Free Fatty Acids-Induced Hypertension in Obese Subjects (Aim #2)

NCT ID: NCT02406586

Last Updated: 2019-01-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2011-03-31

Brief Summary

The purpose of this study is to see if salsalate, an Nuclear factor-kappaB (NF-κB) mediated inflammation inhibitor, or carvedilol, an α- and β-blocker, will protect against free fatty acid induced hypertension, insulin resistance, endothelial dysfunction, inflammation and oxidative stress, and autonomic dysfunction in obese normotensive subjects.

Detailed Description

During postprandial lipemia, dietary triglycerides transported by intestinal chylomicrons are hydrolyzed by lipoprotein lipase lining the vascular bed, with subsequent release of FFA for transport across the endothelium. Whether the intermittent flux of FFA has the same impact as the i.v. lipid infusion will be examined. Decreased endothelial function has been reported after a single or long-term dietary high fat load in normal subjects; however, others have found no effects on brachial artery vasoreactivity. Our preliminary studies indicate that high oral fat loads (60 g) resulted in higher FFA levels and BP changes, and reduced FMD compared to low fat load (25 g).

Conditions

Hypertension; Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Salsalate

Obese, normotensive, healthy subjects will receive an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject has no side effects, the dose will be increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects will then receive another 24-hour IV administration of Intralipid 20% at the 6-week point.

Group Type: EXPERIMENTAL

Salsalate

Intervention Type: DRUG

Salsalate 750 mg

Intralipid 20%

Intervention Type: DRUG

24-hour infusion of Intralipid 20% solution at 20 mL/h (96 g/24 h)

Carvedilol

Obese, normotensive, healthy subjects will receive an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject has no side effects, the dose will be increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects will then receive another 24-hour IV administration of Intralipid 20% at the 6-week point.

Group Type: EXPERIMENTAL

Carvedilol

Intervention Type: DRUG

Carvedilol 3.125 mg

Intralipid 20%

Intervention Type: DRUG

24-hour infusion of Intralipid 20% solution at 20 mL/h (96 g/24 h)

Placebo

Obese, normotensive, healthy subjects will receive an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose will be increased to two placebo tablets twice daily for the remaining four weeks. The subjects will then receive another 24-hour IV administration of Intralipid 20% at the 6-week point.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

One tablet

Intralipid 20%

Intervention Type: DRUG

24-hour infusion of Intralipid 20% solution at 20 mL/h (96 g/24 h)

Interventions

Salsalate

Salsalate 750 mg

Intervention Type: DRUG

Carvedilol

Carvedilol 3.125 mg

Intervention Type: DRUG

Placebo

One tablet

Intervention Type: DRUG

Intralipid 20%

24-hour infusion of Intralipid 20% solution at 20 mL/h (96 g/24 h)

Intervention Type: DRUG

Other Intervention Names

Disalcid; NSAID; Coreg; 20% I.V. Fat Emulsion

Eligibility Criteria

Inclusion Criteria

• Males or females
• Obese subjects (body mass index (BMI) ≥ 30 kg/m^2)
• 18 and 65 years
• Blood pressure reading < 140/80 mm Hg and no prior history of hypertension

Exclusion Criteria

• History of diabetes mellitus
• History of 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

American Diabetes Association

OTHER

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Guillermo Umpierrez, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Guillermo Umpierrez, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Grady Memorial Hospital

Atlanta, Georgia, United States

Countries

United States

Other Identifiers

IRB00009277a

Identifier Type: -

Identifier Source: org_study_id