FFA-Induced Hypertension and Endothelial Dysfunction
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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 |
---|---|
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: 32-gram oral fat load Dietary Supplement: 64-gram oral fat load |
Study Type: | Interventional |
Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label |
Official Title: | Free Fatty Acids-Induced Hypertension and Endothelial Dysfunction in Obese Subjects |
- The primary outcome of interest are changes in BP and endothelial function (FMD, Arterial Compliance, PWA, HRV) during an 8-hour Intralipid infusion (dose-response) and normal saline infusion in obese normotensive subjects. [ Time Frame: Changes in BP assessed every 2 hours during the 8 hours study; Lipid changes assessed every 2 hours during the 8-hour study, and Flow-mediated dilatation, peripheral compliance, PWA, and HRV assessed at 0,4, and 8 hours ] [ Designated as safety issue: No ]
- The secondary outcomes of interest are the effects of increased FFAs on BP, endothelial function and inflammatory markers after oral fat load (chylomicron pathway) versus IV administration of Intralipid infusion in obese normotensive subjects. [ Time Frame: Changes in BP assessed every 2 hours during the 8 hours study; Lipid changes assessed every 2 hours during the 8-hour study, and Flow-mediated dilatation, peripheral compliance, PWA, and HRV assessed at 0,4, and 8 hours ] [ Designated as safety issue: No ]
Estimated Enrollment: | 12 |
Study Start Date: | August 2006 |
Study Completion Date: | August 2008 |
Primary Completion Date: | April 2008 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
Active Comparator: 2
Intralipid 20% IV infusion at 20cc/hour
|
Drug: Intralipid 20%
Intralipid 20% IV continuous infusion at 20cc/hour for 8 hours
|
Active Comparator: 3
Intralipid 20% IV infusion at 40cc/hour
|
Drug: Intralipid 20%
Intralipid 20% IV continuous infusion at 40cc/hour for 8 hours
|
Placebo Comparator: 4
Normal Saline continuous IV infusion at 40cc/hour for 8 hours
|
Drug: 0.9% Normal Saline
0.9% Normal Saline continuous IV infusion at 40/cc for 8 hours
|
Active Comparator: 5
32-gram oral fat load
|
Dietary Supplement: 32-gram oral fat load
oral liquid fat load prepared by the GCRC every 2 hours for 8 hours.
|
Active Comparator: 6
64-gram oral fat load
|
Dietary Supplement: 64-gram oral fat load
60-gram oral fat load intake every 2 hours for 8 hours
|
Active Comparator: 1
Intralipid 20% IV at 10cc/hour
|
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
|
Ages Eligible for Study: | 18 Years to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Males or females between the ages of 18 and 65 years.
- Definition: obese = BMI ≥ 30 kg/m2
- Blood pressure < 140/80 mm Hg and no prior history of hypertension
Exclusion Criteria:
- History of hypertension or previous history of antihypertensive drug therapy.
- Current tobacco use
- Fasting triglyceride levels > 250 mg/dL during the stabilization period.
- Liver disease (ALT 2.5x > upper limit of normal), or other significant medical or surgical illness, including myocardial ischemia, congestive heart failure, liver failure, and infectious processes.
- Serum creatinine ≥1.5 mg/dL for males, or ≥ 1.4 mg/dL for females.
- History of drug or alcohol abuse within the last 5 years.
- Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
- Female subjects are pregnant or breast feeding at time of enrollment into the study.
United States, Georgia | |
Grady Memorial Hospital | |
Atlanta, Georgia, United States, 30303 |
Principal Investigator: | Guillermo Umpierrez, MD | Emory University SOM/GCRC |
Publications:
Responsible Party: | Guillermo Umpierrez, MD, Emory University Schoolof Medicine |
ClinicalTrials.gov Identifier: | NCT00589888 History of Changes |
Other Study ID Numbers: | 668-2006, IRB 668-2006 |
Study First Received: | December 28, 2007 |
Last Updated: | March 7, 2011 |
Health Authority: | United States: Institutional Review Board |
Keywords provided by Emory University:
hypertension metabolic syndrome vascular reactivity Elevated blood pressure lipid toxicity |
Additional relevant MeSH terms:
Hypertension Vascular Diseases Cardiovascular Diseases |
ClinicalTrials.gov processed this record on October 17, 2012