The purpose of this study is to examine the consequences of lowering serum uric acid in pre-hypertensive, obese adolescents pathways involved with how uric acid mediated hypertension and renal disease. The specific aims are:

1. Test the hypothesis that lowering uric acid will improve endothelial function.

2. Test the hypothesis that lowering uric acid will reduce plasma renin activity and serum angiotensin II levels.

3. Test the hypothesis that lowering uric acid will reduce markers of inflammation

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

The trial will be a double blinded, placebo control trial of two uric acid lowering agents.

The endpoints for this trial will be, endothelial function, systemic vascular resistance, plasma renin activity, MCP-1 and CRP. Upon recruitment and informed consent, children will undergo initial screening. This will include medical history, family history, dietary history, review of systems (questionnaire used and validated in pediatric hypertension clinic) and pediatric quality of life questionnaire. They will have a physical exam, casual and ambulatory blood pressure monitoring (see below) and screening laboratory analysis that will include CBC, electrolytes, BUN, Cr, Uric acid, AST, ALT and urinary micro-albumin to creatinine ratio. Children with serum uric acid less than 5.0mg per dl will be enrolled as controls and only have baseline studies at Screening and Visit 1. Children with serum uric acid equal to or greater than 5.0mg per dl will be randomized (in a one to one to one ratio) to receive placebo, allopurinol or probenecid.

Study drug (or placebo) will be administered for 2 months. During the first week, subjects will take one tablet (placebo, 150mg allopurinol or 250mg probenecid) twice daily. At the end of one week subjects will be instructed to increase to 2 tablets (placebo, 300mg allopurinol or 500mg probenecid) twice daily. Data collection will occur during screening, after one and two months on the study drug and one month after completion of the study drug.

Primary:

• Systemic Vascular Resistance (measured by bioimpedance)
• Brachial Artery Reactivity
• Serum Angiotensin 2
• Serum MCP-1

Secondary:

• Ambulatory BP
• Casual BP
• thromboxane B2
• leptin adiponectin
• IL-6
• endothelin
• PAI-1

Inclusion Criteria:

• Children between the ages of 11 and 18
• body mass index greater than the 95th percentile for age
• Blood pressure between 75th and 95th percentile for age, gender and height percentile

Exclusion Criteria:

• hypertension at the time of screening
• allergy to one of the study medications
• liver function abnormality (AST or ALT greater than twice the upper limit of normal for the laboratory)
• history of renal stones
• renal insufficiency (Schwartz formula calculated GFR less than 70ml per min per 1.73m2
• BSA)
• positive urine pregnancy test
• diabetes
• organ transplant recipient
• currently treated with an angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), diuretic, other medications known to alter serum uric acid level
• lack of ability to comply with the study protocol

Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Texas Children's Hospital

Houston Texas 77030 United States

Overall Clinical Trial Officials and Contacts

Daniel I Feig, MD, PhD Principal Investigator Baylor College of Medicine  

Overall Contact: Daniel I. Feig, MD, PhD 832-824-3800 dfeig@bcm.tmc.edu

Information obtained from ClinicalTrials.gov on July 18, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00288158

Study ID Number: DK71223

ClinicalTrials.gov Identifier: NCT00288158

Health Authority: United States: Federal Government