Unmitigated Aldosterone Signaling During Standard Clinical MRA Dosing
Yale University
Summary
The purpose of this research study is to understand the biology related to the potential shortcomings of existing anti-aldosterone therapy.
Description
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 spironolac…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Chronic stable heart failure at optimal volume status. Inclusion will require participants to be NYHA class I or II. 2. eGFR \> 30 ml/min/1.73m2 3. Serum potassium ≤5.0 meq/L and ≥3.5 meq/L 4. Stable heart failure medications without need or expectation for changes during the 8-week study period 5. Free from heart failure decompensation for the preceding 60 day 6. 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. Exclusion Criteria: 1. Unc…
Interventions
- DrugPlacebo
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.
- DrugSpironolactone 25mg
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.
- DrugAldosterone
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.
Location
- Yale UniversityNew Haven, Connecticut