Unmitigated Aldosterone Signaling During Standard Clinical MRA Dosing

NCT07281014 | Recruiting Phase 4 FDA Drug

• 1 other identifier: 2000040063
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to understand the biology related to the potential shortcomings of existing anti-aldosterone therapy.

Conditions

Heart Failure

Keywords

Spironolactone; Aldosterone

Outcome Measures

Primary Outcomes (1)

• change in urine sodium to potassium ratio

  Change in sodium to potassium ratio between aldosterone vs vehicle infusion during the spironolactone vs. placebo arms.

  59 days

Secondary Outcomes (2)

• Urine Sodium output following saline load

  59 days

• Natriuretic effect of adjuvant to loop diuretic therapy

  59 days

Study Arms (4)

Placebo/placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Placebo/Sprironolactone

ACTIVE COMPARATOR

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.

Drug: Placebo; Drug: Spironolactone 25mg

placebo/aldosterone

ACTIVE COMPARATOR

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.

Drug: Placebo; Drug: Aldosterone

aldosterone/spironolactone

ACTIVE COMPARATOR

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.

Drug: Spironolactone 25mg; Drug: Aldosterone

Interventions

Placebo DRUG

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.

Placebo/Sprironolactone; Placebo/placebo; placebo/aldosterone

Spironolactone 25mg DRUG

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.

Placebo/Sprironolactone; aldosterone/spironolactone

Aldosterone DRUG

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.

aldosterone/spironolactone; placebo/aldosterone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

RECRUITING

MeSH Terms

Conditions

Heart Failure

Interventions

Spironolactone; Aldosterone

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnenediones; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Jeffrey Testani, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Veena Rao

CONTACT

2037857917; veena.s.rao@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2025
• First Posted: December 15, 2025
• Study Start: January 27, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)