Allopurinol for Renal Transplant Associated Hypertension in Children

This study has been terminated.
(insufficient number of eligible subjects)
Sponsor:
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00288171
First received: February 6, 2006
Last updated: June 6, 2011
Last verified: June 2011
  Purpose

To test the hypothesis that lowering serum uric acid will ameliorate hypertension in children after renal transplantation.


Condition Intervention Phase
Hypertension
Renal Transplant
Drug: placebo
Drug: Allopurinol and placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/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 Post-renal-transplant Hypertension in Children

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Systolic Blood Pressure [ Time Frame: 2 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Serum Creatinine [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • urinary bradykinin [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • urinary nitrates [ Time Frame: 2 months ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: February 2006
Study Completion Date: June 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A hypertension
Hypertensive renal transplant recipients with elevated uric acid will the treated with allopurinol and placebo in an randomized cross over fashion. Subjects will serve as their own controls.
Drug: placebo
placebo capsule twice daily for one month
Drug: Allopurinol and placebo
Allopurinol 200mg twice daily for one month

Detailed Description:

The study will be a double-blind, placebo-controlled, crossover trial. We will recruit 25 children between the ages of 6 and 18 years, from the pediatric renal transplant program at Texas Children's Hospital. The study consists of three phases, a screening phase, and a treatment phase, and a crossover phase.

Clinical study design: The study will be a double-blind, placebo-controlled, crossover trial. We will recruit 25 children between the ages of 6 and 18 years, from the pediatric renal transplant program at Texas Children's Hospital. The study consists of three phases, a screening phase, and a treatment phase, and a crossover phase.

Laboratory Measurements: The laboratory measurements will be performed in the CLIA approved, clinical laboratory at Texas Children's Hospital.

Definition of high blood pressure: We will use the guidelines for blood pressure measurement that have been adapted from the Update on the Task Force Report (1987) on High Blood Pressure in Children and Adolescents [22]. Hypertension will be defined as >95th percentile blood pressure for age, height percentile (rounded to the nearest of 5th, 10th, 25th, 50th, 75th, 90th, or 95th percentile of height above the patients actual height) and gender. Each blood pressure measurement will be the mean of 3 right arm readings, taken with an mercury sphygmomanometer at least three minutes apart with the patient sitting upright and relaxed. For the purposes of the study, to be defined as hypertensive, a patient will need to have mean systolic or diastolic blood pressure >95th percentile on three consecutive occasions, on separate days over at least a 1 week period. Patients with previously confirmed hypertension will be reconfirmed during the screening period.

Screening phase: The screening phase will last between 1 and 2 weeks. Patients will be taught to use 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. Blood tests will be done to determine eligibility based on clinical laboratory parameters. Girls who are post-menarche will have a urine pregnancy test. Each child will undergo 24hr ambulatory blood pressure monitoring during the screening phase. Children will collect urine for 24-hours for the purpose of screening urinary nitrates and bradykinin.

Phase 1: 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 weekly telephone contact throughout the phase. Subjects will receive allopurinol or placebo. Laboratory tests will be performed 4 to 7 days after starting the medication to screen for hepatic or bone marrow toxicity (AST, ALT, CBC), renal function (Cr), cyclosporin or tacrolimus level and serum uric acid. Evidence for toxicity, increased creatinine or unstable cyclosporin levels will lead to immediate discontinuation of allopurinol withdrawal from the study. The families will also be instructed to continue the daily blood pressure log started in the screening phase. At the end of the phase, prior to discontinuation of the allopurinol, children will again undergo 24hr ambulatory blood pressure monitoring. Children will repeat the 24-hour urine collection for the purpose of screening urinary nitrates and bradykinin.

Washout Phase: There will be a two-week washout interval between the allopurinol and placebo phases.

Crossover Phase: The crossover phase will identical in procedures to the active phase except that the children will be receiving allopurinol or placebo, whichever was not received in Phase 1.

  Eligibility

Ages Eligible for Study:   6 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Males or females 6 to 18 years in age. Post-menarche females must have a negative urine pregnancy test.

Renal transplant recipient taking cyclosporin.

Weight greater than 20kg

Parental or guardian consent and child subject assent (if appropriate)

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

Exclusion Criteria:

Severe or poorly controlled hypertension as defined by SBP or DBP more than 20mmHg >95th percentile for age, gender and height on active therapy, on 2 or more antihypertensive medications or a history of hypertensive encephalopathy

Taking azathioprine or another nucleoside analogue medication

Currently receiving ACE-I or ARB medications

Laboratory abnormalities that indicate clinically significant hematologic, hepatobiliary or renal disease: Schwartz Formula GFR less than 60ml/min/1.73m2 ALT/SGPT greater 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, TCH laboratory

A history of cardiomyopathy, clinically significant structural heart disease or atrioventricular conduction disturbance, sick sinus syndrome, clinically significant cardiac arrhythmia or symptoms of congestive heart failure

Pregnant or lactating females

Any other investigational drug use within 30 days of enrollment

Parents/guardians or subjects who, in the opinion of the investigator, may be non-compliant with the study procedures.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00288171

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

Responsible Party: Daniel I. Feig, MD, Principle Investigator, Baylor College Medicine
ClinicalTrials.gov Identifier: NCT00288171     History of Changes
Other Study ID Numbers: DK64587-POST (terminated)
Study First Received: February 6, 2006
Last Updated: June 6, 2011
Health Authority: United States: Federal Government

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

ClinicalTrials.gov processed this record on April 23, 2014