Unmitigated Aldosterone Signaling During Standard Clinical MRA Dosing

NCT ID: NCT07281014

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2027-08-31

Brief Summary

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

Detailed 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 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.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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

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.

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: 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.

Spironolactone 25mg

Intervention Type: 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/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.

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: 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

Intervention Type: 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

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.

Group Type: ACTIVE_COMPARATOR

Spironolactone 25mg

Intervention Type: 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

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Spironolactone 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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

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. Uncontrolled hypertension (SBP > 160 mmHg)

2. Severe bladder dysfunction

3. Current MRA dose > 50mg spironolactone or equivalent or non MRA potassium sparing diuretic such as amiloride

4. Contraindication to initiation or withdrawal of spironolactone per study procedures

5. History of severe hyperkalemia (K>6.0 meq/l)

6. Brittle volume sensitive heart failure, recurrent flash pulmonary edema, restrictive cardiomyopathy or other pathology that would make aldosterone infusion high risk

7. Pregnant or breastfeeding

8. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Testani, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale University

New Haven, Connecticut, United States

Countries

United States

Central Contacts

Veena Rao

Role: CONTACT

veena.s.rao@yale.edu

2037857917

Other Identifiers

2000040063

Identifier Type: -

Identifier Source: org_study_id