClinicalTrials.gov Identifier: | NCT00589888 |
Insulin resistance has been implicated as the central mechanism in the development of several cardiovascular risk factors including hypertension, diabetes, lipid disorders, and coagulation disorders. Recent evidence suggests that increased levels of a circulation fat (free fatty acids or FFAs) are a leading candidate causing insulin resistance. Our preliminary studies in indicate that, in addition to insulin resistance, the infusion of Intralipid and heparin to increase FFAs resulted in a significant rise in systolic and diastolic blood pressure, impaired endothelial (vascular) function, and increased inflammatory markers in obese African Americans with and without diabetes. The effects of FFA on insulin action are well established; however, the blood pressure and vascular effects of FFAs infusion in obese subjects have not been fully investigated. We hypothesize that observed changes in blood pressure are the result of acute endothelial dysfunction, and/or increased activation of the autonomic nervous system. No previous studies have attempted to determine a dose response effect of increasing FFA on blood pressure. In addition, it is not know if increased FFAs by repeated oral fat load results in similar blood pressure than intravenous lipid infusion. Accordingly, we propose: 1) a systematic evaluation of the effects of increasing FFA levels on blood pressure and endothelial (vascular) function, and 2) determine the effects of comparable increases in FFA concentration via intravenous infusion of Intralipid or by repeated oral fat load on blood pressure, insulin resistance and endothelial dysfunction in obese subjects.
A group of 10 obese normotensive subjects will be admitted to the Grady Clinical Research Center or to the Outpatient Research Unit in the Grady Diabetes Clinic on five occasions. In four of these admissions, research subjects will receive an 8-hour intravenous infusion, in random order, of increasing Intralipid concentration (10 ml, 20 ml, 40 ml per hour) or normal saline (40 ml per hour). During the final admission, research subjects will receive an oral liquid fat diet every 2 hours for 8-hours. The effect of increased FFAs on blood pressure and endothelial (vascular) function via intravenous infusion and via oral fat load therapy will be assessed.
Condition | Intervention |
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Endothelial Dysfunction Hypertension |
Drug: Intralipid 20% continuous IV infusion at 10cc/hour for 8 hours Drug: Intralipid 20% Drug: 0.9% Normal Saline Dietary Supplement: 25-gram oral fat load Dietary Supplement: 60-gram oral fat load |
Study Type: | Interventional |
Study Design: | Randomized, Open Label, Parallel Assignment |
Official Title: | Free Fatty Acids-Induced Hypertension and Endothelial Dysfunction in Obese Subjects |
Estimated Enrollment: | 12 |
Study Start Date: | August 2006 |
Estimated Study Completion Date: | August 2008 |
Estimated Primary Completion Date: | April 2008 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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2: Active Comparator
Intralipid 20% IV infusion at 20cc/hour
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Drug: Intralipid 20%
Intralipid 20% IV continuous infusion at 20cc/hour for 8 hours
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3: Active Comparator
Intralipid 20% IV infusion at 40cc/hour
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Drug: Intralipid 20%
Intralipid 20% IV continuous infusion at 40cc/hour for 8 hours
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4: Placebo Comparator
Normal Saline continuous IV infusion at 40cc/hour for 8 hours
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Drug: 0.9% Normal Saline
0.9% Normal Saline continuous IV infusion at 40/cc for 8 hours
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5: Active Comparator
25-gram oral fat load
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Dietary Supplement: 25-gram oral fat load
oral liquid fat load prepared by the GCRC every 2 hours for 8 hours.
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6: Active Comparator
60-gram oral fat load
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Dietary Supplement: 60-gram oral fat load
60-gram oral fat load intake every 2 hours for 8 hours
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1: Active Comparator
Intralipid 20% IV at 10cc/hour
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Drug: Intralipid 20% continuous IV infusion at 10cc/hour for 8 hours
Intralipid is an oil-in-water emulsion derived from egg phospholipids, soybean, and glycerol. The Intralipid 20% long-chain triglyceride emulsion contains: 200 g of soy bean oil; 12 g of egg yolk; 25 g of glycerol. The emulsion is composed of the following FFAs: linoleic acid: 50%, oleic acid: 26%, palmitic acid: 10%, stearic acid: 9%, egg yolk, phospholipids: 3.5%. The infusion of these long-chain triglyceride emulsions is generally considered to be a safe and have been in clinical practice since the 1980s offering important metabolic, immunologic, and nutritional advantages in critically ill patients
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Ages Eligible for Study: | 18 Years to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Contact: Guillermo Umpierrez, MD | 4047781665 | geumpie@emory.edu |
Contact: Dawn Smiley, MD | 4047781664 | dsmiley@emory.edu |
United States, Georgia | |
Grady Memorial Hospital | Recruiting |
Atlanta, Georgia, United States, 30303 | |
Contact: Guillermo Umpierrez, MD 404-778-1665 geumpie@emory.edu | |
Contact: Dawn Smiley, MD 4047781665 dsmiley@emory.edu | |
Principal Investigator: Guillermo Umpierrez, MD |
Principal Investigator: | Guillermo Umpierrez, MD | Emory University SOM/GCRC |
Responsible Party: | Emory University Schoolof Medicine ( Guillermo Umpierrez, MD ) |
Study ID Numbers: | 668-2006, IRB 668-2006 |
Study First Received: | December 28, 2007 |
Last Updated: | August 19, 2008 |
ClinicalTrials.gov Identifier: | NCT00589888 |
Health Authority: | United States: Institutional Review Board |
hypertension metabolic syndrome vascular reactivity Elevated blood pressure lipid toxicity |
Obesity Glycerol Vascular Diseases Palmitic Acid Hypertension |
Cardiovascular Diseases |