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National Psoriasis Foundation - Dendritic Cell-Specific Transmembrane Protein (DC-Stamp) Biomarker Study

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01123265
First Posted: May 14, 2010
Last Update Posted: September 21, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Psoriasis Foundation
Information provided by (Responsible Party):
Christopher Ritchlin, University of Rochester
May 11, 2010
May 14, 2010
September 21, 2015
June 2010
June 2014   (Final data collection date for primary outcome measure)
  • Analysis of T cell subset and dendritic cell (DC) subset for DC-STAMP expression [ Time Frame: Week 0 (Baseline) ]
    Determine whether DC-STAMP+ cells belong to the Th17 subset and also analyze the DC subsets for DC-STAMP expression.
  • Analysis of T cell subset and DC subset for DC-STAMP expression [ Time Frame: Week 16 ]
    Determine whether DC-STAMP+ cells belong to the Th17 subset and also analyze the DC subsets for DC-STAMP expression.
  • DC-STAMP as a marker of disease severity in PsA [ Time Frame: Week 0 (Baseline) ]
    Baseline measurement of DC-STAMP expression will be collected in order to assist in determining whether it is associated with more severe features of PsA. DC-STAMP expression will be correlated with clinical variables of arthritis and skin disease, CRP and x-ray damage.
  • DC-STAMP as a marker of disease severity in PsA [ Time Frame: Week 16 ]
    Measurement of DC-STAMP expression will be collected in order to assist in determining whether it is associated with more severe features of PsA. DC-STAMP expression will be correlated with clinical variables of arthritis and skin disease, CRP and x-ray damage.
  • DC-STAMP as a biomarker of treatment response in PsA [ Time Frame: Week 0 (Baseline) ]
    A baseline measurement of DC-STAMP as a response marker to treatment will be collected. Ten subjects will receive methotrexate and ten will receive anti-TNF therapy. The correlation between DC-STAMP variables (percentage of 1A2+ divided by 1A2 - cells X 100) and the variables detailed in Aim 2 will be analyzed in these 2 treatment groups at 2 different time points.
  • DC-STAMP as a biomarker of treatment response in PsA [ Time Frame: Week 16 ]
    A measurement of DC-STAMP as a response marker to treatment will be collected. Ten subjects received methotrexate and ten received anti-TNF therapy. The correlation between DC-STAMP variables (percentage of 1A2+ divided by 1A2 - cells X 100) and the variables detailed in Aim 2 will be analyzed in these 2 treatment groups at 2 different time points.
  • Analysis of T cell subset and DC subset for DC-STAMP expression [ Time Frame: Week 0 (Baseline) ]
    Determine whether DC-STAMP+ cells belong to the Th17 subset and also analyze the DC subsets for DC-STAMP expression.
  • Analysis of T cell subset and DC subset for DC-STAMP expression [ Time Frame: Week 16 ]
    Determine whether DC-STAMP+ cells belong to the Th17 subset and also analyze the DC subsets for DC-STAMP expression.
  • DC-STAMP as a marker of disease severity in PsA [ Time Frame: Week 0 (Baseline) ]
    Baseline measurement of DC-STAMP expression will be collected in order to assist in determining whether it is associated with more severe features of PsA. DC-STAMP expression will be correlated with clinical variables of arthritis and skin disease, CRP and x-ray damage.
  • DC-STAMP as a marker of disease severity in PsA [ Time Frame: Week 16 ]
    Measurement of DC-STAMP expression will be collected in order to assist in determining whether it is associated with more severe features of PsA. DC-STAMP expression will be correlated with clinical variables of arthritis and skin disease, CRP and x-ray damage.
  • DC-STAMP as a biomarker of treatment response in PsA [ Time Frame: Week 0 (Baseline) ]
    A baseline measurement of DC-STAMP as a response marker to treatment will be collected. Ten subjects will receive methotrexate and ten will receive anti-TNF therapy. The correlation between DC-STAMP variables (percentage of 1A2+ divided by 1A2 - cells X 100) and the variables detailed in Aim 2 will be analyzed in these 2 treatment groups at 2 different time points.
  • DC-STAMP as a biomarker of treatment response in PsA [ Time Frame: Week 16 ]
    A measurement of DC-STAMP as a response marker to treatment will be collected. Ten subjects received methotrexate and ten received anti-TNF therapy. The correlation between DC-STAMP variables (percentage of 1A2+ divided by 1A2 - cells X 100) and the variables detailed in Aim 2 will be analyzed in these 2 treatment groups at 2 different time points.
Complete list of historical versions of study NCT01123265 on ClinicalTrials.gov Archive Site
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National Psoriasis Foundation - Dendritic Cell-Specific Transmembrane Protein (DC-Stamp) Biomarker Study
Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) as a Severity and Response Biomarker in Psoriatic Arthritis
The purpose of this study is to determine whether DC-STAMP, a protein on the surface of osteoclast precursors (OCPs), can be used as a biologic marker in Psoriatic Arthritis (PsA). With this marker the investigators hope to learn more about how OCPs develop as well as find out if DC-STAMP predicts PsA severity and how well treatment works in PsA.

Psoriatic Arthritis (PsA), a phenotypically heterogeneous disorder, is characterized by joint damage observed in over half of the patients with early disease. While anti-tumor necrosis factor (TNF) agents have greatly improved signs and symptoms and lessened joint damage, the fact that only a fraction of patients achieve complete remission underscores the tremendous unmet need for this population. To date, a biomarker that can stratify patients by severity and can serve as a leading indicator of treatment response has not been identified.

Our laboratory demonstrated that circulating osteoclast precursors (OCP) are elevated in PsA patients. OCP decline rapidly following anti-TNF therapy and levels are higher in subjects with erosive arthritis compared to those with no x-ray changes. The OCP are derived from CD14+ monocytes and the assay entails culture techniques that are costly, expensive and labor intensive. We developed an antibody (1A2) to Dendritic Cell Specific Transmembrane Protein (DC-STAMP), a potential marker of the OCP population, for analysis by flow cytometry. We found that: 1) the level of monocyte DC-STAMP expression correlated with in vitro osteoclast formation; 2) DC-STAMP expression is significantly elevated in PBMC from PsA subjects compared to controls; 3) TNF dramatically upregulated the expression of DC-STAMP in vitro; 4) DC-STAMP surface expression declined following anti-TNF therapy; 5) subsets of CD3+ cells also express DC-STAMP on the cell membrane. Based on these preliminary data, three hypotheses are proposed:

  1. DC-STAMP+ CD3+ T cells belong to the Th17 subset which facilitates OC generation;
  2. DC-STAMP is a marker of disease severity in PsA;
  3. DC-STAMP is a biomarker of treatment response in PsA.

We propose three Specific Aims to test these hypotheses.

Aim 1 To examine whether DC-STAMP+CD3+ cells belong to the Th17 cell subset, PBMC will be stained with Th17-specific antibodies in PsA subjects with elevated DC-STAMP expression. We will also examine the role of T cells in osteoclastogenesis directly by co-culture experiments and we will use monocyte cultures without added lymphocytes as controls. The expression of DC-STAMP on circulating dendritic cells will be examined ex vivo with 11-color flow cytometry.

Aim 2 To determine if increased DC-STAMP expression is associated with more severe features of PsA, DC-STAMP expression in 40 PsA subjects will be determined and correlated with clinical variables of arthritis and skin disease, CRP and x-ray damage.

Aim 3 To examine if DC-STAMP is a response marker to anti-TNF treatment, we will recruit 20 PsA patients in Aim 2 with elevated DC-STAMP expression and divide them into 2 groups. Ten subjects will receive methotrexate, and ten will receive anti-TNF therapy. The correlation between DC-STAMP variables (percentage of 1A2+ divided by 1A2 - cells X 100) and the variables detailed in Aim 2 will be analyzed in these 2 treatment groups at 2 different time points.

Observational
Observational Model: Case Control
Time Perspective: Prospective
Not Provided
Not Provided
Non-Probability Sample
Male and female population that are 18 years old and older.
Psoriatic Arthritis
  • Drug: Methotrexate
    Subjects will start Methotrexate which will be escalated from 7.5 mg weekly to 15 mg/weekly over a 3 week period.
  • Drug: Anti-TNF
    Anti-TNF to be administered per standard of care within the practice.
  • Anti-TNF
    Intervention: Drug: Anti-TNF
  • Methotrexate
    Intervention: Drug: Methotrexate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
22
June 2014
June 2014   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Subject must be >18 years old
  2. Subject must have >3 tender and swollen joints
  3. Subject must have must have a target lesion of greater than 3 cm in diameter
  4. Subjects who meet the the ClASsification of Psoriatic ARthritis (CASPAR) criteria for PsA
  5. Subjects must have a DC-STAMP pattern III or IV

Exclusion Criteria:

  1. Subjects with active inflammatory synovitis, dactylitis, enthesitis, osteoarthritis, axial disease, Subjects with a SLE, Sjogren's syndrome, scleroderma or inflammatory muscle disease
  2. Subjects with an active malignancy
  3. Subjects currently on biologic agents (anti-TNF agents, anti-T or B cells agents) and/or disease-modifying antirheumatic drugs (DMARDs) (methotrexate, leflunomide, hydroxychloroquine, azulfidine, cyclosporine, azathioprine)
  4. Subjects who have been off DMARDs or biologics for less than 3 months
  5. Subjects judged ineligible at the discretion of the PI
  6. Subjects with a history of crystalline arthritis (gout, pseudogout)
  7. Subject pregnancy or breast feeding
  8. History of recurrent infections - AIM 3 Specific
  9. Demyelinating disorders - AIM 3 Specific
  10. Prior non-responsiveness to TNFi - AIM 3 Specific
  11. Subjects who have a BMI >30 - AIM 3 Specific MTX arm
  12. Subjects who have a history of type II diabetes - AIM 3 Specific MTX arm
  13. Subjects with a history of substance abuse including alcohol - AIM 3 Specific MTX arm
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01123265
RSRB - 32368
No
Not Provided
Not Provided
Christopher Ritchlin, University of Rochester
University of Rochester
National Psoriasis Foundation
Principal Investigator: Christopher Ritchlin, MD / MPH University of Rochester
University of Rochester
September 2015