The Effect of a Peroxisome Proliferator-activated Receptor (PPAR) Alpha Agonist on Cytochrome P450 (CYP) Monooxygenase Activity in Humans
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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-hydroxyeicosatetraenoic acid(HETE) and epoxyeicosatrienoic acids(EET)s, 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.
    

Intervention name(s): fenofibrate; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Subjects will be randomized to receive either fenofibrate 160 mg/day or matching placebo for five days by mouth.; Subjects will be randomized to receive placebo or fenofibrate for five days by mouth
Other intervention name(s): Tricor
Intervention MeSH terms: Fenofibrate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Hypertension; Phenotyping; High Salt intake; frequently sampled IV glucose tolerance test(FSIVGTT); fenofibrate; epoxyeicosatrienoic acids; hydroxyeicosatetraenoic acids; dihydroxyeicosatrienoic acid; PPAR Alpha Agonist; CYP Monooxygenase Activity