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Atlanta, Georgia 30303


Purpose:

The study is a prospective open label study to examine the effects of oral and intravenous fat load on blood pressure, endothelial function, sympathetic activity, and oxidative stress in obese healthy subjects. Subjects will receive either 8-hour of intravenous or oral fat loads in either low or high doses or normal saline in random order. Blood samples are drawn and vitals are measured before and after the infusions. Endothelial function and plasma glucose and lipid levels are measured to study the effects.


Study summary:

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 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.


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.


Study is Available At:


Original ID:

IRB00041116


NCT ID:

NCT00589888


Secondary ID:

IRB 668-2006


Study Acronym:


Brief Title:

FFA-Induced Hypertension and Endothelial Dysfunction


Official Title:

Free Fatty Acids-Induced Hypertension and Endothelial Dysfunction in Obese Subjects


Overall Status:

Completed


Study Phase:

N/A


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

65 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Emory University


Oversight Authority:

United States: Institutional Review Board


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

5


Number of Groups:

0


Total Enrollment:

13


Enrollment Type:

Actual


Overall Contact Information

Official Name:Guillermo Umpierrez, MD
Principal Investigator
Emory University SOM/GCRC

Study Dates

Start Date:August 2006
Completion Date:August 2008
Completion Type:Actual
Primary Completion Date:April 2008
Primary Completion Type:Actual
Verification Date:September 2018
Last Changed Date:September 20, 2018
First Received Date:December 28, 2007
First Results Date:March 24, 2014

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Change in Blood Insulin Levels From Baseline to After Intervention Among the Normal Obese Subjects
Time Frame:Baseline and at the end of the 8-hours
Safety Issues:False
Description:Insulin is an anabolic hormone that promotes glucose uptake, glycogenesis, lipogenesis, and protein synthesis of skeletal muscle and fat tissue through the tyrosine kinase receptor pathway. In addition, insulin is the most important factor in the regulati
Outcome Type:Secondary Outcome
Measure:Change in C-peptide Concentration Levels From Baseline to After Specific Intervention Among the Healthy Obese Subjects
Time Frame:baseline and after 8 hours after admission
Safety Issues:False
Description:C-peptide is a peptide composed of 31 amino acids. It is released from the pancreatic beta-cells during cleavage of insulin from proinsulin. It is mainly excreted by the kidney, and its half-life is 3-4 times longer than that of insulin. The reference ran
Outcome Type:Secondary Outcome
Measure:Change in Blood Glucose Levels From Baseline to 6-8 Hours After Intervention Among Obese Healthy Subjects
Time Frame:Baseline and at the end of the 8-hours
Safety Issues:False
Description:The blood glucose level is the amount of glucose present in the blood of humans. Many factors affect a person's blood sugar level. The body's homeostatic mechanism of blood sugar regulation (known as glucose homeostasis), when operating normally, restores
Outcome Type:Secondary Outcome
Measure:Change in Flow-mediated Dilation (FMD) of Endothelium-dependent Brachial Artery From Baseline to After Completing a Specific Intervention in Obese Normotensive Subjects.
Time Frame:Baseline and at the end of the 8-hours
Safety Issues:False
Description:Endothelium-dependent brachial artery dilatation was assessed as a measurement of endothelial function using established methodology. Briefly, ultrasound images of the brachial artery were obtained at baseline under standardized conditions and 60 s after
Outcome Type:Primary Outcome
Measure:Changes in Systolic Blood Pressure From Baseline to After Completing an Oral 64-gram Fat Load in Obese Normotensive Subjects
Time Frame:at the end of the 8 hours
Safety Issues:False
Description:To study the effects of high dose oral fat load on systolic blood pressure (SBP) in healthy obese subjects, subject's baseline SBP is compared to SBP after the infusion. Blood Pressure (BP) was measured with a manual cuff in triplicate on admission when p
Outcome Type:Primary Outcome
Measure:Change in Systolic Blood Pressure From Baseline to After Completing an Oral 32-gram Fat Load in Obese Normotensive Subjects.
Time Frame:Baseline and at the end of the 8-hours
Safety Issues:False
Description:To study the effects of oral low dose fat load on systolic blood pressure (SBP) in healthy obese subjects, subject's baseline SBP is compared to SBP after the infusion. Blood Pressure (BP) was measured with a manual cuff in triplicate on admission when pa
Outcome Type:Primary Outcome
Measure:Changes in Systolic Blood Pressure From Baseline to After Completing an 8-hour 20% Intralipid @ 40cc/hr Infusion in Obese Normotensive Subjects
Time Frame:Baseline and at the end of the 8-hours
Safety Issues:False
Description:To study the effects of high dose intravenous (IV) fat infusion on systolic blood pressure (SBP) in healthy obese subjects, subject's baseline SBP is compared to SBP after the infusion. Blood Pressure (BP) was measured with a manual cuff in triplicate on
Outcome Type:Primary Outcome
Measure:Change in Systolic Blood Pressure From Baseline to After Completing an 8-hour 20% Intralipid @ 20cc/hr Infusion in Obese Normotensive Subjects.
Time Frame:Baseline and at the end of the 8-hours
Safety Issues:False
Description:To study the effects of low dose intravenous (IV) fat infusion on systolic blood pressure (SBP) in healthy obese subjects, subject's baseline SBP is compared to SBP after the infusion. Blood Pressure (BP) was measured with a manual cuff in triplicate on a
Outcome Type:Primary Outcome
Measure:Change in Systolic Blood Pressure to After Completing an 8-hour Normal Saline Infusion in Obese Normotensive Subjects.
Time Frame:Baseline and at the end of the 8-hours
Safety Issues:False
Description:To study the effects of high dose oral fat load on systolic blood pressure (SBP) in healthy obese subjects, subject's baseline SBP is compared to SBP after the infusion. Blood Pressure (BP) was measured with a manual cuff in triplicate on admission when p

Study Interventions

Intervention Type:Drug
Name:Intralipid 20% @ 20cc/hour
Description:In this arm subjects received Intralipid 20% Intravenous IV continuous infusion at 20cc/hour for 8 hours. The 20% intralipid solution is a long-chain triglyceride emulsion composed of 50% polyunsaturated fatty acids, 26% monounsaturated fatty acids, and 19% saturated fatty acids. During the intralipid infusion studies, subjects remained fasting
Arm Name:Intralipid 20%@ 20cc/hour
Other Name:20% i.v. fat emulsion
Intervention Type:Drug
Name:Intralipid 20%@ 40cc/hour
Description:In this arm subjects received Intralipid 20% IV continuous infusion at 40cc/hour for 8 hours. In this arm subjects will receive Intralipid 20% Intravenous IV continuous infusion at 20cc/hour for 8 hours. The 20% intralipid solution is a long-chain triglyceride emulsion composed of 50% polyunsaturated fatty acids, 26% monounsaturated fatty acids, and 19% saturated fatty acids. During the intralipid infusion studies, subjects remained fasting.
Arm Name:Intralipid 20% @ 40cc/hour
Other Name:20% i.v. fat emulsion
Intervention Type:Drug
Name:Normal Saline
Description:In this arm subjects received 0.9% Normal Saline continuous IV infusion at 40/cc for 8 hours.
Arm Name:Normal Saline infusion @ 40cc/hour
Other Name:0.9% Sodium Chloride
Intervention Type:Dietary Supplement
Name:32-gram oral fat load
Description:In this arm subjects received oral liquid fat load prepared by the General Clinical Research Center (GCRC) at baseline and every 2 hours for 6 hours. Participants received fat with Free Fatty Acids (FFA) composed of 33% polyunsaturated fatty acids, 34% monounsaturated fatty acids, and 22% saturated fatty acids. The oral fat load in either low or high dose was given in four equally divided doses at 0, 2, 4, and 6 h.
Arm Name:32-gram oral fat load
Intervention Type:Dietary Supplement
Name:64-gram oral fat load
Description:In this arm subjects received 60-gram oral fat load intake at baseline and every 2 hours for 6 hours prepared by the General Clinical Research Center (GCRC). Participants received fat with Free Fatty Acids (FFA) composed of 33% polyunsaturated fatty acids, 34% monounsaturated fatty acids, and 22% saturated fatty acids. The oral fat load in either low or high dose was given in four equally divided doses at 0, 2, 4, and 6 h.
Arm Name:64-gram oral fat load

Study Arms

Study Arm Type:Active Comparator
Arm Name:Intralipid 20%@ 20cc/hour
Description:Intralipid 20% IV infusion at 20cc/hour
Study Arm Type:Active Comparator
Arm Name:Intralipid 20% @ 40cc/hour
Description:Intralipid 20% IV infusion at 40cc/hour
Study Arm Type:Placebo Comparator
Arm Name:Normal Saline infusion @ 40cc/hour
Description:Normal Saline continuous IV infusion at 40cc/hour for 8 hours
Study Arm Type:Active Comparator
Arm Name:32-gram oral fat load
Description:32-gram oral fat load once
Study Arm Type:Active Comparator
Arm Name:64-gram oral fat load
Description:64-gram oral fat load once

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Emory University
Agency Class:Other
Agency Type:Collaborator
Agency Name:American Heart Association

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation: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. doi: 10.1152/ajpendo.00469.2010. Epub 2010 Oct 5.
PMID:20923960

Data Source: ClinicalTrials.gov

Date Processed: August 31, 2019

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