Trial document




drksid header

  DRKS00016553

Trial Description

start of 1:1-Block title

Title

PPARgamma expression in T cells as a marker of orthopedic infectious disease progression

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

-

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

http://-

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

The aim of this study is to find a new diagnostic marker to detect joint / prosthesis infection or spinal infection at an early stage. An early diagnosis of these diseases is very important to initiate an efficient and targeted treatment of the infection. The expression of the transcription factor PPARgamma in T cells is considered as new diagnostic marker of infection. With this study, the authors aim to provide more accurate insights into this component of immune cells and to derive new diagnostic and therapeutic approaches to treat infectious diseases.
We will take a total of 8 blood samples within 14 days after the diagnosis of joint / prosthesis infection or spinal infection to determine the number of PPARgamma mRNA copies in T cells as well as the total count of T cell subsets.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

Previous clinical studies tried to influence the hyperinflammatory pathway using different approaches to decrease proinflammatory mediators. But the suppression of the hyperinflammatory response reduces the host’s ability to fight primary or secondary infections and therefore, this treatment regimen failed to significantly improve the outcome of infectious diseases.
However, the simultaneous release of anti-inflammatory mediators, as a component of the hypoinflammatory response, provokes T cell apoptosis. This T cell death produces immune paralysis, which is thought to be the main reason for the inability of the patient to fight infections. PPARgamma causes one of these anti-inflammatory responses and acts as a key regulator in apoptosis of activated T cells during sepsis.

Our research is based on the assumption that the mRNA expression of PPARgamma in T cells correlates with the severity of infectious orthopedic diseases like spondylodiscitis, joint or prosthesis infection and the appearance of inflammatory markers (C-reactive protein / Procalcitonin / erythrocyte sedimentation rate / number of leukocytes). In this study, we will isolate CD3+ T cells from the blood of infectious patients. After mRNA extraction, the measurement of PPARgamma mRNA expression will be taken by a reverse transcriptase quantitative real-time PCR. In order to determine the specific date of the T cell apoptosis, we will also perform a FACS analysis and measure the cell count of different T cell subpopulations in the blood of infectious patients. Targeted PPARgamma antagonization in T cells could be a novel therapeutic approach to prevent T cell depletion. It is essential to gain increasing knowledge about the exact expression profile of PPARgamma in T cells during infectious diseases.

end of 1:1-Block scientific synopsis
start of 1:1-Block forwarded Data

Do you plan to share individual participant data with other researchers?

No

end of 1:1-Block forwarded Data
start of 1:1-Block forwarded Data Content

Description IPD sharing plan:

Publication planned.
According to approval of the ethics comm. no transfer of the data is planned.

end of 1:1-Block forwarded Data Content
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00016553
  •   2019/02/27
  •   [---]*
  •   yes
  •   Approved
  •   212/18, Ethikkommission des Fachbereichs Humanmedizin der Johann-Wolfgang-Goethe-Universität Frankfurt am Main
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  • [---]*
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   M46.2 -  Osteomyelitis of vertebra
  •   M46.3 -  Infection of intervertebral disc (pyogenic)
  •   M46.4 -  Discitis, unspecified
  •   M46.1 -  Sacroiliitis, not elsewhere classified
  •   M46.5 -  Other infective spondylopathies
  •   M00 -  Pyogenic arthritis
  •   M01 -  Direct infections of joint in infectious and parasitic diseases classified elsewhere
  •   T84 -  Complications of internal orthopaedic prosthetic devices, implants and grafts
  •   M19 -  Other arthrosis
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Patients with diagnosed joint / prosthesis infection:
    In this study, we aim to investigate the T cell PPARgamma expression of orthopaedic infectious patients to test whether it is regulated during the infectious disease progression. This will provide further evidence on whether the T cell PPARgamma expression could potentially be used as a diagnostic marker for infection.
    In order to provide answers to these questions, we will determine the T cell count and T cell-specific mRNA PPARgamma expression derived from the blood of 100 patients with joint/protheses infection.
    The sampling starts on the day when the infection is diagnosed and continues, consecutively, for up to day 14.
    For each sample, 10 ml of EDTA blood will be taken with the routine blood withdrawal. The blood sample will be used for the analysis of the T cell count and T cell-specific mRNA PPARgamma expression. A total of 8 samples per patient will be examined (measurement time points: day 0, 1, 2, 4, 6, 8, 10 and 12 after diagnosis).
    The T-cell subpopulations will be enriched by magnetic separation. From these enriched cell populations, we will isolate RNA to determine the level of PPARgamma mRNA expression. The quantification (ng/cell) of PPARgamma mRNA (ng/cell) will be measured by quantitative PCR using an established PPARgamma plasmid standard.
    Finally medical patient data will be collected to define the Status of the infection and to assess potential comorbidities.
  •   Patients with diagnosed spondylodiscitis:
    In this study, we aim to investigate the T cell PPARgamma expression of orthopaedic infectious patients to test whether it is regulated during the infectious disease progression. This will provide further evidence on whether the T cell PPARgamma expression could potentially be used as a diagnostic marker for infection.
    In order to provide answers to these questions, we will determine the T cell count and T cell-specific mRNA PPARgamma expression derived from the blood of 50 patients with diagnosed spondylodscitis.
    The sampling starts on the day when the infection is diagnosed and continues, consecutively, for up to day 14.
    For each sample, 10 ml of EDTA blood will be taken with the routine blood withdrawal. The blood sample will be used for the analysis of the T cell count and T cell-specific mRNA PPARgamma expression. A total of 8 samples per patient will be examined (measurement time points: day 0, 1, 2, 4, 6, 8, 10 and 12 after diagnosis).
    The T-cell subpopulations will be enriched by magnetic separation. From these enriched cell populations, we will isolate RNA to determine the level of PPARgamma mRNA expression. The quantification (ng / cell) of PPARgamma mRNA (ng / cell) will be measured by quantitative PCR using an established PPARgamma plasmid standard.
    Finally medical patient data will be collected to define the Status of the infection and to assess potential comorbidities.
  •   Healthy donor:
    In this study, we aim to investigate the T cell PPARgamma expression of orthopaedic infectious patients to test whether it is regulated during the infectious disease progression. This will provide further evidence on whether the T cell PPARgamma expression could potentially be used as a diagnostic marker for infection.
    In order to provide answers to these questions, we will determine the T cell count and T cell-specific mRNA PPARgamma expression derived from the blood of infectious patients and compare it to healthy donors / operative patients without diagnosed infection.
    Due to the expected relative homogeneity of the healthy donors, the analysis of 20 donors should be sufficient. In order to ensure reproducibility, 2 samples of control donors are analyzed within 30 days.
    For each sample, 10 ml of EDTA blood will be taken. The blood sample will be used for the analysis of the T cell count and T cell-specific mRNA PPARgamma expression. A total of 2 samples per healthy donor will be examined (measurement time points: day 0 and 30).
    The T-cell subpopulations will be enriched by magnetic separation. From these enriched cell populations, we will isolate RNA to determine the level of PPARgamma mRNA expression. The quantification (ng / cell) of PPARgamma mRNA (ng / cell) will be measured by quantitative PCR using an established PPARgamma plasmid standard.
  •   Patients with elective surgery without evidence of infection:
    In this study, we aim to investigate the T cell PPARgamma expression of orthopaedic infectious patients to test whether it is regulated during the infectious disease progression. This will provide further evidence on whether the T cell PPARgamma expression could potentially be used as a diagnostic marker for infection.
    In order to provide answers to these questions, we will determine the T cell count and T cell-specific mRNA PPARgamma expression derived from the blood of infectious patients and compare it to healthy donors / operative patients without diagnosed infection.
    In order to provide answers to these questions, we will determine the T cell count and T cell-specific mRNA PPARgamma expression derived from the blood of 50 operative patients without evidence for infection.
    For each sample, 10 ml of EDTA blood will be taken with the routine blood withdrawal. The blood sample will be used for the analysis of the T cell count and T cell-specific mRNA PPARgamma expression. A total of 4 samples per patient will be examined (measurement time points: pre-OP, day 1, 2 and 7 after diagnosis).
    The T-cell subpopulations will be enriched by magnetic separation. From these enriched cell populations, we will isolate RNA to determine the level of PPARgamma mRNA expression. The quantification (ng / cell) of PPARgamma mRNA (ng / cell) will be measured by quantitative PCR using an established PPARgamma plasmid standard.
    Finally medical patient data will be collected to define the Status of the infection and to assess potential comorbidities.
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Non-randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Other
  •   Diagnostic
  •   Parallel
  •   N/A
  •   N/A
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

Primary outcome: PPARgamma mRNA expression in CD3 positive t cells.
For each sample, 10 ml of EDTA blood will be taken with the routine blood withdrawal. The blood sample will be used for the analysis of the T cell-specific mRNA PPARgamma expression. A total of 8 samples per patient will be examined. 4 blood samples from operative patients without infection and 2 blood samples from healthy donors will be taken and analyzed as control groups.
The T-cell subpopulations will be enriched by magnetic separation. From these enriched cell populations, we will isolate RNA to determine the level of PPARgamma mRNA expression. The quantification (ng/cell) of PPARgamma mRNA (ng/cell) will be measured by quantitative PCR using an established PPARgamma plasmid standard.

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

Secondary Outcome: The number of CD3 T cells and T cell subsets.
The number of CD3 T cells and T cell subsets will be determined by FACS analysis as cells/µl.
Secondary outcome: medical patient data.
In addition, the clinical parameters of the patients are determined at the respective time points after the diagnosis of the disease or the elective surgery. This includes blood pressure, body temperature, heart rate, and patients’ clinical condition as well as medication.

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • University Medical Center 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2019/02/07
  •   220
  •   Monocenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   85   Years
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

Healthy test persons: men and women between the ages of 18 and 85;

Spondylodiscitis: men and women between the ages of 18 and 85.
Patients with diagnosed spondylodiscitis;

Joint / prosthesis infection: men and women between the ages of 18 and 85.
Patients with diagnosed joint / prosthesis infection;

Surgical patients: men and women between the ages of 18 and 85.
Patients with elective surgery without evidence of infection.

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

Age < 18 years and > 85 years

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Orthopädische Universitätsklinik Friedrichsheim
    • Marienburgstraße 2
    • 60528  Frankfurt a.M.
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Orthopädische Universitätsklinik Friedrichsheim
    • Mr.  Dr.  Marco  Brenneis 
    • Marienburgstraße 2
    • 60528  Frankfurt a.M.
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Orthopädische Universitätsklinik Friedrichsheim
    • Mr.  Dr.  Marco  Brenneis 
    • Marienburgstraße 2
    • 60528  Frankfurt a.M.
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Orthopädische Universitätsklinik Friedrichsheim
    • Marienburgstraße 2
    • 60528  Frankfurt a.M.
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting ongoing
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  •   Prüfplan
end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.