Unmitigated Aldosterone Signaling During Standard Clinical MRA Dosing
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- change in urine sodium to potassium ratio
研究概览
简要总结
The purpose of this research study is to understand the biology related to the potential shortcomings of existing anti-aldosterone therapy.
详细描述
This is a randomized, double blind, double dummy, placebo-controlled, crossover study where aldosterone will be infused intravenously (IV) with and without guideline recommended low dose oral mineralocorticoid receptor antagonists therapy. Participants will receive, in a randomized order, 1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone. Each crossover period will be separated by 2 weeks to allow for steady state blood level of spironolactone and metabolites to be reached (or complete washout from prior spironolactone). The broad study design will be designed around evaluation of change in urine sodium to potassium ratio, sodium output following a sodium chloride challenge, and collecting the necessary biospecimens to test our hypotheses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic stable heart failure at optimal volume status. Inclusion will require participants to be NYHA class I or II.
- •eGFR > 30 ml/min/1.73m2
- •Serum potassium ≤5.0 meq/L and ≥3.5 meq/L
- •Stable heart failure medications without need or expectation for changes during the 8-week study period
- •Free from heart failure decompensation for the preceding 60 day
- •Systolic blood pressure >90 mmHg if not taking an MRA at screening. If patients are already taking an MRA at the time of screening a systolic blood pressure needs to be >80 mmHg.
排除标准
- •Uncontrolled hypertension (SBP > 160 mmHg)
- •Severe bladder dysfunction
- •Current MRA dose > 50mg spironolactone or equivalent or non MRA potassium sparing diuretic such as amiloride
- •Contraindication to initiation or withdrawal of spironolactone per study procedures
- •History of severe hyperkalemia (K>6.0 meq/l)
- •Brittle volume sensitive heart failure, recurrent flash pulmonary edema, restrictive cardiomyopathy or other pathology that would make aldosterone infusion high risk
- •Pregnant or breastfeeding
- •Women of childbearing potential that are not receiving a highly effective form of contraception. Females of childbearing potential must agree to use a highly effective method of birth control until 14 days after the last dose of study drug. The following are highly effective methods for this study:
- •Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
- •Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable
- •Intrauterine device (IUD)
- •Intrauterine hormone-releasing system (IUS)
- •Bilateral tubal occlusion
- •Vasectomized partner
- •Sexual abstinence
研究组 & 干预措施
Placebo/placebo
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations
1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59.
干预措施: Placebo (Drug)
Placebo/Sprironolactone
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations
1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59.
干预措施: Placebo (Drug)
Placebo/Sprironolactone
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations
1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59.
干预措施: Spironolactone 25mg (Drug)
placebo/aldosterone
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations
1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59.
干预措施: Placebo (Drug)
placebo/aldosterone
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations
1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59.
干预措施: Aldosterone (Drug)
aldosterone/spironolactone
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations
1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59.
干预措施: Spironolactone 25mg (Drug)
aldosterone/spironolactone
This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations
1) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59.
干预措施: Aldosterone (Drug)
结局指标
主要结局
change in urine sodium to potassium ratio
时间窗: 59 days
Change in sodium to potassium ratio between aldosterone vs vehicle infusion during the spironolactone vs. placebo arms.
次要结局
- Urine Sodium output following saline load(59 days)
- Natriuretic effect of adjuvant to loop diuretic therapy(59 days)