Investigating the effects of chloride supplementation in heart failure patients

Mechanism and Effects of Manipulating Chloride Homeostasis in Stable Heart Failure

Early Phase 1 Interventional Yale University · NCT03440970

This study is testing if adding chloride to the diet can help people with heart failure manage their electrolyte balance and overall health better.

Quick facts

PhaseEarly Phase 1
Study typeInterventional
Enrollment20 (estimated)
Ages18 Years and up
SexAll
SponsorYale University Academic / other
Locations1 site (New Haven, Connecticut)
Trial IDNCT03440970 on ClinicalTrials.gov

What this trial studies

This study aims to explore the effects of sodium-free chloride supplementation on electrolyte balance, volume status, and sodium avidity in patients with stable heart failure. It focuses on understanding chloride homeostasis, an area that has received limited attention compared to sodium. The study will be conducted in a controlled inpatient setting, allowing for extensive biobanking and analysis of biological samples. The findings could provide insights into the therapeutic potential of manipulating chloride levels in heart failure management.

Who should consider this trial

Good fit: Ideal candidates are patients with stable heart failure, an ejection fraction of less than 40%, and specific electrolyte levels.

Not a fit: Patients with recent hospitalizations, those on certain diuretics, or with metabolic acidosis may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved management strategies for patients with heart failure by optimizing chloride homeostasis.

How similar studies have performed: While chloride homeostasis has been less studied, this approach is novel and could provide new insights into heart failure treatment.

Eligibility criteria

Show full inclusion / exclusion 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

Where this trial is running

New Haven, Connecticut

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Decompensated Heart FailureChloride homeostasisH
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.