Decompensated Heart FailureEarly Phase 1NCT03440970
Mechanism and Effects of Manipulating Chloride Homeostasis in Stable Heart Failure
A Early Phase 1 study testing Lysine Chloride in people with Decompensated Heart Failure, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Decompensated Heart Failure
- What is being tested?
- Lysine Chloride
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jan 2019to 30 Aug 2025
- 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
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Decompensated Heart Failure
- Being tested
- Lysine Chloride, Placebo
- Keywords
- Chloride homeostasisH
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lysine ChlorideDrug
Patients will receive the study drug thrice daily for 5 days.
PlaceboOther
Patients will receive the placebo thrice daily for 5 days.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Day 7
Secondary outcomes (4)
Mean Change in Serum Creatinine Concentration
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
Mean Change in Cystatin C Concentration
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
Mean Change in Chloride Concentration
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
Mean Change in Bicarbonate Concentration
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 posted22 Feb 2018
- Study start15 Jan 2019
- Primary completion30 Aug 2025
- Study completion30 Aug 2025
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 Decompensated 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
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 20 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
- Investigators
- Jeffrey M Testani, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03440970
- Sponsor's protocol ID
- 2000022016
- Other IDs
- 1R01HL139629-01
- Status last verified
- Aug 2026
- First submitted
- 14 Feb 2018
- Last updated
- 23 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Popham J, Yasmin F, Ramani N, Okifo K, Rao V, Testani J, Wilson FP, Koutroulis I, Pierce RW. Mechanistic Specificity of Capillary Leak Indices: Validation in Heart Failure as a Negative Control. Crit Care Med. 2026 Nov 1;54(11):2969-2976. doi: 10.1097/CCM.0000000000007313. Epub 2026 Aug 12.
PubMed 42584202
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanism and Effects of Manipulating Chloride Homeostasis in Stable Heart Failure
- ClinicalTrials.gov ID
- NCT03440970
- Acronym / sponsor ID
- 2000022016
- Conditions
- Decompensated Heart Failure
- Keywords
- Chloride homeostasisH
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 15 Jan 2019 (actual)
- Primary completion
- 30 Aug 2025 (actual)
- Study completion
- 30 Aug 2025 (actual)
- First posted
- 22 Feb 2018 (actual)
- Results
- Posted 23 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lysine Chloride | Experimental | Drug: Lysine ChloridePatients 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. |
| Placebo | Placebo comparator | Other: PlaceboPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Meticulous history of medical compliance and attendance of appointments
- Stable heart failure as defined by:
- 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
Key exclusion criteria (12 listed)
- 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
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 the study drug thrice daily for 5 days. | Drug | Lysine Chloride |
| PlaceboPatients will receive the placebo thrice daily for 5 days. | Other | Placebo |
Primary outcome
Mean Change in Blood Volume
Time frame: Day 7
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.
Mean Change in Plasma Volume
Time frame: Day 7
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.
4 secondary outcomes
Mean Change in Serum Creatinine Concentration
Time frame: Daily for 7-days
Mean Change in Cystatin C Concentration
Time frame: Daily for 7-days
Mean Change in Chloride Concentration
Time frame: Daily for 7-days
Mean Change in Bicarbonate Concentration
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 23 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42584202Popham J, Yasmin F, Ramani N, Okifo K, Rao V, Testani J, Wilson FP, Koutroulis I, Pierce RW. Mechanistic Specificity of Capillary Leak Indices: Validation in Heart Failure as a Negative Control. Crit Care Med. 2026 Nov 1;54(11):2969-2976. doi: 10.1097/CCM.0000000000007313. Epub 2026 Aug 12.
- Individual participant dataSharing planned: No
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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.
Jeffrey M Testani, MD principal investigator
Yale University
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 Decompensated 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 8 inclusion and 12 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 23 Sep 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 23 Sep 2026). 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?
Mean Change in Blood Volume (time frame: Day 7). The study lists 2 primary outcomes in all. 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 NCT03440970, 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 23 Sep 2026.