Lysine Chloride for Heart Failure
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Yale University
Approved in 4 jurisdictions
Trial Summary
What is the purpose of this trial?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.
Is the drug Lysine Chloride a promising treatment for heart failure?Lysine Chloride, also known as L-Lysine, is a promising treatment because it is an essential amino acid that plays a role in various bodily functions. It is widely used as a supplement and has potential therapeutic uses in cardiovascular diseases, which includes heart failure. Its safety and efficacy have been evaluated in various contexts, suggesting it could be beneficial.510111213
What safety data is available for Lysine Chloride in heart failure treatment?The provided research does not contain specific safety data for Lysine Chloride or its variants in the treatment of heart failure. The studies focus on other treatments and conditions related to heart failure, such as lisinopril, sodium chloride intake, and electrolyte imbalances like hypochloremia and hyponatremia. Therefore, no direct safety data for Lysine Chloride in heart failure is available from these sources.1791415
What data supports the idea that Lysine Chloride for Heart Failure is an effective treatment?The available research does not provide any data supporting the effectiveness of Lysine Chloride for Heart Failure. Instead, the studies focus on enalapril, an ACE inhibitor, which has been shown to improve heart function and reduce mortality in patients with heart failure. Enalapril is highlighted as a significant treatment option, offering benefits such as improved exercise capacity and reduced heart failure symptoms. There is no mention of Lysine Chloride in the context of heart failure treatment in the provided research.23468
Do I have to stop taking my current medications for this trial?The trial requires stopping metformin during the inpatient periods if it can be done safely. You cannot use thiazide diuretics or chloride-containing medications providing more than 5 mmol/day if they can't be discontinued or substituted. Other medications are not specifically mentioned, so consult with the trial team.
Eligibility Criteria
This trial is for stable heart failure patients with an ejection fraction below 40%, on chronic loop diuretic therapy, and a serum chloride level under 102 mmol/L. They must have no hospitalizations in the past 90 days, be on evidence-based treatments, and have a history of following medical advice. Exclusions include those unable to follow the study protocol, using certain medications like metformin or thiazide diuretics recently, with severe kidney issues or significant blood sugar problems.Exclusion Criteria
My hemoglobin level is below 8.0 g/dL.
I have issues controlling my bladder or emptying it completely.
I am taking a medication with more than 5 mmol/day of chloride that cannot be stopped.
My kidney function is very low or I am on dialysis.
I have had metabolic or respiratory acidosis in the past.
Treatment Details
The trial is testing how sodium-free chloride supplementation (Lysine Chloride) affects electrolyte balance and fluid status compared to a placebo in heart failure patients. The goal is to understand if manipulating chloride levels can improve heart function by studying changes in volume status and sodium retention.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Lysine ChlorideExperimental Treatment1 Intervention
Patients will be randomized to receive either lysine chloride or placebo. Patients will receive the study drug twice a day for 5 days of randomized therapy, starting after the completion of a blood volume assessment.
Group II: PlaceboPlacebo Group1 Intervention
Patients will be randomized to receive either lysine chloride or placebo. Patients will receive the study drug twice a day for 5 days of randomized therapy, starting after the completion of a blood volume assessment.
Lysine Chloride is already approved in United States, European Union, Japan, India for the following indications:
🇺🇸 Approved in United States as Lysine Hydrochloride for:
- Herpes simplex prophylaxis and treatment
- Lysinuric protein intolerance
- Nephroprotection
🇪🇺 Approved in European Union as Lysine Hydrochloride for:
- Herpes simplex prophylaxis and treatment
- Lysinuric protein intolerance
- Nephroprotection
- Schizophrenia
🇯🇵 Approved in Japan as Lysine Hydrochloride for:
- Herpes simplex prophylaxis and treatment
- Anxiety
🇮🇳 Approved in India as Lysine Hydrochloride for:
- Herpes simplex prophylaxis and treatment
- Lysinuric protein intolerance
- Nephroprotection
- Schizophrenia
- Muscle recovery
Find a clinic near you
Research locations nearbySelect from list below to view details:
Yale UniversityNew Haven, CT
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Who is running the clinical trial?
Yale UniversityLead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
References
Safety of long-term use of lisinopril for congestive heart failure. [2019]Early clinical experience with lisinopril suggested that it was well tolerated in congestive heart failure (CHF). An analysis of data from greater than 1,000 patients treated with lisinopril has been performed to examine the long-term safety of lisinopril in CHF. Of these, 620 have been studied for up to nearly 4 years, and a further 440 have been studied in comparative trials for 3 months. When patients who received lisinopril or placebo for the same period were compared, the proportion of lisinopril patients reporting an adverse event was 44.1% compared with 39.4% on placebo. Over a 4-year period, 205 patients (33.1%) discontinued treatment. About 33% of these died, 33% withdrew due to clinical adverse events, 21 (3.4%) were withdrawn because of adverse laboratory findings, and 56 (9.0%) withdrew for reasons unrelated to treatment. Sixteen patients (2.6%) withdrew because lisinopril was deemed ineffective. The most frequently reported drug-related adverse laboratory findings were increases in blood urea nitrogen, blood urea, serum creatinine, and plasma potassium. There appeared to be no differences in the pattern of adverse events with respect to the race of the patient. Elderly patients and those with the most severe forms of heart failure appeared to be at greater risk for an adverse event. Evaluation of the safety of lisinopril compared with enalapril, captopril, and digoxin in controlled clinical trials shows all the angiotensin-converting enzyme inhibitors to be equally well tolerated with a closely similar range of adverse events, suggesting that the satisfactory safety profile of lisinopril is shared by other drugs of this class.(ABSTRACT TRUNCATED AT 250 WORDS)
[Efficacy of long-term treatment with enalapril in patients with congestive heart failure]. [2013]Effects of enalapril on congestive heart failure and survival until 12 months have been evaluated in 60 patients with congestive heart failure (II, III, IV NYHA class) versus 60 control patients. Enalapril has been administered with digitalis and diuretic for 12 months 5 mg twice a day; in 60 control patients only digitalis and diuretic have been administered. Patients have been controlled every month during 12 months evaluating: NYHA class, time of exercise at treadmill, ejection time of left ventricle, speed index of ejection, cardiac output, systolic output, ECG, blood pressure, creatinine, BUN and electrolytes. After 12 months a significant increase (p less than 0.001) of systolic and cardiac output in patients with enalapril has been recorded. Also the increase of exercise time was more evident in patients with enalapril (p less than 0.01). The results show that long term treatment with enalapril in patients with congestive heart failure, improving cardiac performance, gives an hemodynamic and symptomatic benefit.
Enalapril. An update of its pharmacological properties and therapeutic use in congestive heart failure. [2018]Enalapril provides significant haemodynamic, symptomatic and clinical improvement when added to maintenance therapy with digitalis and diuretics in patients with congestive heart failure [NYHA (New York Heart Association) classes II to IV]. These effects are not attenuated during long term therapy. More significantly, a clinical study demonstrated that enalapril reduces mortality when added to established therapy in patients with severe congestive heart failure (NYHA class IV) refractory to digitalis, diuretics and other vasodilators. Thus, ACE inhibitors such as enalapril offer a significant advance in the treatment of congestive heart failure. Because these drugs improve symptoms in patients with classes II to IV failure, and reduce mortality in patients with severe heart failure, they should be considered as first choice adjuvant therapy when a vasodilator is needed in addition to conventional treatment with digitalis and diuretics.
When and how to use angiotensin-converting enzyme inhibition in congestive heart failure. [2019]Angiotensin-converting enzyme (ACE) inhibitors have been found effective in the treatment of congestive heart failure (CHF) and have been recommended as the first choice of vasodilator therapy by some observers. Favorable hemodynamic responses, apparent both at rest and during exercise, result from a considerable reduction in both systemic and pulmonary vascular resistance, apparently due to both the arterial and venodilating effects of these agents. In addition, the recently reported results of the Cooperative North Scandinavian Enalapril Survival Study demonstrate that ACE inhibitors reduce mortality rates in patients with CHF. The etiology of heart failure does not seem to predict clinical response to ACE inhibitors, nor do acute resting and exercise hemodynamic responses. A weak relation has been found between plasma renin activity and short-term hemodynamic and clinical responses, but this association is not evident over the long term. Therefore, a trial of therapy with ACE inhibitors is necessary to judge efficacy in an individual patient with advanced CHF symptoms. Two such agents--captopril and enalapril--are available. The former has a more rapid onset and shorter duration of action, whereas the latter may be given on a twice-daily basis, simplifying chronic therapy.
The metabolic roles, pharmacology, and toxicology of lysine. [2019]L-lysine monohydrochloride (LMH) is widely available to the public as a nonprescription oral supplement. Most of the pharmaceutical-grade product is used as a suppressant of recurrent herpes simplex infections. Recent publications indicate the possibility of other therapeutic uses, e.g., in cardiovascular disease and osteoporosis. These and other potential applications are surveyed and evaluated in this review with suggestions for further study. Data on toxicity are reviewed and recommendations made regarding safety of chronic dosage levels.
Long-term survival in severe heart failure in patients treated with enalapril. Ten year follow-up of CONSENSUS I. [2019]The CONSENSUS trial was the first study to show prognostic improvement by an ACE inhibitor. Patients in NYHA class IV heart failure were treated with enalapril or placebo. After study completion (average 183 days) all patients were offered open-label enalapril therapy. This paper reports on the survival at the 10-year follow up of the patients randomized in the CONSENSUS trial.
Treatment options for hyponatremia in heart failure. [2021]Hyponatremia is independently associated with adverse outcomes in patients with congestive heart failure (CHF). The primary cause of hyponatremia in CHF is the inappropriate secretion of the antidiuretic hormone, arginine vasopressin (AVP). The binding of AVP to V(2) receptors in the renal collecting duct promotes water retention, a process that can lead to dilutional hyponatremia as well as increased ventricular preload. AVP could also exacerbate the course of CHF by interacting with V(1A) receptors on vascular smooth muscle cells and myocytes. Conventional treatment of hyponatremia in CHF is based largely on water restriction, which is neither effective nor well tolerated. Current research is exploring V(2)- and dual V(1A)/V(2)-receptor antagonism for the treatment of hyponatremia, as well as for the congestion and edema associated with CHF, since AVP-receptor antagonists may offer benefits in comparison to conventional loop diuretics. Clinical trials in patients with hyponatremia and CHF using both selective and nonselective vasopressin antagonists have demonstrated the effectiveness of these agents in correcting this common electrolyte abnormality.
Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) study. [2013]The renin-angiotensin-aldosterone system (RAAS) represents a key therapeutic target in heart failure (HF) management. However, conventional agents that block this system induce a reflex increase in plasma renin activity (PRA), which may lead to RAAS 'escape'. Direct renin inhibitors (DRIs) have been developed that decrease PRA and thus may provide a greater RAAS blockade. Aliskiren is the first orally active DRI. Plasma levels of B-type natriuretic peptide (BNP) have been observed to be reduced with aliskiren compared with placebo. The aim of the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failuRE (ATMOSPHERE) study is to evaluate the effect of both aliskiren and enalapril monotherapy and aliskiren/enalapril combination therapy on cardiovascular death and HF hospitalization in patients with chronic systolic HF, NYHA functional class II-IV symptoms, and elevated plasma levels of BNP. Methods Patients tolerant to at least 10 mg or equivalent of enalapril will undergo an open-label run-in period where they receive enalapril then aliskiren. Approximately 7000 patients tolerating this run-in period will then be randomized 1:1:1 to aliskiren monotherapy, enalapril monotherapy, or the combination. The primary endpoints of ATMOSPHERE are (i) whether the aliskiren/enalapril combination is superior to enalapril monotherapy in delaying time to first occurrence of cardiovascular death or HF hospitalization and (ii) whether aliskiren monotherapy is superior or at least non-inferior to enalapril monotherapy on this endpoint. Perspective The ATMOSPHERE study will definitively determine the role of a DRI strategy additional to or as an alternative to conventional RAAS blockade in patients with chronic systolic HF.
Low serum chloride in patients with chronic heart failure: clinical associations and prognostic significance. [2019]Low serum chloride is common in patients with chronic heart failure (CHF) and is associated with worse outcomes. We investigated the clinical and prognostic associations, including cause of death associations, of low serum chloride in patients referred to a secondary care clinic with suspected heart failure.
Safety and efficacy of l-lysine monohydrochloride and l-lysine sulfate produced using Corynebacterium glutamicum CGMCC 7.266 for all animal species. [2020]Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on l-lysine monohydrochloride and l-lysine sulfate produced using Corynebacterium glutamicum CGMCC 7.266 when used as a nutritional additive in feed and water for drinking for all animal species. The active substance is l-lysine and it is produced in two different forms (monohydrochloride or sulfate salts). None of those forms pose any safety concern associated with the genetic modification of the production strain. l-Lysine HCl and l-lysine sulfate produced by C. glutamicum CGMCC 7.266 are considered safe for the target species, for the consumer and for the environment. For both products, the FEEDAP Panel has concerns regarding the safety for the target species when the additives are administered via feed and water for drinking, simultaneously. In the absence of data, the FEEDAP Panel cannot conclude on the safety of both forms of the additive for the user. The products under assessment are considered efficacious sources of the amino acid l-lysine for all animal species. For these products to be as efficacious in ruminants as in non-ruminant species, they require protection against degradation in the rumen.
Safety and efficacy of concentrated liquid l-lysine (base) and l-lysine monohydrochloride produced by fermentation with Corynebacterium casei KCCM 80190 as feed additives for all animal species. [2023]Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on concentrated liquid l-lysine (base) and l-lysine monohydrochloride (HCl) produced using Corynebacterium casei KCCM 80190 when used as nutritional additives in feed and water for drinking for all animal species. The active substance is l-lysine. The production strain is genetically modified. It does not carry acquired antimicrobial resistance genes and no viable cells of the production strain nor its DNA were detected in the final products. Therefore, the additives do not pose any safety concern regarding the genetic modifications. Concentrated liquid l-lysine (base) and l-lysine HCl produced by C. casei KCCM 80190 do not represent a risk for the target species, the consumer and the environment. From the results of studies on the safety for the user of concentrated liquid l-lysine (base) and l-lysine HCl produced by a different production strain, it was possible to conclude on the safety for the user of the products under assessment. Concentrated liquid l-lysine (base) produced by C. casei KCCM 80190 is considered hazardous by inhalation, not irritant to skin and eyes and it is not a skin sensitiser. l-Lysine HCl produced by C. casei KCCM 80190 is considered hazardous by inhalation, it is not irritant to skin but mildly irritant to eyes and it is not a skin sensitiser. Concentrated liquid l-lysine (base) and l-lysine HCl are considered efficacious sources of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as in non-ruminant species, it would require protection against degradation in the rumen.
Safety and efficacy of a feed additive consisting of l-lysine monohydrochloride and l-lysine sulfate produced by Corynebacterium glutamicum CGMCC 14498 for all animal species (Kempex Holland BV). [2022]Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of l-lysine monohydrochloride (l-lysine HCl) and l-lysine sulfate produced by Corynebacterium glutamicum (C. glutamicum) CGMCC 14498 as a nutritional feed additive for all animal species. The active substance is l-lysine and it is produced in two different forms (monohydrochloride or sulfate). The production strain C. glutamicum CGMCC 14498 and its recombinant DNA were not detected in the final products. The products l-lysine HCl and l-lysine sulfate do not pose any safety concern associated with the production strain. l-Lysine HCl and l-lysine sulfate produced by C. glutamicum CGMCC 14498 are considered safe for the target species. When using l-lysine sulfate, the background sulfur/sulfate content in the compound feed should be taken into account. l-Lysine HCl and l-lysine sulfate produced by C. glutamicum CGMCC 14498 are safe for the consumer and the environment. In the absence of data, the FEEDAP Panel cannot conclude on the potential of l-lysine HCl produced by the strain C. glutamicum CGMCC 14498 to be toxic by inhalation, and on the potential of l-lysine HCl and l-lysine sulfate produced by the above-mentioned strain to be irritant to skin or eyes, or on their potential to be dermal sensitisers. l-Lysine HCl and l-lysine sulfate produced by C. glutamicum CGMCC 14498 are considered efficacious sources of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as in non-ruminant species, this would require protection against degradation in the rumen.
Safety and efficacy of a feed additive consisting of l-lysine monohydrochloride and l-lysine sulfate produced by fermentation with Corynebacterium glutamicumCGMCC 17927 for all animal species (Barentz Animal Nutrition B.V.). [2022]Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on l-lysine monohydrochloride and l-lysine sulfate produced by Corynebacterium glutamicum CGMCC 17927, when used as a nutritional additive in feed and water for drinking for all animal species. The active substance is l-lysine, and it was produced in two different forms: monohydrochloride (HCl) or sulfate salts. The production strain was genetically modified. Neither viable cells nor recombinant DNA of the production strain were detected in the final products. Therefore, the Panel concluded that the additives did not pose any safety concern regarding the production strain. The use of l-lysine HCl and l-lysine sulfate produced by the strain C. glutamicum CGMCC 17927 in supplementing feed to compensate for l-lysine deficiency in feedingstuffs was safe for the target species. The FEEDAP Panel identified risks of nutritional imbalances and hygienic concerns for amino acids when administered simultaneously in feed and in water for drinking. The use of both forms of l-lysine produced by fermentation using C. glutamicum CGMCC 17927 in animal nutrition was considered safe for the consumers and for the environment. Exposure of users through inhalation to l-lysine HCl and l-lysine sulfate produced with C. glutamicum CGMCC 17927 was considered very likely. In absence of data, the FEEDAP Panel could not conclude on the potential of both forms of the additive to be irritant for skin and eyes or to be dermal sensitisers. l-Lysine HCl and l-lysine sulfate were considered as efficacious sources of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as in non-ruminant species, it would require protection against degradation in the rumen.
Effect of renal function on the prognostic importance of chloride in patients with heart failure. [2023]Hypochloremia has recently gained interest as a potential marker of outcomes in patients with heart failure (HF). The exact pathophysiologic mechanism linking hypochloremia to HF is unclear but is thought to be mediated by chloride-sensitive proteins and channels located in kidneys. This analysis aimed to understand whether renal dysfunction (RD) affects the association of hypochloremia with mortality in patients with HF. Using data from a nationwide registry, 438 cases with complete data on serum chloride concentration and 1-year survival were included in the analysis. Patients with an estimated glomerular filtration rate of <60 mL/min/m2 at baseline were accepted as having RD. Hypochloremia was defined as a chloride concentration <96 mEq/L at baseline. For HF patients without RD at baseline, patients with hypochloremia had a significantly higher 1-year all-cause mortality than those without hypochloremia (41.6% vs 13.0%, log-rank p < 0.001) and the association remained significant after multivariate adjustment (odds ratio (OR): 2.55, 95% confidence interval (CI): 1.25-5.21). The evidence supporting the association was very strong in this subgroup (Bayesian Factor (BF)10: 48.25, log OR: 1.56, 95% CI: 0.69-2.43). For patients with RD at baseline, there was no statistically significant difference for 1-year mortality for patients with or without hypochloremia (36.3% vs 29.7, log-rank p = 0.35) and there was no evidence to support an association between hypochloremia and mortality (BF10: 1.18, log OR :0.66, 95% CI: -0.02 to 1.35). In patients with HF, the association between low chloride concentration and mortality is limited to those without RD at baseline.
Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure: A Randomized, Placebo-Controlled, Double-Blind Study. [2023]Evidence for modulating the sodium chloride (NaCl) intake of patients hospitalized with acute heart failure (AHF) is inconclusive. Salt restriction may not benefit; hypertonic saline may aid diuresis.