Trial document




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  DRKS00003536

Trial Description

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Title

Impact of Intra-articular Infections on chondral layers (Triple-I)

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Trial Acronym

Triple-I

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URL of the Trial

[---]*

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Brief Summary in Lay Language

An infection of a joint causes a damage of the cartilage, the beginning of osteoarthritis. This disease is not reversible and may often only be treated by an arthroplasty. Aim of this study is the investigation of the molecular mechanisms that cause the changes in cartilage biology following an infection. For this reason, effusions of infected joints (knee, shoulder, ankle and hip) are collected and analyzed. Additionally, scores for life quality and joint specific scores are evaluated.

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Brief Summary in Scientific Language

In joint infections, the chondrocyte response is characterized by enhanced cell proliferation and cell death, matrix degradation, and, as part of the repair processes following acute inflammation, new matrix synthesis. Cytokines are important stimuli of this chondrocyte activation response, and trigger joint inflammation that can cause cartilage injury. The early part of the acute-phase response involves the local action and production of cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF) and IL-6. IL-1 and TNFa induce neutrophil and macrophage recruitment and activation1, IL-6 plays a dual role in connective tissue pathology, reducing proteoglycan loss in the acute phase and enhancing osteophyte formation in the chronic phase. The presence of cytokines in cartilage is associated with abnormal extracellular matrix remodeling and loss, therefore defining them as a class of targets for therapeutic interventions. Insight into intracellular signaling mechanisms that are activated by cytokines may provide the basis for pharmacologic interventions that promote cartilage repair. p38 activation and NF-κB recruitment play both important roles in chondrocyte differentiation and inflammation. Inflammatory reactions after cartilage regenerating surgical interventions against scaffold materials and serum components also lead to the production of cytokines such as IL-1 that may inhibit cartilage tissue formation in autologous transplant models. The goal of this study is to evaluate the influence of inflammatory mediators and inflammation-dependent growth factors on chondrocyte proliferation, differentiation, matrix production, intracellular signaling, and cell function in acute and chronic joint infections. The proposed inflammatory models reflect mechanisms in acute infection by using the cell wall component of gram negative bacteria LPS (lipopolsaccharide) that strongly induces inflammatory reactions in a bride variety of tissues, or using a direct incubation with a major player in acute inflammatory response as TNFa or IL-1. Data gained in in vitro experiments may be matched with in vivo data obtained from an analysis of lavage fluids of infected knee joints. This provides the unique opportunity to correlate data of an experimental model with data of real patients in terms of cytokine expression. Additionally, these results can be compared and correlated with clinical scores of patients after an infection. Furthermore, the effect of drugs as Nonsteroidal Antiinflammatory Drugs (NSAID), acting as COX-inhibitors, on both in vivo and in vitro cellular response will be investigated.
Effusions of infected joints (knee, shoulder, ankle and hip) are collected and analyzed. Additionally, scores for life quality and joint specific scores are evaluated. Clinical data is supplemented by in vitro-models.

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Organizational Data

  •   DRKS00003536
  •   2012/02/03
  •   [---]*
  •   yes
  •   Approved
  •   50/11, Ethik-Kommission der Albert-Ludwigs-Universität Freiburg
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Secondary IDs

  •   U1111-1127-5668 
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Health Condition or Problem studied

  •   M00.96 -  [generalization M00.9: Pyogenic arthritis, unspecified]
  •   M00.91 -  [generalization M00.9: Pyogenic arthritis, unspecified]
  •   M00.95 -  [generalization M00.9: Pyogenic arthritis, unspecified]
  •   M00.97 -  [generalization M00.9: Pyogenic arthritis, unspecified]
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Interventions/Observational Groups

  •   Included are patients with joint infections in knee, shoulder, ankle or hip. During the treatment lavage fluids of the joints are collected. The samples are analyzed for the presence of cytokines that are involved in cartilage metabolism. Additionally, clinical data of life quality and specific joint function are evaluated before the infection and a year later.
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Characteristics

  •   Non-interventional
  •   Observational study
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Prognosis
  •   Single (group)
  •   N/A
  •   N/A
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Primary Outcome

Quality of life befor infection and 1 year later: SF12, Eurocol EQ5D

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Secondary Outcome

Additionally, after 1 year the following specific joint scores are evaluated:
Knee: Lysholm, IKDC
Shoulder: DASH
Ankle: AOFAS, FFI
Hip: WOMAC
These scores are compared with the status before the infection.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • [---]*
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Recruitment

  •   Planned
  •   2012/01/31
  •   100
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   81   Years
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Additional Inclusion Criteria

1. Diagnosis of a joint infection in knee, shoulder, ankle or hip
2. Performance of a puncture, an arthroscopy or of an open revision of the affected joint for diagnostic or therapeutic reasons
3. age of at least 18 years
4. Informed consent

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Exclusion Criteria

1. alcohol- or drug abuse (except smoking)
2. inability of cognitive comprehension of the study and the associated conditions

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Addresses

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Sources of Monetary or Material Support

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    • Bundesministerium für Bildung und Forschung Dienstsitz Berlin
    • Friedrichstraße 130 B
    • 10117  Berlin
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2013/12/31
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Trial Publications, Results and other Documents

  •   Prospective Clinical Trial for Septic Arthritis: Cartilage Degradation and Inflammation Are Associated with Upregulation of Cartilage Metabolites. Schmal H, Bernstein A, Feucht MJ, Erdle B, Pestka JM, Pham TM, Kubosch EJ. Mediators Inflamm. 2016;2016:5491971.
  •   Clinical Trial and In Vitro Study for the Role of Cartilage and Synovia in Acute Articular Infection. Langenmair ER, Kubosch EJ, Salzmann GM, Beck S, Schmal H. Mediators Inflamm. 2015;2015:430324.
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* This entry means the parameter is not applicable or has not been set.