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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2012 by University of Rochester
Sponsor:
Collaborator:
National Psoriasis Foundation
Information provided by (Responsible Party):
Christopher Ritchlin, University of Rochester
ClinicalTrials.gov Identifier:
NCT01123265
First received: May 11, 2010
Last updated: July 27, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Psoriatic Arthritis
Drug: Methotrexate
Drug: Anti-TNF
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) as a Severity and Response Biomarker in Psoriatic Arthritis

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • Analysis of T cell subset and dendritic cell (DC) subset for DC-STAMP expression [ Time Frame: Week 0 (Baseline) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 44
Study Start Date: June 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Anti-TNF Drug: Anti-TNF
Anti-TNF to be administered per standard of care within the practice.
Active Comparator: Methotrexate Drug: Methotrexate
Subjects will start Methotrexate which will be escalated from 7.5 mg weekly to 15 mg/weekly over a 3 week period.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01123265

Contacts
Contact: Rick A Barrett, MT / MBA 585-275-1647 rick_barrett@urmc.rochester.edu

Locations
United States, New York
University of Rochester Recruiting
Rochester, New York, United States, 14642
Sponsors and Collaborators
University of Rochester
National Psoriasis Foundation
Investigators
Principal Investigator: Christopher Ritchlin, MD / MPH University of Rochester
  More Information

No publications provided

Responsible Party: Christopher Ritchlin, M.D., M.P.H.; Professor of Medicine Allergy, Immunology & Rheumatology Division, University of Rochester
ClinicalTrials.gov Identifier: NCT01123265     History of Changes
Other Study ID Numbers: RSRB - 32368
Study First Received: May 11, 2010
Last Updated: July 27, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Rochester:
PsA
methotrexate
Anti-TNF
TNF
DC-Stamp

Additional relevant MeSH terms:
Arthritis, Psoriatic
Arthritis
Bone Diseases
Joint Diseases
Musculoskeletal Diseases
Psoriasis
Skin Diseases
Skin Diseases, Papulosquamous
Spinal Diseases
Spondylarthritis
Spondylarthropathies
Spondylitis
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014