Evaluating Hormonal Mechanisms for Vitamin D Receptor Agonist Therapy in Diabetes: The VALIDATE-D Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- The Change in Circulating RAS Activity After Calcitriol/Placebo Therapy
研究概览
简要总结
The purpose of this study is to evaluate whether vitamin D receptor agonist therapy lowers renin-angiotensin system activity.
详细描述
This study aims to evaluate whether vitamin D receptor agonist therapy (calcitriol) in diabetes lowers renin-angiotensin system (RAS) activity in a manner similar to an ACE inhibitor. This is a physiology study, focused on evaluating hormonal changes in the circulating and tissue RAS when compared to placebo.
Subjects with type 2 diabetes and obesity and normal kidney function will undergo evaluation of their circulating and renal-vascular RAS activity and urinary protein at baseline, after withdrawing interfering medications, while on a controlled electrolyte diet, and in controlled posture settings. They will then randomly receive a study medication (calcitriol or placebo) for 3 weeks followed by a re-assessment of their RAS parameters. The main outcomes that will be evaluated following calcitriol/placebo include measures of the circulating renin activity (primary), as well as measures of the renal-vascular RAS (renal plasma flow) and urine protein (secondary)
The primary outcome is the change in the plasma renin activity when sodium restricted, before and after intervention. Secondary outcomes include the change in renal plasma flow and urine protein when sodium loaded, before and after intervention.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type-Two Diabetes (treated with diet alone, with oral hypoglycemic agents, or with a single injection of basal insulin daily)
- •Normal blood pressure, or Mild (Stage 1) Hypertension that is either untreated, or adequately treated with a single anti-hypertensive drug.
- •Age >18 years and <70 years
- •Estimated GFR > 60ml/min
- •Normal laboratory values for: Complete blood count, sodium, potassium, glucose, liver enzymes, urinalysis
- •Electrocardiogram without any signs of prior infarction, ventricular conduction abnormality, or supraventricular arrhythmia.
排除标准
- •Chronic Kidney Disease or eGFR<60
- •History of nephrolithiasis (kidney stones)
- •Multiple (more than one) insulin injections daily (since insulin can alter the RAS)
- •Poorly controlled type 2 diabetes (That may require more aggressive therapy) as defined by an HbA1c>8.5%
- •Type 1 diabetes
- •Stage 2 or Stage 3 hypertension or the use of more than 1 antihypertensive drug
- •Chronic inflammatory conditions (such as inflammatory bowel disease or arthritis) that are treated with prescribed doses of NSAIDs by a physician.
- •The use of prescribed doses of potassium supplements.
- •History of liver failure
- •History of parathyroid or granulomatous disorders
- •History of heart failure, cerebrovascular disease or coronary heart disease
- •History of known microvascular complications of diabetes (including retinopathy, neuropathy, nephropathy)
- •Illness requiring overnight hospitalization in the past 6 months
- •Active tobacco or recreational drug use
- •Pregnancy or current breast feeding
研究组 & 干预措施
calcitriol
Subjects will receive calcitriol (titrated up to 0.75 mcg daily) for 3 weeks.
干预措施: Calcitriol (Drug)
placebo
Subjects will receive placebo for 3 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
The Change in Circulating RAS Activity After Calcitriol/Placebo Therapy
时间窗: baseline and 2 weeks following calcitriol/placebo therapy
The below results represent the change in Plasma Renin Activity.
次要结局
- Change in Renal Plasma Flow After Calcitriol/Placebo Therapy(baseline and 3 weeks following calcitriol/placebo therapy)
- Change in Urine Protein After Calcitriol/Placebo Therapy(baseline and 3 weeks following calcitriol/placebo therapy)
研究者
Anand Vaidya
Assistant Professor of Medicine, Harvard Medical School
Brigham and Women's Hospital