Back to resultsEfficacy of Para-Tyrosine Supplementation on the Survival and Clinical Outcome in Patients With Sepsis
Primary Purpose
Sepsis
Status
Not yet recruiting
Phase
Phase 2
Locations
Hungary
Study Type
Interventional
Intervention
Para-Tyrosine supplementation
Placebo solution
Sponsored by
About this trial
This is an interventional prevention trial for Sepsis focused on measuring sepsis, para-Tyrosine, ortho-Tyrosine, meta-Tyrosine
Eligibility Criteria
Inclusion Criteria:
Subjects must meet the following inclusion criteria to be eligible for the study:
- Are able to provide written informed consent (either the patient or the person entitled by legislation to consent on behalf of the patient)
- Male and female patients ≥ 18 years
- Have a current primary diagnosis of sepsis based on the the third international consensus definitions for sepsis and septic shock (Sepsis-3)Willing and able to comply with all aspects of the protocol
- Females of childbearing potential must have negtive serum pregnancy test az screening. (All females will be considered to be of childbearing potential unless they are postmenopausal i.e. amenorrheic for at least 12 consecutive months, in the appropriate age group and without other known or suspected cause or have been sterilized surgically i.e. bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)
Exclusion Criteria:
Subjects must not have any of the following criteria to be eligible for the study:
- Females who are pregnant (positive β-hCG test at screening) or breastfeeding
- chronic use of steroids or immunosuppressive drugs within the past 3 months
- other therapy influencing the immune system within the past 3 months (radiotherapy, chemotherapy etc.)
- malignant hematologic disease
- jejunal tube feeding
- any other significant illness in the medical history ongoing in the preceeding 1 month, which may have an influence on the survival and clinical outcome of the patients (e.g severe chronic heart failure NYHA III-IV., AMI, stroke, major surgery, COPD, renal failure, hepatic failure, hepatic cirrhosis etc.)
- Life expectancy less, than 1 months according to the judgement of the Investigator (even without significant illness, due to age or general status of the patient)
- Hypersensitivity to any of the excipients of the study product
- Known to be human immunodeficiency virus (HIV) positive
- Active viral hepatitis (B or C) as demonstrated by positive serology
- History of drug or alcohol dependency or abuse within approximately the last 2 years
Sites / Locations
- 2nd Department of Medicine and Nephrological Center
- Department of Anaesthesiology and Intensive Care
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Para-Tyrosine intervention
Placebo
Arm Description
The patients will receive the study drug during their stay at the ICU but for a maximum of 7 days. Study drug will be dispensed by a nominated member of the study team and administered to the patients by the ICU staff via nasogastric tube in form of oral suspension. The content of the hard capsules will be dissolved in 20 ml of tap water before the dosing. Drug name: Tyrosine. Strength 500 mg. Oral dose form: hard capsule. Number of Dispensed at frequency of 3x2 g daily. Duration of administration: 4 to 7 days.
The patients will receive the study drug during their stay at the ICU but for a maximum of 7 days. Study drug will be dispensed by a nominated member of the study team and administered to the patients by the ICU staff via nasogastric tube in form of oral suspension. The content of the hard capsules will be dissolved in 20 ml of tap water before the dosing. Drug name: Placebo.. Strength N/A. Oral dose form: capsule matching to Tyrosine capsule. Number of Dispnsed an frequency 3x2 g daily. Duration of administration: 4 to 7 days.
Outcomes
Primary Outcome Measures
Mortality
Comparison of mortality starting from randomization and start of treatment (which should be on the same day) during the period of ICU stay between the active treatment group and placebo group.
Secondary Outcome Measures
Effect of para-Tyrosine supplementation on the clinical outcome of sepsis
The investigators wish to evaluate whether supplementation of p-Tyr has effect on clinical outcome (appearance of organ failures due to sepsis: renal failure, respiratory failure, coagulation disorders, hepatic failure, cardiac failure, need for vasopressors, CH balance, nitrogen-balance) of sepsis compared to placebo in patients receiving appropriate standard care. The investigators wish to assess wether para-Tyrosine supplementation can ameliroate the time course and severity of sepsis
Long term effects of para-Tyrosine supplementation on survival
The investigators would like to evaluate the effect of p-Tyr supplementation on 28-day survival of patients with sepsis based on the patients' electronic documentation
Reduction in the time of ICU stay
The investigators shall evaluate, whether the treatment can reduce the time of the ICU stay
Overall mortality
The investigators will evaluate the effect on overall mortality of patients with sepsis during their hospitalization
Hospitalization time
The investigators will evaluate the effect of p-Tyr supplemetation on the overall hospitalization time
Safety and tolerability of para-Tyrosine supplementation (Incidence of Treatment-Emergent Adverse Events)
The investigators wish to evaluate the safety of the investigational product: Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events shall be recorded, using physiological parameters such as impairment in renal and hepatic function, bone marrow toxicity, severe blood pressure changes, tachycardia etc.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03278730
Brief Title
Efficacy of Para-Tyrosine Supplementation on the Survival and Clinical Outcome in Patients With Sepsis
Official Title
Phase 2 Single Center, Randomized, Placebo-controlled, Double-blind, Parallel Group Study to Evaluate Efficacy of Para-Tyrosine Supplementation on the Survival and Clinical Outcome in Patients With Sepsis
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
February 1, 2024 (Anticipated)
Primary Completion Date
February 1, 2025 (Anticipated)
Study Completion Date
February 28, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pecs
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Meta-and ortho-Tyrosine are known markers of oxidative stress, while the physiological isomer, para-Tyrosine is suggested the antagonize the effects of meta- and ortho-Tyrosine. The changes in the serum levels of meta- and ortho-Tyrosine have been found to be paralel to that of the common sepsis markers. The hypothesis of the study is, that supplementation of para-Tyrosine (p-Tyr) in the early phase of sepsis may diminish some specific inflammatory procedures and thus may have a favourable impact on the disease progress, and consequently on the mortality.
Detailed Description
Data suggest, that among the amino acids, the meta- and ortho- isomers of tyrosine are potential markers of oxydative stress. The changes in their serum levels (and urinary excretion) in sepsis were found to be parallel to the changes of the common inflammatory markers, i.e. C-reactive protein (CRP) and pro-calcitonin (PCT). However, para-Tyrosine, which is the isomer physiologically present, seemed to have different kinetics. Furthermore, according to the observations, pathological processes linked to the inflammation could be attenuated or partially or completely reversed by para-tyrosine.
The hypothesis of the study is, that supplementation of para-Tyrosine (p-Tyr) in the early phase of sepsis may diminish some specific inflammatory procedures and thus may have a favourable impact on the disease progress, and consequently on the mortality.
The primary objective of the study is to evaluate, whether oral P-Tyr supplementation reduces mortality compared to placebo group during the ICU stay in patients with sepsis.
The primary endpoint is the comparison of mortality starting from randomization and start of treatment (which should be on the same day) during the period of ICU stay between the active treatment group and placebo group. The secondary objectives of the study are:
to evaluate whether supplementation of p-Tyr has effect on clinical outcome of sepsis compared to placebo in patients receiving appropriate standard care; to evaluate the effect of p-Tyr supplementation on 28-day survival of patients with sepsis; to evaluate, whether the treatment can reduce the time of the ICU stay, to evaluate the effect on overall mortality of patients with sepsis during their hospitalization, to evaluate the effect of p-Tyr supplemetation on the overall hospitalization time, to evaluate the safety of the investigational product. The investigators wish to explore To explore whether serum level of p-Tyr can be maintained with the oral supplementation; dynamics and interrelation of the levels of oxidative stress markers (o- and m-Tyr) and the physiologic isomer of Tyr (p-Tyr) and Phenylalanine (Phe) and the correlation of o-Tyr and m-Tyr serum levels and other parameters of inflammation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis
Keywords
sepsis, para-Tyrosine, ortho-Tyrosine, meta-Tyrosine
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
The objective is to evaluate, whether p-Tyr supplementation reduces the ICU mortality of the patients with sepsis comparing to placebo group
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
296 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Para-Tyrosine intervention
Arm Type
Active Comparator
Arm Description
The patients will receive the study drug during their stay at the ICU but for a maximum of 7 days.
Study drug will be dispensed by a nominated member of the study team and administered to the patients by the ICU staff via nasogastric tube in form of oral suspension. The content of the hard capsules will be dissolved in 20 ml of tap water before the dosing.
Drug name: Tyrosine. Strength 500 mg. Oral dose form: hard capsule. Number of Dispensed at frequency of 3x2 g daily. Duration of administration: 4 to 7 days.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
The patients will receive the study drug during their stay at the ICU but for a maximum of 7 days.
Study drug will be dispensed by a nominated member of the study team and administered to the patients by the ICU staff via nasogastric tube in form of oral suspension. The content of the hard capsules will be dissolved in 20 ml of tap water before the dosing.
Drug name: Placebo.. Strength N/A. Oral dose form: capsule matching to Tyrosine capsule. Number of Dispnsed an frequency 3x2 g daily. Duration of administration: 4 to 7 days.
Intervention Type
Drug
Intervention Name(s)
Para-Tyrosine supplementation
Intervention Description
Patients will recieve the study drug during their stay at the ICU, but for a maximum of 7 days. The study drug is 3x2 gramms of para-Tyrosine, which will be dispensed and administered in a form of oral suspension via a nasogastric tube.
Intervention Type
Drug
Intervention Name(s)
Placebo solution
Intervention Description
Patients will recieveplacebo during their stay at the ICU, but for a maximum of 7 days. The study drug is 3x2 gramms of placebo, which will be dispensed and administered in a form of oral suspension via a nasogastric tube.
Primary Outcome Measure Information:
Title
Mortality
Description
Comparison of mortality starting from randomization and start of treatment (which should be on the same day) during the period of ICU stay between the active treatment group and placebo group.
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Effect of para-Tyrosine supplementation on the clinical outcome of sepsis
Description
The investigators wish to evaluate whether supplementation of p-Tyr has effect on clinical outcome (appearance of organ failures due to sepsis: renal failure, respiratory failure, coagulation disorders, hepatic failure, cardiac failure, need for vasopressors, CH balance, nitrogen-balance) of sepsis compared to placebo in patients receiving appropriate standard care. The investigators wish to assess wether para-Tyrosine supplementation can ameliroate the time course and severity of sepsis
Time Frame
30 days
Title
Long term effects of para-Tyrosine supplementation on survival
Description
The investigators would like to evaluate the effect of p-Tyr supplementation on 28-day survival of patients with sepsis based on the patients' electronic documentation
Time Frame
28 days
Title
Reduction in the time of ICU stay
Description
The investigators shall evaluate, whether the treatment can reduce the time of the ICU stay
Time Frame
30 days
Title
Overall mortality
Description
The investigators will evaluate the effect on overall mortality of patients with sepsis during their hospitalization
Time Frame
60 days
Title
Hospitalization time
Description
The investigators will evaluate the effect of p-Tyr supplemetation on the overall hospitalization time
Time Frame
60 days
Title
Safety and tolerability of para-Tyrosine supplementation (Incidence of Treatment-Emergent Adverse Events)
Description
The investigators wish to evaluate the safety of the investigational product: Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events shall be recorded, using physiological parameters such as impairment in renal and hepatic function, bone marrow toxicity, severe blood pressure changes, tachycardia etc.
Time Frame
60 days
Other Pre-specified Outcome Measures:
Title
Effect of supplementation on the maintanance of the serum level of para-Tyrosine
Description
The investigators will explore using high performance liquid cromatography (HPLC) whether serum level of p-Tyr can be maintained with the oral supplementation
Time Frame
30 days
Title
Assessment of pharmacodynamics
Description
Exploration of the dynamics and interrelation of the levels of oxidative stress markers (o- and m-Tyr) and the physiologic isomer of Tyr (p-Tyr) and Phenylalanine (Phe)
Time Frame
10 days
Title
Correlation of o-Tyr and m-Tyr serum levels and other parameters of inflammation
Description
The investigators will assess the correlation of o-Tyr and m-Tyr serum levels and other parameters of inflammation
Time Frame
10 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must meet the following inclusion criteria to be eligible for the study:
Are able to provide written informed consent (either the patient or the person entitled by legislation to consent on behalf of the patient)
Male and female patients ≥ 18 years
Have a current primary diagnosis of sepsis based on the the third international consensus definitions for sepsis and septic shock (Sepsis-3)Willing and able to comply with all aspects of the protocol
Females of childbearing potential must have negtive serum pregnancy test az screening. (All females will be considered to be of childbearing potential unless they are postmenopausal i.e. amenorrheic for at least 12 consecutive months, in the appropriate age group and without other known or suspected cause or have been sterilized surgically i.e. bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)
Exclusion Criteria:
Subjects must not have any of the following criteria to be eligible for the study:
Females who are pregnant (positive β-hCG test at screening) or breastfeeding
chronic use of steroids or immunosuppressive drugs within the past 3 months
other therapy influencing the immune system within the past 3 months (radiotherapy, chemotherapy etc.)
malignant hematologic disease
jejunal tube feeding
any other significant illness in the medical history ongoing in the preceeding 1 month, which may have an influence on the survival and clinical outcome of the patients (e.g severe chronic heart failure NYHA III-IV., AMI, stroke, major surgery, COPD, renal failure, hepatic failure, hepatic cirrhosis etc.)
Life expectancy less, than 1 months according to the judgement of the Investigator (even without significant illness, due to age or general status of the patient)
Hypersensitivity to any of the excipients of the study product
Known to be human immunodeficiency virus (HIV) positive
Active viral hepatitis (B or C) as demonstrated by positive serology
History of drug or alcohol dependency or abuse within approximately the last 2 years
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
István Wittmann, MD,PhD,DSc
Phone
+3672536050
Email
istvan.wittmann@aok.pte.hu
First Name & Middle Initial & Last Name or Official Title & Degree
Gergő A Molnár, MD, PhD
Phone
+3672536050
Email
molnargergo1@yahoo.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
István Wittmann, MD,PhD,DSc
Organizational Affiliation
University of Pecs
Official's Role
Principal Investigator
Facility Information:
Facility Name
2nd Department of Medicine and Nephrological Center
City
Pécs
State/Province
Baranya
ZIP/Postal Code
7624
Country
Hungary
Facility Name
Department of Anaesthesiology and Intensive Care
City
Pécs
State/Province
Baranya
ZIP/Postal Code
7624
Country
Hungary
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lajos Bogar, MD, PhD, DSc
Phone
+3672536000
Email
bogar.lajos@pte.hu
First Name & Middle Initial & Last Name & Degree
Csaba Csontos, MD, PhD
Phone
+3672536000
Email
csaba.csontos@pte.hu
First Name & Middle Initial & Last Name & Degree
Diána Mühl, MD, PhD
First Name & Middle Initial & Last Name & Degree
Lívia Szélig, MD
12. IPD Sharing Statement
Plan to Share IPD
No
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Efficacy of Para-Tyrosine Supplementation on the Survival and Clinical Outcome in Patients With Sepsis
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