Efficacy of Para-Tyrosine Supplementation on the Survival and Clinical Outcome in Patients With Sepsis

November 30, 2023 updated by: István Wittmann, University of Pecs

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

296

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Hungary
    • Baranya
      • Pécs, Baranya, Hungary, 7624
        • 2nd Department of Medicine and Nephrological Center
      • Pécs, Baranya, Hungary, 7624
        • Department of Anaesthesiology and Intensive Care
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Diána Mühl, MD, PhD
        • Sub-Investigator:
          • Lívia Szélig, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Subjects must meet the following inclusion criteria to be eligible for the study:

  1. Are able to provide written informed consent (either the patient or the person entitled by legislation to consent on behalf of the patient)
  2. Male and female patients ≥ 18 years
  3. 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
  4. 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:

  1. Females who are pregnant (positive β-hCG test at screening) or breastfeeding
  2. chronic use of steroids or immunosuppressive drugs within the past 3 months
  3. other therapy influencing the immune system within the past 3 months (radiotherapy, chemotherapy etc.)
  4. malignant hematologic disease
  5. jejunal tube feeding
  6. 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.)
  7. 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)
  8. Hypersensitivity to any of the excipients of the study product
  9. Known to be human immunodeficiency virus (HIV) positive
  10. Active viral hepatitis (B or C) as demonstrated by positive serology
  11. History of drug or alcohol dependency or abuse within approximately the last 2 years

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Para-Tyrosine intervention

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.
Drug: Para-Tyrosine supplementation
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.
Placebo Comparator: Placebo

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.
Drug: Placebo solution
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: 30 days
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.
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of para-Tyrosine supplementation on the clinical outcome of sepsis
Time Frame: 30 days
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
30 days
Long term effects of para-Tyrosine supplementation on survival
Time Frame: 28 days
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
28 days
Reduction in the time of ICU stay
Time Frame: 30 days
The investigators shall evaluate, whether the treatment can reduce the time of the ICU stay
30 days
Overall mortality
Time Frame: 60 days
The investigators will evaluate the effect on overall mortality of patients with sepsis during their hospitalization
60 days
Hospitalization time
Time Frame: 60 days
The investigators will evaluate the effect of p-Tyr supplemetation on the overall hospitalization time
60 days
Safety and tolerability of para-Tyrosine supplementation (Incidence of Treatment-Emergent Adverse Events)
Time Frame: 60 days
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.
60 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of supplementation on the maintanance of the serum level of para-Tyrosine
Time Frame: 30 days
The investigators will explore using high performance liquid cromatography (HPLC) whether serum level of p-Tyr can be maintained with the oral supplementation
30 days
Assessment of pharmacodynamics
Time Frame: 10 days
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)
10 days
Correlation of o-Tyr and m-Tyr serum levels and other parameters of inflammation
Time Frame: 10 days
The investigators will assess the correlation of o-Tyr and m-Tyr serum levels and other parameters of inflammation
10 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pecs

Investigators

  • Principal Investigator: István Wittmann, MD,PhD,DSc, University of Pecs

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 1, 2025

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

February 28, 2027

Study Registration Dates

First Submitted

September 1, 2017

First Submitted That Met QC Criteria

September 7, 2017

First Posted (Actual)

September 12, 2017

Study Record Updates

Last Update Posted (Estimated)

December 1, 2023

Last Update Submitted That Met QC Criteria

November 30, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PTE-2015-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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