The Effect of a Peroxisome Proliferator-activated Receptor (PPAR) Alpha Agonist on Cytochrome P450 (CYP) Monooxygenase Activity in Humans
Condition: Hypertension
MeSH terms: Hypertension
Intervention: fenofibrate; Placebo
Intervention description: 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
Intervention MeSH terms: Fenofibrate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 75.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
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

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ambulatory subjects, 18-70 years of age, inclusive

          -  For female subjects, the following conditions must be met Postmenopausal status for at
             least 1 year, or Status post surgical sterilization, or If of childbearing potential,
             utilization of adequate birth control and willingness to undergo urine beta-hcg
             testing prior to drug treatment and on every study day

        Exclusion Criteria:

          -  Secondary causes of hypertension

          -  Diabetes type 1 or type 2 as defined by a fasting glucose of 126 mg/dl or greater or
             the use of anti-diabetic medication

          -  Use of hormone replacement therapy

          -  Statin or fibrate therapy

          -  A seated systolic blood pressure(SBP) greater than 179 mmHg or a seated diastolic
             blood pressure(DBP) greater than 110 mmHg

          -  Pregnancy

          -  Breast-feeding

          -  Cardiovascular disease such as history of myocardial infarction, presence of angina
             pectoris, significant arrhythmia, congestive heart failure, (LV hypertrophy
             acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart
             block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy

          -  Treatment with anticoagulants

          -  History of serious neurologic diseases such as cerebral hemorrhage,stroke, or
             transient ischemic attack

          -  History or presence of immunological or hematological disorders

          -  Diagnosis of asthma

          -  Clinically significant gastrointestinal impairment that could interfere with drug
             absorption

          -  Impaired hepatic function (aspartate aminotransferase [AST] and or alanine
             aminotransferase [ALT] > 2.0 x upper range)

          -  Known preexisting gallbladder disease

          -  Impaired renal function (eGFR < 60 ml/min/1.73M2)

          -  Hematocrit < 35%

          -  Any underlying or acute disease requiring regular medication which could possibly pose
             a threat to the subject or make implementation of the protocol or interpretation of
             the study results difficult

          -  Treatment with a glucocorticoid therapy

          -  Treatment with lithium salts

          -  History of of alcohol or drug abuse

          -  Treatment with any investigational drug in the 1 month preceding the study

          -  Mental conditions rendering the subject unable to understand the nature, scope and
             possible consequences of the study

          -  Inability to comply with the protocol, e.g uncooperative attitude, inability to return
             for follow-up visits, and unlikelihood of completing the study