FFA-Induced Hypertension and Endothelial Dysfunction

This study has been completed.
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Guillermo Umpierrez, Emory University
ClinicalTrials.gov Identifier:
NCT00589888
First received: December 28, 2007
Last updated: November 12, 2013
Last verified: July 2013

December 28, 2007
November 12, 2013
August 2006
April 2008   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00589888 on ClinicalTrials.gov Archive Site
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 ]
Same as current
Not Provided
Not Provided
 
FFA-Induced Hypertension and Endothelial Dysfunction
Free Fatty Acids-Induced Hypertension and Endothelial Dysfunction in Obese Subjects

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.

Not Provided
Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
  • Endothelial Dysfunction
  • Hypertension
  • 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
  • Drug: Intralipid 20%
    Intralipid 20% IV continuous infusion at 20cc/hour for 8 hours
  • Drug: Intralipid 20%
    Intralipid 20% IV continuous 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
  • Dietary Supplement: 32-gram oral fat load
    oral liquid fat load prepared by the GCRC every 2 hours for 8 hours.
  • Dietary Supplement: 64-gram oral fat load
    60-gram oral fat load intake every 2 hours for 8 hours
  • Active Comparator: 2
    Intralipid 20% IV infusion at 20cc/hour
    Intervention: Drug: Intralipid 20%
  • Active Comparator: 3
    Intralipid 20% IV infusion at 40cc/hour
    Intervention: Drug: Intralipid 20%
  • Placebo Comparator: 4
    Normal Saline continuous IV infusion at 40cc/hour for 8 hours
    Intervention: Drug: 0.9% Normal Saline
  • Active Comparator: 5
    32-gram oral fat load
    Intervention: Dietary Supplement: 32-gram oral fat load
  • Active Comparator: 6
    64-gram oral fat load
    Intervention: Dietary Supplement: 64-gram oral fat load
  • Active Comparator: 1
    Intralipid 20% IV at 10cc/hour
    Intervention: Drug: Intralipid 20% continuous IV infusion at 10cc/hour for 8 hours
Gosmanov AR, Smiley DD, Robalino G, Siquiera J, Khan B, Le NA, Patel RS, Quyyumi AA, Peng L, Kitabchi AE, Umpierrez GE. Effects of oral and intravenous fat load on blood pressure, endothelial function, sympathetic activity, and oxidative stress in obese healthy subjects. Am J Physiol Endocrinol Metab. 2010 Dec;299(6):E953-8. Epub 2010 Oct 5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
August 2008
April 2008   (final data collection date for primary outcome measure)

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.
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00589888
IRB00041116, IRB 668-2006
Yes
Guillermo Umpierrez, Emory University
Emory University
American Heart Association
Principal Investigator: Guillermo Umpierrez, MD Emory University SOM/GCRC
Emory University
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP