Mechanism and Effects of Manipulating Chloride Homeostasis in Stable Heart Failure

NCT03440970 | Completed Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: 20000220161R01HL139629-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Decompensated Heart Failure

Keywords

Chloride homeostasisH

Outcome Measures

Primary Outcomes (2)

• Mean Change in Blood Volume

  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. Day 1 and day 7 measures of blood collection will be compared between intervention and placebo arms. Data presented here is the change from Day 1 to Day 7.

  Day 7

• Mean Change in Plasma Volume

  Volumex is albumin labeled with the iodine isotope I-131 and is an FDA-approved method used to determine plasma volume. A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Day 1 and day 7 measures of blood collection will be compared between intervention and placebo arms. Data presented here is the change from Day 1 to Day 7.

  Day 7

Secondary Outcomes (4)

• Mean Change in Serum Creatinine Concentration

  Daily for 7-days

• Mean Change in Cystatin C Concentration

  Daily for 7-days

• Mean Change in Chloride Concentration

  Daily for 7-days

• Mean Change in Bicarbonate Concentration

  Daily for 7-days

Study Arms (2)

Lysine Chloride

EXPERIMENTAL

Patients will be randomized to receive either lysine chloride or placebo. Patients will receive the study drug thrice daily for 5 days of randomized therapy, starting after the completion of a blood volume assessment.

Drug: Lysine Chloride

Placebo

PLACEBO COMPARATOR

Patients will be randomized to receive either lysine chloride or placebo. Patients will receive the study drug thrice daily for 5 days of randomized therapy, starting after the completion of a blood volume assessment.

Other: Placebo

Interventions

Lysine Chloride DRUG

Patients will receive the study drug thrice daily for 5 days.

Lysine Chloride

Placebo OTHER

Patients will receive the placebo thrice daily for 5 days.

Placebo

Eligibility Criteria

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

You may qualify if:

• 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
• Chronic loop diuretic therapy with ≥ 40 mg of furosemide equivalents
• Serum chloride \<102 mmol/L

You may not qualify if:

• Inability to commit to or comply with the rigorous 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 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
• Serum pH \<7.3
• 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 \>300 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

Sponsors & Collaborators

• Yale University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

Location

Results Point of Contact

• Title: Jeffrey Testani, MD, MTR
• Organization: Yale School of Medicine

jeffrey.testani@yale.edu

(203) 785-7191

Study Officials

• Jeffrey M Testani, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: February 22, 2018
• Study Start: January 15, 2019
• Primary Completion: August 30, 2025
• Study Completion: August 30, 2025
• Last Updated: September 23, 2026
• Results First Posted: September 23, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)