Clinical trial NCT02406586: Free Fatty Acids-Induced Hypertension in Obese Subjects (Aim #2)
Official title: Free Fatty Acids-Induced Hypertension, Endothelial Dysfunction, Inflammation, Insulin Resistance, and Autonomic Dysfunction in Lean and Obese Subjects (Aim #2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Diabetes
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: American Diabetes Association
First posted: 2015-04-02
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

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

Primary outcomes:
measure: Change in Systolic Blood Pressure.
timeFrame: Pre-dose (Baseline), within 4 hours at Baseline visit
measure: Change in Systolic Blood Pressure
timeFrame: Pre-dose (Baseline), within 8 hours at Baseline visit
measure: Change in Systolic Blood Pressure
timeFrame: Pre-dose (Baseline), within 12 hours at Baseline visit
measure: Change in Systolic Blood Pressure
timeFrame: Pre-dose (Baseline), within 16 hours at Baseline visit
measure: Change in Systolic Blood Pressure
timeFrame: Pre-dose (Baseline), within 20 hours at Baseline visit
measure: Change in Systolic Blood Pressure
timeFrame: Pre-dose (Baseline), within 24 hours at Baseline visit
measure: Change in Systolic Blood Pressure
timeFrame: Pre-dose (Week 6), within 4 hours at Week 6 visit
measure: Change in Systolic Blood Pressure
timeFrame: Pre-dose (Week 6), within 8 hours at Week 6 visit
measure: Change in Systolic Blood Pressure
timeFrame: Pre-dose (Week 6), within 12 hours at Week 6 visit
measure: Change in Systolic Blood Pressure
timeFrame: Pre-dose (Week 6), within 16 hours at Week 6 visit
measure: Change in Systolic Blood Pressure
timeFrame: Pre-dose (Week 6), within 20 hours at Week 6 visit
measure: Change in Systolic Blood Pressure
timeFrame: Pre-dose (Week 6), within 24 hours at Week 6 visit
measure: Change in Flow-mediated Dilation
timeFrame: Pre-dose (Baseline), within 12 hours at Baseline visit
measure: Change in Flow-mediated Dilation
timeFrame: Pre-dose (Baseline), within 24 hours at Baseline visit
measure: Change in Flow-mediated Dilation
timeFrame: Pre-dose (Week 6), within 12 hours at Week 6 visit
measure: Change in Flow-mediated Dilation
timeFrame: Pre-dose (Week 6), within 24 hours at Week 6 visit
Secondary outcomes:
measure: Change in Diastolic Blood Pressure From Baseline to 6 Weeks
timeFrame: Baseline, 6 weeks
measure: Change in Oxidative Stress Markers.
timeFrame: Baseline, 6 weeks
measure: Change in Augmentation Index (AIx)
timeFrame: Baseline, 6 weeks
measure: Change in Expression of Inflammatory Biomarker Interleukin-6 (IL-6)
timeFrame: Baseline, 6 weeks
measure: Change in FFA (Free Fatty Acid) Levels From Baseline to 6 Weeks
timeFrame: Baseline, 6 weeks
measure: Change in Pulse Wave Velocity (PWV)
timeFrame: Baseline, 6 weeks
measure: Change in Expression of Inflammatory Biomarker C-Reactive Protein (CRP)
timeFrame: Baseline, 6 weeks
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Guillermo Umpierrez, MD
role: PRINCIPAL_INVESTIGATOR
References: