The Effect of a Peroxisome Proliferator-activated Receptor (PPAR) Alpha Agonist on Cytochrome P450 (CYP) Monooxygenase Activity in Humans
The hypothesis is to test to see if the drug fenofibrate will increase important chemicals in the body and specifically in the kidney, help to rid the body of salt by the kidneys, decrease blood pressure and improve insulin sensitivity during high-salt intake in individuals with hypertension.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||The Effect of a PPAR Alpha Agonist on CYP Monooxygenase Activity in Humans|
- Focus on the effects of fenofibrate during high-salt intake on blood pressure twenty-four hour 20-HETE, EET and DHET excretion, renal blood flow and net sodium excretion and Aldosterone to renin ratio. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- Focus on the effect of fenofibrate on insulin sensitivity, glucose effectiveness, beta cell function and HDL-cholesterol. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
|Study Start Date:||September 2009|
|Estimated Study Completion Date:||December 2012|
|Estimated Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
Active Comparator: 1
Randomized study of fenofibrate during high salt diet
Subjects will be randomized to receive either fenofibrate 160 mg/day or matching placebo for five days by mouth.
Other Name: Tricor
Placebo Comparator: 2
Placebo verses fenofibrate
Subjects will be randomized to receive placebo or fenofibrate for five days by mouth
Other Name: Placebo
Hypertension affects 73 million people in the United States and a billion people worldwide and contributes to death due to stroke, myocardial infarction, end-stage kidney disease and congestive heart failure. Fifty to 60% of individuals with hypertension have "salt-sensitive" hypertension, characterized by an exaggerated blood pressure response to increased salt intake. Salt-sensitive hypertension is associated with increased mortality due to cardiovascular disease.
This study will test the hypothesis that administration of a PPARa agonist, an intervention increases renal tubular Cyp2c and 4a expression in rodents, will increase urinary excretion of 20-HETE and EETs, induce natriuresis, decrease blood pressure, and improve insulin sensitivity during high-salt intake in individuals with hypertension.
Metabolites of the P450 arachidonic acid monooxygenases play an important role in the regulation of blood pressure in rodent models.
Targeted disruption of murine Cyp4a genes provides insight into the roles of renal monooxygenases and epoxygenases in the regulation of salt excretion and blood pressure.
PPARa agonists induce the expression of renal tubular monoxygenases and epoxygenases and decrease blood pressure in both Ang II- dependent and salt-sensitive rodent models of hypertension.
PPARa agonists have been reported to reduce blood pressure in clinical trials in humans. The effect of PPARa agonist on renal vasodilation, sodium excretion and excretion of urinary epoxygenase or monooxygenase products in response to salt loading is not known.
The regulation of urinary 20-HETE excretion may be impaired in human hypertension.
|Contact: Delia M Woods, BSNemail@example.com|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37232|
|Contact: Carol Bowling, BSN 615-322-8837 firstname.lastname@example.org|
|Principal Investigator: Nancy J Brown, MD|
|Sub-Investigator: Kimberly Gilbert, MD|
|Principal Investigator:||Nancy J Brown, MD||Vanderbilt University|