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Mechanism and Effects of Manipulating Chloride Homeostasis in Stable Heart Failure

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ClinicalTrials.gov Identifier: NCT03440970
Recruitment Status : Recruiting
First Posted : February 22, 2018
Last Update Posted : September 30, 2022
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Yale University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Decompensated Heart Failure Drug: Lysine Chloride Other: Placebo Early Phase 1

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Mechanism and Effects of Manipulating Chloride Homeostasis in Stable Heart Failure
Actual Study Start Date : January 15, 2019
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Experimental: Lysine Chloride
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.
Drug: Lysine Chloride
Patients will receive the study drug twice a day for 5 days.

Placebo Comparator: Placebo
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.
Other: Placebo
Patients will receive the placebo twice a day for 5 days.




Primary Outcome Measures :
  1. Change in Blood Volume [ Time Frame: Daily for 7-days ]
    Volumex is albumin labeled with the iodine isotope I-131 and is an FDA-approved method used to determine total blood volume. A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of blood collection will be compared across the 7 day collection period between intervention and placebo arms.


Secondary Outcome Measures :
  1. Change in log NTpro-BNP [ Time Frame: Daily for 7-days ]
    N-terminal prohormone of brain natriuretic peptide (NTpro-BNP) is used to screen and diagnosis of acute congestive heart failure (CHF) and can be used to establish prognosis in heart failure. A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of NTpro-BNP will be compared across the 7 day collection period between intervention and placebo arms.

  2. Change in Serum Creatinine [ Time Frame: Daily for 7-days ]
    A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of serum creatinine will be compared across the 7 day collection period between intervention and placebo arms.

  3. Change in Cystatin C [ Time Frame: Daily for 7-days ]
    A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of cystatin C will be compared across the 7 day collection period between intervention and placebo arms.

  4. Change in Chloride [ Time Frame: Daily for 7-days ]
    A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of chloride will be compared across the 7 day collection period between intervention and placebo arms.

  5. Change in Bicarbonate [ Time Frame: Daily for 7-days ]
    A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of bicarbonate will be compared across the 7 day collection period between intervention and placebo arms.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Meticulous history of medical compliance and attendance of appointments
  • Stable heart failure as defined by:

    1. Absence of hospitalizations for 90 days
    2. Stable diuretic and medical therapy for 30 days
    3. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03440970


Contacts
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Contact: Katherine Keith 8602273925 katherine.keith@yale.edu
Contact: Jeffrey M Testani 2037376227 jeffrey.testani@yale.edu

Locations
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United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06510
Contact: Jeffrey Testani, MD       jeffrey.testani@yale.edu   
Sponsors and Collaborators
Yale University
National Heart, Lung, and Blood Institute (NHLBI)
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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT03440970    
Other Study ID Numbers: 2000022016
1R01HL139629-01 ( U.S. NIH Grant/Contract )
First Posted: February 22, 2018    Key Record Dates
Last Update Posted: September 30, 2022
Last Verified: September 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Yale University:
Chloride homeostasisH
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases