Heart FailureEarly Phase 1NCT03446651
Mechanism and Effects of Manipulating Chloride Homeostasis in Acute Heart Failure
A Early Phase 1 study testing Lysine Chloride in people with Heart Failure, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Lysine Chloride
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jul 2018to 7 Sep 2022
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Lysine Chloride, Placebo
- Keywords
- Sodium Homeostasis
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lysine ChlorideDrug
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.
PlaceboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Lysine Chloride | Experimental | 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. Receives: Drug: Lysine Chloride |
| Placebo | Placebo comparator | 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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. Daily measures of blood collection will be compared across the 7 day collection period between intervention and placebo arms.
Measured: Daily for 7 days
Secondary outcomes (5)
Change in Log NTpro-BNP
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.
Measured: Daily for 7-days
Change in Serum Creatinine
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.
Measured: Daily for 7-days
Change in Cystatin C
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.
Measured: Daily for 7-days
Change in Chloride
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.
Measured: Daily for 7-days
Change in Bicarbonate
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.
Measured: Daily for 7-days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2018
- Study start12 Jul 2018
- Primary completion7 Sep 2022
- Study completion7 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03446651
- Sponsor's protocol ID
- 2000022001
- Other IDs
- 1R01HL139629-01
- Status last verified
- Jul 2026
- First submitted
- 20 Feb 2018
- Last updated
- 31 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 37102974
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanism and Effects of Manipulating Chloride Homeostasis in Acute Heart Failure
- ClinicalTrials.gov ID
- NCT03446651
- Acronym / sponsor ID
- 2000022001
- Conditions
- Heart Failure
- Keywords
- Sodium Homeostasis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 12 Jul 2018 (actual)
- Primary completion
- 7 Sep 2022 (actual)
- Study completion
- 7 Sep 2022 (actual)
- First posted
- 27 Feb 2018 (actual)
- Results
- Posted 30 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lysine Chloride | Experimental | Drug: Lysine ChlorideParticipants 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. |
| Placebo | Placebo comparator | Other: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lysine ChloridePatients 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. | Drug | Lysine Chloride |
| PlaceboPatients 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. | Other | Placebo |
Primary outcome
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.
5 secondary outcomes
Change in Log NTpro-BNP
Time frame: Daily for 7-days
Change in Serum Creatinine
Time frame: Daily for 7-days
Change in Cystatin C
Time frame: Daily for 7-days
Change in Chloride
Time frame: Daily for 7-days
Change in Bicarbonate
Time frame: Daily for 7-days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37102974Kazory 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Lysine Chloride in people with Heart Failure, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Blood Volume (time frame: Daily for 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03446651, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.