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

Emory University

Status: Completed

Conditions: Hypertension; Diabetes

Treatments: Drug: Placebo; Drug: Carvedilol; Drug: Salsalate; Drug: Intralipid 20%

Study type: Interventional

Funder types: Other

Identifiers

NCT02406586

IRB00009277a

Details and patient eligibility

About

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.

Full 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).

Enrollment: 36 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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36 participants in 3 patient groups, including a placebo group

Salsalate

Experimental group

Description:

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.

Treatment:

Drug: Intralipid 20%

Drug: Salsalate

Carvedilol

Experimental group

Description:

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.

Treatment:

Drug: Intralipid 20%

Drug: Carvedilol

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Intralipid 20%

Drug: Placebo