Mechanism and Effects of Manipulating Chloride Homeostasis in Acute Heart Failure

NCT ID: NCT03446651

Last Updated: 2024-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-12
• Study Completion Date: 2022-09-07

Brief Summary

The purpose of this study is to understand the effects of chloride supplementation on volume-overloaded acute heart failure patients concomitantly treated with IV diuretics.

Detailed Description

The overarching goal of this proposal is to develop a comprehensive understanding of the biology and therapeutic potential of sodium-free chloride supplementation. While sodium homeostasis has been the focus of substantial investigation, very little research has been devoted to understanding chloride homeostasis. Thus, this proposal is designed to obtain the full spectrum of information pertaining to chloride, such as novel areas with great interest by the scientific community (i.e. modulation of the WNK-kinase system and the use of exosomes), to more practical/basic questions (i.e. what happens to sodium chloride balance when a patient is challenged with chloride). The proposed outpatient study has been designed to serve as a real world efficacy study. With extensive biobanking and analysis of samples in the proposed setting, there is the potential to be able to deliver a great wealth of information on the biology and therapeutic potential of manipulating chloride homeostasis in heart failure.

Research confirms that many heart failure therapies demonstrate measurable benefit in highly controlled environments, but lack effectiveness when studied in decompensated patients receiving standard decongestive therapies. As such, this study seeks to understand the effects of chloride supplementation on volume-overloaded patients concomitantly treated with IV diuretics.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: TRIPLE

Study Groups

Lysine Chloride

Participants will be randomized to 7 days of therapy with either 115 mmol/day of lysine chloride or placebo. People in the Lysine Chloride group will receive the active intervention.

Group Type: EXPERIMENTAL

Lysine Chloride

Intervention Type: DRUG

Patients will receive 7 days of therapy using 115 mmol/day of lysine chloride. Patients will be given the option of a taste test of both lysine chloride \& the placebo powders mixed with various beverages to ensure it is palatable to them. If the patient feels they will not be able to take the study medication twice a day due to taste, they will be withdrawn from the study at this time.

Placebo

Participants will be randomized to 7 days of therapy with either 115 mmol/day of lysine chloride or placebo. People in the Placebo group will receive placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Patients will receive 7 days of therapy using placebo. Patients will be given the option of a taste test of both lysine chloride \& the placebo powders mixed with various beverages to ensure it is palatable to them. If the patient feels they will not be able to take the study medication twice a day due to taste, they will be withdrawn from the study at this time.

Interventions

Lysine Chloride

Patients will receive 7 days of therapy using 115 mmol/day of lysine chloride. Patients will be given the option of a taste test of both lysine chloride \& the placebo powders mixed with various beverages to ensure it is palatable to them. If the patient feels they will not be able to take the study medication twice a day due to taste, they will be withdrawn from the study at this time.

Intervention Type: DRUG

Placebo

Patients will receive 7 days of therapy using placebo. Patients will be given the option of a taste test of both lysine chloride \& the placebo powders mixed with various beverages to ensure it is palatable to them. If the patient feels they will not be able to take the study medication twice a day due to taste, they will be withdrawn from the study at this time.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Clinical diagnosis of decompensated heart failure with at least one objective sign of volume overload (rales, edema, elevated jugular venous pressure (JVP), or weight gain of at least 5 pounds)
• A projected need by the treating clinician for continued treatment with IV diuretics
• Chronic loop diuretic use

Exclusion Criteria

• Inability to commit to or comply with serial visits for treatment in the Yale Transitional Care Center (YTCC)
• History of severe metabolic or respiratory acidosis within 30 days of enrollment
• Use of metformin, acetazolamide, or any other agent that could predispose to acidosis. Patients who are on metformin may be enrolled if their metformin can be discontinued safely for the duration of the study. Any participants who have consistently elevated Blood glucose readings > 200 mg/dL while inpatient will not be enrolled.
• Serum bicarbonate level <20mmol/L
• Estimated glomerular filtration rate <20 mL/min or renal replacement therapy
• Appears unlikely, or unable to participate in the required study procedures, as assessed by the study PI or research registered nurse (RN) (ex: clinically-significant psychiatric, addictive, or neurological disease)
• Inability to give written informed consent or follow study protocol

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

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Yale University

New Haven, Connecticut, United States

Countries

United States

References

Kazory A. Combination Diuretic Therapy to Counter Renal Sodium Avidity in Acute Heart Failure: Trials and Tribulations. Clin J Am Soc Nephrol. 2023 Oct 1;18(10):1372-1381. doi: 10.2215/CJN.0000000000000188. Epub 2023 Apr 27.

Reference Type: DERIVED

PMID: 37102974 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1R01HL139629-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000022001

Identifier Type: -

Identifier Source: org_study_id