Uric Acid in Essential Hypertension in Children
Condition: Essential Hypertension
MeSH terms: Hypertension; Essential Hypertension
Study type: Interventional
Phase: Phase 2

Summary: 
      The study is a randomized, double-blinded, placebo controlled, crossover trial of allopurinol
      for the treatment of children with newly diagnosed essential hypertension.
    

Detailed description: 
      The study will be a double-blinded crossover trial. We will recruit 40 children between the
      ages of 12 and 18 years, from the pediatric renal and hypertension programs at Texas
      Children's Hospital. The study consists of four phases, a screening phase a treatment phase,
      an interim washout phase and a crossover phase.

      The screening phase will last between 1 and 2 weeks. Patients will be provided with a digital
      blood pressure monitor with an appropriately sized cuff and be instructed to perform daily
      blood pressure measurements and keep a blood pressure log. This will detect severe
      hypertension that needs immediate attention and identify patients or families in which
      compliance problems likely to compromise data collection. Blood tests will be done to
      determine eligibility based on clinical laboratory parameters and 10ml of blood will be sent
      to the research laboratory for measurement of erythropoetin, ADMA, MCP-1 and possibly other
      modulators of vascular tone. Girls who are post-menarche will have a urine or serum pregnancy
      test. Prior to the initiation of any study procedures, informed consent and child assent (if
      appropriate) will be obtained from the participant and parents. Immediately prior to the
      initiation of the treatment or placebo phase 24-hour ambulatory blood pressure monitoring
      (ABPM #1) will be performed. Urinary nitrates and protein to creatinine ratio will be
      measured as surrogates for NOS activation and ongoing renal damage. At the end of the
      screening phase, eligible patients will be randomly assigned to either placebo or allopurinol
      for the active phase. Children will receive the other during the crossover phase. The purpose
      of this blinding is to remove either participant or investigator bias from the acquisition of
      the data.

      Active Phase: The active phase will last six weeks and include a clinic visit on the first
      day of the phase, laboratory testing between day 4 and 7, and telephone contact halfway
      through the phase. At the clinic visit, patients will receive their study medication
      (allopurinol or placebo) in a bottle prepared by the investigational pharmacy. Subjects on
      allopurinol will receive 10 mg/kg divided bid (maximum of 400mg). Laboratory tests will be
      performed 4 to 7 days after starting the medication to screen for hepatic or bone marrow
      toxicity (AST, ALT, CBC) and serum uric acid. Evidence for toxicity will cause un-blinding
      and withdrawal from the study. The families will also be instructed to continue the daily
      blood pressure log started in the screening phase. Twenty-four-hour ABPM and end of phase
      laboratory tests including, hemoglobin, serum uric acid, erythropoetin, ADMA, MCP-1 and
      urinary nitrates will be performed at the conclusion of the active phase, prior to
      discontinuing the study medication for the washout phase.

      Washout Phase: Upon completion of the ABPM at the end of the active phase, the study
      medication will be discontinued. The families will continue the home BP logs. The washout
      phase will end when either the child meets criteria for hypertension or two weeks have
      elapsed since completion of the previous phase.

      Crossover Phase: The crossover phase will identical in procedures to the active phase except
      that the medication will be that which was not previously received.

      Follow-up visit: Upon completion of both arms the subjects will have a final clinic visit.
      The laboratory tests will be repeated and if the third ABPM is not complete it will be
      initiated. Conventional antihypertensive therapy will be discussed and initiated if
      appropriate. Routine follow up will be established for management of the child's hypertension
      and other medical problems.
    

Intervention name(s): Allopurinol; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Allopurinol adminsitered one 200mg capsule by mouth twice daily. Placebo capsule once daily during crossover
Intervention MeSH terms: Allopurinol
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment