Effect of Alkali Therapy on Vascular and Graft Function in Kidney Transplant
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Change in Brachial artery flow mediated dilation at 12 months
研究概览
简要总结
Lower serum bicarbonate levels, even within the normal laboratory range, in kidney transplant recipients (KTRs) are associated with an increased risk of graft loss, cardiovascular events and mortality. Because acid retention is common in KTRs, it is plausible that alkali therapy in KTRs may also result in improved vascular and graft function. The investigators will perform a randomized, double-blinded, placebo-controlled, 12 month study in 120 KTRs to examine the effect of sodium bicarbonate therapy on surrogate markers of CVD and graft function. The overall hypothesis is that treatment with bicarbonate will improve indicators of vascular and graft function in KTRs by decreasing complement activation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-80 years
- •Serum bicarbonate 16-24 mEq/L on 2 separate measurements (at least 1 day apart)
- •Kidney transplant received 1 year prior to randomization
- •eGFR ≥ 45 ml/min/1.73m2 by CKD-EPI equation
- •Blood pressure <130/80 mm Hg prior to randomization
- •BMI < 40 kg/m2 (FMD measurements can be inaccurate in severely obese patients).
- •Able to provide consent
- •Immunosuppression regimen consisting of tacrolimus, mycophenolate mofetil and prednisone (95% of patients at University of Colorado are on this regimen)
- •Stable immunosuppression regimen for at least three months prior to randomization
- •Stable anti-hypertensive regimen for at least one month prior to randomization
- •Not taking medications that interact with agents administered during experimental sessions (e.g. sildenafil interacts with nitroglycerin).
排除标准
- •Significant comorbid conditions that lead the investigator to conclude that life expectancy is less than 1 year
- •Use of chronic daily oral alkali within the last 3 months (including sodium bicarbonate, calcium carbonate or baking soda)
- •Uncontrolled hypertension
- •Serum potassium < 3.3 or ≥ 5.5 mEq/L at screening
- •New York Heart Association Class 3 or 4 heart failure symptoms, known EF ≤30%, or hospital admission for heart failure within the past 3 months
- •Nephrotic range proteinuria (urine complement activation fragment measurements may not be accurate with severe proteinuria)
- •Factors judged to limit adherence to interventions
- •Current participation in another research study
- •Pregnancy or planning to become pregnant or currently breastfeeding
- •Chronic use of supplemental oxygen
- •Use of anticoagulants
研究组 & 干预措施
Sodium bicarbonate
Oral sodium bicarbonate at a dose of 0.5 mEq/kg-lean body weight/day
干预措施: Sodium bicarbonate (Drug)
Placebo
Oral placebo at a dose of 0.5 mEq/kg-lean body weight/day
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Brachial artery flow mediated dilation at 12 months
时间窗: Baseline and 12 months
Brachial artery FMD will be determined using high-resolution ultrasonographyECG-gated end-diastolic ultrasound images and Doppler flow of the brachial artery will be acquired during baseline and FMD conditions. For FMD, reactive hyperemia will be produced by inflating a pediatric BP cuff around the forearm to 250 mmHg for 5 minutes followed by rapid deflation.
次要结局
- Change in Large elastic artery stiffness and compliance at 12 months(Baseline and 12 months)
- Change in Tubular atrophy at 12 months(Baseline and 12 months)
- Change in interstitial fibrosis at 12 months(Baseline and 12 months.)
- Change in participant plasma and urine complement activation fragment levels at 12 months(Baseline and 12 months)