Mechanism and Effects of Manipulating Chloride Homeostasis in Stable Heart Failure

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Yale University

Status and phase

Enrolling
Early Phase 1

Conditions

Decompensated Heart Failure

Treatments

Drug: Lysine Chloride
Other: Placebo

Study type

Interventional

Funder types

Other
NIH

Identifiers

NCT03440970
2000022016
1R01HL139629-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This study is designed to investigate the quantitative effects of sodium-free chloride supplementation on electrolyte balance, volume status, and sodium avidity in stable heart failure patients in a highly controlled environment.

Full description

The overarching goal of this study 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). This study is designed as a highly controlled inpatient "GCRC" arm to be compared to a real world efficacy study that has been proposed as a separate study. With extensive biobanking and analysis of samples in the inpatient setting, we will be able to deliver a great wealth of information on the biology and therapeutic potential of manipulating chloride homeostasis in heart failure.

Enrollment

20 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Meticulous history of medical compliance and attendance of appointments

Stable heart failure as defined by:

  • Absence of hospitalizations for 90 days
  • Stable diuretic and medical therapy for 30 days
  • Opinion of the patient's treating physician (Heart Failure Cardiologist) that the patient is at optimal volume status
  • Evidence based heart failure treatment with maximally-tolerated doses of a beta blocker, ACE/ARB/neprilysin inhibitor and aldosterone antagonist
  • Ejection fraction <40%
  • Chronic loop diuretic therapy with ≥ 40 mg of furosemide equivalents
  • Serum chloride <102 mmol/L

Exclusion criteria

  • Inability to commit to or comply with the rigorous outpatient or inpatient study protocol
  • Use of a thiazide diuretic in the last 30 days
  • History of metabolic or respiratory acidosis
  • 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 safely discontinued for the inpatient randomized periods in each arm. Any participants who have consistently elevated Blood glucose readings > 200 mg/dL while inpatient will not be enrolled.
  • Serum bicarbonate level <24mmol/L
  • Estimated glomerular filtration rate <30 mL/min or prior or current history of renal replacement therapy
  • Anemia, as defined by Hemoglobin <8.0 g/dL at screening visit
  • Urinary incontinence or significant bladder dysfunction (post-void residual at screening >100 mL
  • Use of chloride containing medications that provide more than 5 mmol/day of chloride if the medication cannot be discontinued or substituted
  • Appears unlikely, or unable to participate in the required study procedures, as assessed by the study PI or research RN (ex: clinically-significant psychiatric, addictive, or neurological disease)
  • Inability to give written informed consent or follow study protocol

Trial design

Primary purpose

Diagnostic

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Triple Blind

20 participants in 2 patient groups, including a placebo group

Lysine Chloride
Experimental group
Description:
Patients will be randomized to receive either lysine chloride or placebo. Patients will receive the study drug twice a day for 5 days of randomized therapy, starting after the completion of a blood volume assessment.
Treatment:
Drug: Lysine Chloride
Placebo
Placebo Comparator group
Description:
Patients will be randomized to receive either lysine chloride or placebo. Patients will receive the study drug twice a day for 5 days of randomized therapy, starting after the completion of a blood volume assessment.
Treatment:
Other: Placebo

Trial contacts and locations

1

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Central trial contact

Jeffrey M Testani; Katherine Keith

Data sourced from clinicaltrials.gov

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