FFA-Induced Hypertension and Endothelial Dysfunction

NCT00589888 | Completed Results DMC

• 2 other identifiers: IRB00041116IRB 668-2006
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Endothelial Dysfunction; Hypertension

Keywords

hypertension; metabolic syndrome; vascular reactivity; Elevated blood pressure; lipid toxicity

Outcome Measures

Primary Outcomes (5)

• Change in Systolic Blood Pressure to After Completing an 8-hour Normal Saline Infusion in Obese Normotensive Subjects.

  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 patient was in Supine position. The Blood pressure was measured at admission and at end of the fat load. The BP from the admission are compared to BP after the fat load. A normal systolic blood pressure is lower than 120 mmHg; elevated blood pressure if the systolic reading is 120-129 mmHg. A level above 140 mmHg is considered hypertension.

  Baseline and at the end of the 8-hours

• Change in Systolic Blood Pressure From Baseline to After Completing an 8-hour 20% Intralipid @ 20cc/hr Infusion in Obese Normotensive Subjects.

  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 admission when patient was in Supine position. The Blood pressure was measured at admission and at every 2 hours till the end of infusion. The BP from the admission are compared to BP after the infusion.A normal systolic blood pressure is lower than 120 mmHg; elevated blood pressure if the systolic reading is 120-129 mmHg. A level above 140 mmHg is considered hypertension.

  Baseline and at the end of the 8-hours

• Changes in Systolic Blood Pressure From Baseline to After Completing an 8-hour 20% Intralipid @ 40cc/hr Infusion in Obese Normotensive Subjects

  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 admission when patient was in Supine position. The Blood pressure was measured at admission and at every 2 hours till the end of infusion. The BP from the admission are compared to BP after the infusion. A normal systolic blood pressure is lower than 120 mmHg; elevated blood pressure if the systolic reading is 120-129 mmHg. A level above 140 mmHg is considered hypertension.

  Baseline and at the end of the 8-hours

• Change in Systolic Blood Pressure From Baseline to After Completing an Oral 32-gram Fat Load in Obese Normotensive Subjects.

  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 patient was in Supine position.The Blood pressure was measured at admission and at end of the fat load. The BP from the admission are compared to BP after the fat load. A normal systolic blood pressure is lower than 120 mmHg; elevated blood pressure if the systolic reading is 120-129 mmHg. A level above 140 mmHg is considered hypertension.

  Baseline and at the end of the 8-hours

• Changes in Systolic Blood Pressure From Baseline to After Completing an Oral 64-gram Fat Load in Obese Normotensive Subjects

  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 patient was in Supine position. The Blood pressure was measured at admission and at end of the fat load. The BP from the admission are compared to BP after the fat load. A normal systolic blood pressure is lower than 120 mmHg; elevated blood pressure if the systolic reading is 120-129 mmHg. A level above 140 mmHg is considered hypertension.

  at the end of the 8 hours

Secondary Outcomes (4)

• Change in Flow-mediated Dilation (FMD) of Endothelium-dependent Brachial Artery From Baseline to After Completing a Specific Intervention in Obese Normotensive Subjects.

  Baseline and at the end of the 8-hours

• Change in Blood Glucose Levels From Baseline to 6-8 Hours After Intervention Among Obese Healthy Subjects

  Baseline and at the end of the 8-hours

• Change in C-peptide Concentration Levels From Baseline to After Specific Intervention Among the Healthy Obese Subjects

  baseline and after 8 hours after admission

• Change in Blood Insulin Levels From Baseline to After Intervention Among the Normal Obese Subjects

  Baseline and at the end of the 8-hours

Study Arms (5)

Intralipid 20%@ 20cc/hour

ACTIVE COMPARATOR

Intralipid 20% IV infusion at 20cc/hour

Drug: Intralipid 20% @ 20cc/hour

Intralipid 20% @ 40cc/hour

ACTIVE COMPARATOR

Intralipid 20% IV infusion at 40cc/hour

Drug: Intralipid 20%@ 40cc/hour

Normal Saline infusion @ 40cc/hour

PLACEBO COMPARATOR

Normal Saline continuous IV infusion at 40cc/hour for 8 hours

Drug: Normal Saline

32-gram oral fat load

ACTIVE COMPARATOR

32-gram oral fat load once

Dietary Supplement: 32-gram oral fat load

64-gram oral fat load

ACTIVE COMPARATOR

64-gram oral fat load once

Dietary Supplement: 64-gram oral fat load

Interventions

Intralipid 20% @ 20cc/hour DRUG

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

Also known as: 20% i.v. fat emulsion

Intralipid 20%@ 20cc/hour

Intralipid 20%@ 40cc/hour DRUG

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.

Also known as: 20% i.v. fat emulsion

Intralipid 20% @ 40cc/hour

Normal Saline DRUG

In this arm subjects received 0.9% Normal Saline continuous IV infusion at 40/cc for 8 hours.

Also known as: 0.9% Sodium Chloride

Normal Saline infusion @ 40cc/hour

32-gram oral fat load DIETARY_SUPPLEMENT

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.

32-gram oral fat load

64-gram oral fat load DIETARY_SUPPLEMENT

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.

64-gram oral fat load

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead
• American Heart Association: collaborator

Study Sites (1)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Related Publications (1)

• 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 RESULT

MeSH Terms

Conditions

Hypertension; Metabolic Syndrome

Interventions

soybean oil, phospholipid emulsion; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

The study subjects were mostly African-Americans, precluding generalization of the findings to other ethnic groups. Study was of short duration, and the composition of oral fat load was not identical to the intralipid composition.

Results Point of Contact

• Title: Guillermo Umpierrez, MD
• Organization: Emory Univ SOM

geumpie@emory.edu

4047781665

Study Officials

• Guillermo Umpierrez, MD

  Emory University SOM/GCRC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: December 28, 2007
• First Posted: January 10, 2008
• Study Start: August 1, 2006
• Primary Completion: April 1, 2008
• Study Completion: August 1, 2008
• Last Updated: October 16, 2018
• Results First Posted: July 9, 2014

Record last verified: 2018-09

Locations

US (1)