Trial document





This trial has been registered retrospectively.
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  DRKS00004838

Trial Description

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Title

Analyses of factors involved in bone remodeling and inflammation in Ankylosing Spondylitis (AS) patients undergoing etanercept therapy

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

In the study the concentrations of signaling molecules involved in inflammation and bone remodeling is analyzed in sera obtained from healthy individuals and from patients with ankylosing spondylitis during 12 weeks of treatment with etanercept (Enbrel). Patient samples are taken prior start of therapy and after 4 and 12 weeks of treatment. The study cohort will allow the determination of factors measured that are significantly altered either prior to therapy begin (when compared with healthy controls) or during the course of therapy with Etanercept (between the 3 treatment time points). This will provide insights into possible molecular mechanisms of action of etanercept therapy in ankylosing spondylitis with respect to markers of inflammation and bone remodeling.

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Brief Summary in Scientific Language

Ankylosing spondylitis (AS) is a systemic rheumatic disorder characterized by inflammation of the axial skeleton and large peripheral joints. It is a progressive seronegative arthritis in which chronic inflammation can lead to extensive new bone formation throughout the spine as well as to erosive bone destruction and the development of severe osteoporosis resulting in loss of mobility and an increased risk of bone fractures.
Tumor necrosis factor alpha (TNF-alpha) blockade has been shown to dramatically improve clinical outcome in AS patients, which suggests that this factor plays a central role in AS. However, the precise mechanisms through which this improvement occurs is poorly understood. Because TNF-alpha is a potent activator of NFkappaB, treatment with etanercept that leads to dysregulation of NFkappaB signaling is one possible mechanism that results in the positive clinical effects observed in AS patients undergoing this treatment.
Inflammation-induced dysregulation of osteoclast and osteoblast activity results in simultaneous pathologic bone loss and formation in inflamed regions, with the balance between bone loss and bone formation being controlled through a pathway in which NFkappaB plays a crucial role.
Receptor Activator of NFkappaB Ligand (RANKL) is expressed in activated T-cells as both a surface bound form and as a secreted form. This ligand binds to Receptor Activator of NFkappaB (RANK) on the cell membrane of osteoclasts that in turn leads to activation of NFkappaB in these cells. This results in osteoclast differentiation and ultimately in inflammatory bone resorbtion. The soluble receptor osteoprotegerin (OPG) acts as a decoy receptor for RANKL and interferes in the RANKL/RANK activation pathway inhibiting the activation of osteoclasts. As such the relative levels of RANKL and OPG have been shown to control bone modeling and bone loss.
The serum levels of RANKL and OPG, the inflammatory cytokines TNF-alpha and IL-6 are measured together with quantitation of the clinical markers of inflammation CRP and ESR. Clinical evaluation of the patients is performed using the Bath ankylosing spondylitis disease activity index BASDAI.
The determination of these parameters in AS patients undergoing therapy with etanercept when compared with healthy control individuals will yield insights into possible connection between bone remodeling factors and inflammation.

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Organizational Data

  •   DRKS00004838
  •   2013/03/20
  •   [---]*
  •   yes
  •   Approved
  •   A 04/2008, Ethik-Kommission an der Medizinischen Fakultät der Universität Rostock
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Secondary IDs

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Health Condition or Problem studied

  •   M45.00 -  [generalization M45: Ankylosing spondylitis]
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Interventions/Observational Groups

  •   Patients with ankylosing spondylitis, weekly etanercept (Enbrel) 50mg s.c. over 12 weeks. Prior to the start of therapy and after 4 and 12 weeks of treatment blood samples will be taken. The disease activity (BASDAI) will be determined through use of a questionnaire at the 0 and 12 weeks time points.
  •   Healthy individuals. A blood sample is taken at the start of the study.
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Characteristics

  •   Non-interventional
  •   Other
  •   Non-randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Other
  •   Basic research/physiological study
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

Determination of erythrocyte sedimentation rate (ESR, lab results) prior to the start of therapy and after 4 and 12 weeks of treatment. Calculation of disease activity (BASDAI) through the evaluation of questionnaires filled out prior to the start of therapy and after 12 weeks of treatment.

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Secondary Outcome

[---]*

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
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Recruitment

  •   Actual
  •   2008/03/04
  •   56
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

AS patients meeting the criteria of the European Spondyloathropathy Study Group and eligible for treatment with Etanercept and healthy control individuals

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Exclusion Criteria

Not meeting the inclusion criteria healthy control individuals demonstrating obvious signs of inflammation

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Rheumazentrum Prof. Dr. med. G. Neeck
    • Mr.  Prof. Dr. med.  Gunther  Neeck 
    • Goethestraße 40
    • 18209  Bad Doberan
    • Germany
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    • Rheumazentrum Prof. Dr. med. G. Neeck
    • Mr.  Prof. Dr. med.  Gunther  Neeck 
    • Goethestraße 40
    • 18209  Bad Doberan
    • Germany
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    • Rheumazentrum Prof. Dr. med. G. Neeck
    • Mr.  Prof. Dr. med.  Gunther  Neeck 
    • Goethestraße 40
    • 18209  Bad Doberan
    • Germany
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Sources of Monetary or Material Support

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    • Wyeth Pharma GmbH
    • Wienburgstraße 207
    • 48159  Münster
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2009/03/23
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.