University of Alabama at Birmingham CORT Project 2: The Effects of Urate Lowing Therapy (ULT) in Inflammation, Endothelial Function, and Blood Pressure
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 99
- 试验地点
- 1
- 主要终点
- Change in Flow-mediated Arterial Vasodilation
研究概览
简要总结
We propose a novel intervention for reducing BP that could have a preferential impact in patients with hyperuricemia and gout. There is a great need for new anti-hypertensives, particularly among those with gout. The proposed study is novel in its plans to investigate the physiologic mechanisms through which urate contributes to vascular disease and by which ULT may contribute to BP reduction. Also innovative, we will: 1) determine to what extent the described benefit of lowering serum urate extends beyond the adolescent population previously studied into young adults, 2) test whether a urate-lowering approach will benefit individuals that do not yet meet the current definition of hyperuricemia and do not have gout, and 3) begin to explore potential mechanisms for the higher prevalence of hypertension among African-Americans. If successful, this work could translate to the standard of clinical care and to health care recommendations for the population as a whole.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Pre-hypertension or stage I hypertension, defined as the following after the mean of two clinic measurements:
- •Systolic blood pressure (SBP) ≥ 120 and <160 or;
- •Diastolic blood pressure (DBP) ≥ 80 and < 100
- •Serum urate ≥ 5.0 mg/dL for men or ≥ 4.0 mg/dL for women
- •Age 18-40
排除标准
- •Any current pharmacological treatment for hypertension, including diuretics (calcium channel blockers at stable doses were later allowed)
- •Estimated glomerular filtration rate < 60 mL/min/1.73m2
- •Current use of any urate-lowering therapy or statins
- •Prior diagnosis of gout or past use of urate-lowering therapy for gout
- •Prior diagnosis of diabetes
- •Pregnancy, or recent delivery or last trimester pregnancy loss more recent than 3 months
- •Active smokers
- •Immune-suppressed individuals including transplant recipients or current use of azathioprine.
- •Leucopenia with absolute white cell count < 3000 /mL, anemia with hemoglobin < 12 g/dL, or thrombocytopenia with platelet count < 150,000/mL
- •Individuals of Han Chinese or Thai descent with HLAB5801 genetic phenotype
- •Serious medical condition that at investigator's judgment precludes utilization of a fixed dose of allopurinol
研究组 & 干预措施
Allopurinol, Then Placebo
Participants will be asked to take 4 weeks of allopurinol (300 mg oral per day), then will crossover (after 2-4 week washout period) and take placebo for an additional 4 weeks.
干预措施: Allopurinol (Drug)
Allopurinol, Then Placebo
Participants will be asked to take 4 weeks of allopurinol (300 mg oral per day), then will crossover (after 2-4 week washout period) and take placebo for an additional 4 weeks.
干预措施: Placebo (Drug)
Placebo, Then Allopurinol
Participants will be asked to take 4 weeks of placebo, then will crossover (after 2-4 week washout period) and take allopurinol (300 mg oral per day) for an additional 4 weeks.
干预措施: Allopurinol (Drug)
Placebo, Then Allopurinol
Participants will be asked to take 4 weeks of placebo, then will crossover (after 2-4 week washout period) and take allopurinol (300 mg oral per day) for an additional 4 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Flow-mediated Arterial Vasodilation
时间窗: 4 weeks (pre-treatment vs. post-treatment FMD Values (%))
Compare endothelial function as indexed by flow-mediated arterial vasodilation (FMD) within each phase of treatment (allopurinol 300 mg/day PO or placebo). Percent (%) change in FMD is calculated by comparing FMD (%) at the end of each treatment phase to pre-treatment values.
Change in Systolic Blood Pressure (SBP)
时间窗: 4 weeks (pre-treatment vs. post-treatment SBP)
Compare systolic blood pressure (SBP) captured by wearing a 24 hour ambulatory blood pressure monitor during each phase of treatment (allopurinol 300 mg/day PO or placebo). Change in systolic blood pressure is calculated by comparing SBP at the end of each treatment phase to pre-treatment values.
Change in Serum Levels of High Sensitivity C-reactive Protein
时间窗: 4 weeks (pre-treatment vs. post-treatment serum levels)
Serum level of high sensitivity C-reactive protein will be reported as a change during treatment phase (allopurinol 300 mg/day PO or placebo). Change in serum level of C-reactive protein is calculated by comparing serum values at the end of each treatment phase to pre-treatment levels.
次要结局
未报告次要终点
研究者
Kenneth Saag, MD, MSc
Professor of Medicine
University of Alabama at Birmingham