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: June 6, 2014
Last verified: May 2014
  Purpose

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%
Drug: 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

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Change in Systolic Blood Pressure [ Time Frame: at the end of the 8-hours ] [ Designated as safety issue: No ]
    systolic blood pressure change from baseline during an 8-hour normal saline infusion in obese normotensive subjects.

  • Change in Systolic Blood Pressure [ Time Frame: at the end of 8 hours ] [ Designated as safety issue: No ]
    systolic blood pressure change from baseline during an 8-hour 20% intralipid @ 20cc/hr infusion in obese normotensive subjects.

  • Changes in Systolic Blood Pressure [ Time Frame: at the end of 8 hours ] [ Designated as safety issue: No ]
    BP change from baseline during an 8-hour 20% intralipid @ 40cc/hr infusion in obese normotensive subjects.

  • Changes in Systolic Blood Pressure From Baseline [ Time Frame: at the end of 8 hours ] [ Designated as safety issue: No ]
    systolic blood pressure change from baseline during an oral 32-gram fat load in obese normotensive subjects.

  • Changes in Systolic Blood Pressure [ Time Frame: at the end of the 8 hours ] [ Designated as safety issue: No ]
    systolic blood pressure change from baseline during an oral 64-gram fat load in obese normotensive subjects.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 13
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: Intralipid 20%@ 20cc/hour
Intralipid 20% IV infusion at 20cc/hour
Drug: Intralipid 20%
Intralipid 20% IV continuous infusion at 20cc/hour for 8 hours
Active Comparator: Intralipid 20% @ 40cc/hour
Intralipid 20% IV infusion at 40cc/hour
Drug: Intralipid 20%
Intralipid 20% IV continuous infusion at 40cc/hour for 8 hours
Placebo Comparator: Normal Saline infusion @ 40cc/hour
Normal Saline continuous IV infusion at 40cc/hour for 8 hours
Drug: Normal Saline
0.9% Normal Saline continuous IV infusion at 40/cc for 8 hours
Active Comparator: 32-gram oral fat load
32-gram oral fat load once
Dietary Supplement: 32-gram oral fat load
oral liquid fat load prepared by the GCRC every 2 hours for 8 hours.
Active Comparator: 64-gram oral fat load
64-gram oral fat load once
Dietary Supplement: 64-gram oral fat load
60-gram oral fat load intake every 2 hours for 8 hours

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00589888

Locations
United States, Georgia
Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
Sponsors and Collaborators
Emory University
American Heart Association
Investigators
Principal Investigator: Guillermo Umpierrez, MD Emory University SOM/GCRC
  More Information

Publications:
Responsible Party: Guillermo Umpierrez, Professor of Medicine, Emory University
ClinicalTrials.gov Identifier: NCT00589888     History of Changes
Other Study ID Numbers: IRB00041116, IRB 668-2006
Study First Received: December 28, 2007
Results First Received: March 24, 2014
Last Updated: June 6, 2014
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 July 28, 2014