An Early Phase 1 interventional study of Lysine Chloride and Placebo in Decompensated Heart Failure, sponsored by Yale University. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-23.
Sponsored by Yale University · Early Phase 1, Interventional, and Diagnostic
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.
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.
Stable heart failure as defined by:
Exclusion Criteria:
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
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
Patients will receive the study drug thrice daily for 5 days.
Patients will receive the placebo thrice daily for 5 days.
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.
Time frame: 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.
Time frame: Day 7
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Daily for 7-days
| Milestone | Lysine Chloride, Then Placebo | Placebo, Then Lysine Chloride |
|---|---|---|
| Started | 11 | 9 |
| Completed | 11 | 9 |
| Not completed | 0 | 0 |
| Milestone | Lysine Chloride, Then Placebo | Placebo, Then Lysine Chloride |
|---|---|---|
| Started | 11 | 9 |
| Completed | 11 | 9 |
| Not completed | 0 | 0 |
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.
| milliliters | Lysine Chloride | Placebo |
|---|---|---|
| Mean Change in Blood Volume | -275 (-453 to -97) | 73 (-161 to 308) |
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.
| milliliters | Lysine Chloride | Placebo |
|---|---|---|
| Mean Change in Plasma Volume | -152 (-277 to -26) | 91 (-77 to 259) |
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.
| mg/dL per day | Lysine Chloride | Placebo |
|---|---|---|
| Mean Change in Serum Creatinine Concentration | -0.001 (-0.013 to 0.011) | 0.003 (-0.009 to 0.014) |
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.
| mg/L per day | Lysine Chloride | Placebo |
|---|---|---|
| Mean Change in Cystatin C Concentration | -0.023 (-0.036 to -0.009) | -0.009 (-0.023 to 0.004) |
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.
| mmol/L per day | Lysine Chloride | Placebo |
|---|---|---|
| Mean Change in Chloride Concentration | 1.2 (0.9 to 1.6) | 0.0 (-0.4 to 0.4) |
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.
| mmol/L per day | Lysine Chloride | Placebo |
|---|---|---|
| Mean Change in Bicarbonate Concentration | -1.4 (-1.7 to -1.0) | -0.4 (-0.7 to -0.01) |
Collected over approximately 20 days. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Lysine Chloride | 0/20 (0%) | 0/20 (0%) | 13/20 (65%) |
| Placebo | 0/20 (0%) | 0/20 (0%) | 7/20 (35%) |
| Event | Lysine Chloride | Placebo |
|---|---|---|
| DiarrheaGastrointestinal disorders | 7/20 | 2/20 |
| ConstipationGastrointestinal disorders | 0/20 | 1/20 |
| TremorsNervous system disorders | 0/20 | 1/20 |
| DizzinessNervous system disorders | 1/20 | 1/20 |
| HypertensionVascular disorders | 0/20 | 1/20 |
| HypotensionVascular disorders | 0/20 | 1/20 |
| Sore throatRespiratory, thoracic and mediastinal disorders | 1/20 | 0/20 |
| MalaiseGeneral disorders | 1/20 | 0/20 |
| NauseaGastrointestinal disorders | 1/20 | 0/20 |
| CrampingMusculoskeletal and connective tissue disorders | 1/20 | 0/20 |
| Age, Continuous(years) | Lysine Chloride, Then Placebo | Placebo, Then Lysine Chloride | Total |
|---|---|---|---|
| Mean | 57.1 ± 8.5 | 51.4 ± 15.3 | 54.5 ± 12 |
| Sex: Female, Male(Participants) | Lysine Chloride, Then Placebo | Placebo, Then Lysine Chloride | Total |
|---|---|---|---|
| Female | 4 | 2 | 6 |
| Male | 7 | 7 | 14 |
| Race (NIH/OMB)(Participants) | Lysine Chloride, Then Placebo | Placebo, Then Lysine Chloride | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 5 | 2 | 7 |
| White | 5 | 7 | 12 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Region of Enrollment(participants) | Lysine Chloride, Then Placebo | Placebo, Then Lysine Chloride | Total |
|---|---|---|---|
| United States | 11 | 9 | 20 |
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Yale University