Study of Aldosterone Signaling and Low Dose Spironolactone in Heart Failure Using Intravenous Aldosterone and Oral Treatments

What this Trial Is About

Researchers are studying the biology behind why current anti-aldosterone treatments may not work fully in people with chronic stable heart failure classified as NYHA class I or II. This Phase 4 trial aims to better understand aldosterone signaling during standard low-dose mineralocorticoid receptor antagonist (MRA) therapy and its potential shortcomings. The study focuses on how aldosterone affects the body's sodium and potassium balance using a controlled experimental approach. Participants will take part in a randomized, double-blind, placebo-controlled crossover study where they receive four different treatments in random order: intravenous (IV) infusion of either aldosterone or a vehicle (placebo), combined with oral doses of either 25 mg spironolactone or a placebo pill. Each treatment period lasts up to 59 days with two-week breaks between periods to ensure drug levels stabilize or wash out. The study tests the effects of these combinations on urine sodium to potassium ratios and sodium output following a salt challenge. During the study, participants will undergo evaluations including urine tests to measure sodium and potassium changes. Researchers will collect biospecimens needed to test their hypotheses about aldosterone signaling during treatment. Safety monitoring will include blood pressure and kidney function checks. The total study duration per participant includes multiple treatment phases separated by washout periods, lasting about eight weeks in total.

Unmitigated Aldosterone Signaling During Standard Clinical MRA Dosing