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Uric Acid in Essential Hypertension in Children

This study has been completed.
Sponsor:
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00288184
First received: February 6, 2006
Last updated: January 12, 2010
Last verified: January 2010
  Purpose

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


Condition Intervention Phase
Essential Hypertension
Drug: Allopurinol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Double-blinded, Placebo-controlled, Cross-over Trial of Allopurinol for the Treatment of Newly Diagnosed Essential Hypertension in Adolescents

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Ambulatory BP [ Time Frame: three months ] [ Designated as safety issue: No ]
  • Casual Blood Pressure [ Time Frame: three months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • plasma renin activity [ Time Frame: three months ] [ Designated as safety issue: No ]
  • Systemic vascular resistance [ Time Frame: three months ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: December 2003
Study Completion Date: August 2007
Arms Assigned Interventions
Active Comparator: A
Hypertensive children received both placebo and allopurinol in a cross over design.
Drug: Allopurinol
Allopurinol adminsitered one 200mg capsule by mouth twice daily. Placebo capsule once daily during crossover

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.

  Eligibility

Ages Eligible for Study:   12 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Males or females 12 to 18 years in age.

SBP or DBP greater than 95th percentile for age, gender and height

Diagnosis of primary hypertension after initial workup

No pharmacological therapy for hypertension in the past 12 months

Females must have a negative urine pregnancy test.

Parental or guardian consent and child subject assent

Exclusion Criteria:

Severe or poorly controlled hypertension as defined by SBP or DBP more than 20mmHg >95th percentile for age, gender and height or a history of hypertensive encephalopathy

Identified cause of secondary hypertension Renal transplant

Taking a calcineurin inhibitor, azathioprine or another nucleoside analogue medication (These medications have potentially serious drug interactions with Allopurinol.)

Currently receiving antihypertensive medication(s) or diuretic(s)

Laboratory abnormalities that indicate clinically significant hematologic, hepatobiliary or renal disease (These abnormalities would be expected to alter drug metabolism and increase the likelihood of medication side effects.):

Schwartz Formula GFR less than 60ml/min/1.73m2, AST/SGOT greater than 2 times the upper limit of normal* ALT/SGPT greater than 2 times the upper limit of normal* Total or direct bilirubin more than 2 times the upper limit of normal* Hemoglobin less than 9 gm/dl WBC less than 3.000/mm3 Platelet count less than 100,000/mm3 *age-adjusted normal range

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00288184

Locations
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Daniel I. Feig, MD, PhD Baylor College of Medicine
  More Information

No publications provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Daniel I. Feig, MD, PhD, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00288184     History of Changes
Other Study ID Numbers: DK64587-DENA (completed), 5 K23 DK064587
Study First Received: February 6, 2006
Last Updated: January 12, 2010
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases
Allopurinol
Antimetabolites
Antioxidants
Antirheumatic Agents
Enzyme Inhibitors
Free Radical Scavengers
Gout Suppressants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014