Primary Prevention of Hypertension in Obese Adolescents
Summary
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
Description
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.
Study Design
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Conditions
Obesity
Intervention
Allopurinol vs. Probenecid vs. Placebo
Location
Texas Children's Hospital
Houston
Texas
United States
77030
Status
Completed
Source
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00288158
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Probenecid
The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy.
Obesity, Abdominal
A condition of having excess fat in the abdomen. Abdominal obesity is typically defined as waist circumferences of 40 inches or more in men and 35 inches or more in women. Abdominal obesity raises the risk of developing disorders, such as diabetes, hypertension and METABOLIC SYNDROME X.
Allopurinol
A XANTHINE OXIDASE inhibitor that decreases URIC ACID production. It also acts as an antimetabolite on some simpler organisms.
Obesity, Morbid
The condition of weighing two, three, or more times the ideal weight, so called because it is associated with many serious and life-threatening disorders. In the BODY MASS INDEX, morbid obesity is defined as having a BMI greater than 40.0 kg/m2.
Therapeutic Misconception
Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.
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