FFA Hypertension and Inflammation in Lean and Obese Subjects (FFAADA)

This study has been completed.
Sponsor:
Collaborator:
American Diabetes Association
Information provided by (Responsible Party):
Guillermo Umpierrez, Emory University
ClinicalTrials.gov Identifier:
NCT00721617
First received: June 26, 2008
Last updated: February 7, 2014
Last verified: February 2014
  Purpose

Our recent studies indicate that increased levels of a circulating fat (free fatty acids or FFAs) increases blood pressure, impairs endothelial (vascular) function, and increases inflammatory markers in subjects with and without diabetes. The effects of FFA on blood pressure and vasculature 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. In addition, it is not known 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. This study has two parts.


Condition Intervention
Diabetes
Hypertension
Obesity
Drug: Intravenous Infusions with Intralipid 20%, normal saline and liquid fat
Drug: Intravenous Infusions with Intralipid 20%

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Free Fatty Acids-Induced Hypertension, Endothelial Dysfunction, Inflammation, Insulin Resistance, and Autonomic Dysfunction in Lean and Obese Subjects

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • To determine the effects of increasing FFA on BP, endothelial function, vascular inflammatory markers, oxidative stress, and sympathetic nervous system activity in obese normotensive subjects. [ Time Frame: once all subjects have been recruited ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine in mechanistic studies whether the FFA-induced "acute MetS" can be modulated by pathways involving NF-B-mediated inflammation, or autonomic activation. [ Time Frame: once all subjects have been recruited ] [ Designated as safety issue: Yes ]

Enrollment: 15
Study Start Date: April 2009
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
during 3 visits 12 lean subjects will be given separate 24 hour challenges with i.v. saline (control), i.v. Intralipid 20% solution at 20 mL/h (96 g/24 h), and oral fat load of 96 g/24 h.
Drug: Intravenous Infusions with Intralipid 20%, normal saline and liquid fat
Research subjects will receive, in random order, a 24-hour intravenous (IV) infusion of Intralipid 20% at 20ml/hr (a fat solution), 24-hour IV infusion of normal saline, or an oral liquid fat diet every 4 hours for 24-hours.
Placebo Comparator: 2
Twelve obese nondiabetic and normotensive subjects will be randomized to receive salsalate, carvedilol or placebo for 6 weeks (total of 36 subjects). Study subjects may be those who participated in Aim 1 or a second cohort of subjects. Subjects who participated in Aim 1 will be randomized following completion of baseline (Aim 1) studies.
Drug: Intravenous Infusions with Intralipid 20%
Twelve obese nondiabetic and normotensive subjects will be randomized to receive salsalate, carvedilol or placebo for 6 weeks (total of 36 subjects). Study subjects may be those who participated in Aim 1 or a second cohort of subjects. Subjects who participated in Aim 1 will be randomized following completion of baseline (Aim 1) studies.

Detailed Description:

In the first part of the study, a group of 12 obese and 12 lean nondiabetic, normotensive subjects will be admitted to the Grady Clinical Research Center (GCRC) on separate 3 occasions. Research subjects will receive, in random order, a 24-hour intravenous (IV) infusion of Intralipid 20ml/hr (a fat solution), 24-hour IV infusion of normal saline, or an oral liquid fat diet every 4 hours for 24-hours. The effect of increased FFAs on blood pressure and endothelial (vascular) function via intravenous infusion versus oral fat load therapy will be assessed. The fat load (IV vs. oral) that causes the largest effect on blood pressure and endothelial function will be used in the second portion of the protocol.

In the second part of the study, a group of 36 obese normotensive (diabetic and nondiabetic) subjects will be admitted to the GCRC on 2 separate occasions for a randomized control trial. Study subjects will first be admitted to receive a fat load and then they will be randomly placed on either salsalate, carvedilol, or placebo for 6 weeks. After the 6-week intervention period, the subjects will be re-admitted to the GCRC to see if the intervention has any effect on improving blood pressure or endothelial function.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Males or females, obese subjects (BMI ≥ 30 kg/m2), between the ages of 18 and 65 years
  • A BP < 140/80 mm Hg and no prior history of hypertension.

Exclusion Criteria:

  • History of diabetes mellitus, hypertension, fasting triglyceride levels > 250 mg/dL, liver disease (ALT 2.5x > upper limit of normal),
  • serum creatinine ≥1.5 mg/dL,
  • smokers, drug or alcohol abuse,
  • mental condition rendering the subject unable to understand the scope and possible consequences of the study,
  • female subjects who are pregnant or breast feeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00721617

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

No publications provided

Responsible Party: Guillermo Umpierrez, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT00721617     History of Changes
Other Study ID Numbers: IRB00009277
Study First Received: June 26, 2008
Last Updated: February 7, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
Diabetes
Hypertension
Obesity

Additional relevant MeSH terms:
Hypertension
Obesity
Inflammation
Vascular Diseases
Cardiovascular Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Pathologic Processes

ClinicalTrials.gov processed this record on October 19, 2014