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Uric Acid in Essential Hypertension in Children

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00288184
First Posted: February 7, 2006
Last Update Posted: September 14, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Baylor University
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  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 Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, 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 ]
  • Casual Blood Pressure [ Time Frame: three months ]

Secondary Outcome Measures:
  • plasma renin activity [ Time Frame: three months ]
  • Systemic vascular resistance [ Time Frame: three months ]

Enrollment: 30
Actual Study Start Date: September 2004
Study Completion Date: August 2007
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Allopurinol
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
Placebo Comparator: Placebo Drug: Placebo

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

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00288184


Locations
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Baylor University
Investigators
Principal Investigator: Daniel I. Feig, MD, PhD Baylor College of Medicine
  More Information

Publications:
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00288184     History of Changes
Other Study ID Numbers: DK64587-DENA (completed)
K23DK064587 ( U.S. NIH Grant/Contract )
First Submitted: February 6, 2006
First Posted: February 7, 2006
Last Update Posted: September 14, 2017
Last Verified: September 2017

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