This trial has been completed.

Condition psoriatic arthritis
Sponsor University of Rochester
Collaborator University of Rochester Clinical and Translational Science Institute
Start date April 2015
End date December 2016
Trial size 68 participants
Trial identifier NCT02413749, RSRB 53086


Biologics such as anti-Tumor Necrosis Factor or TNF inhibitor (TNFi) for treatment of Psoriatic Arthritis (PsA) has greatly reduced bone damage. This collaborative study will provide insights into key mechanisms that underlie inflammatory arthritis and bone damage in psoriatic joints and will catalyze biomarker discovery, identifying early biologic responders to facilitate optimization of therapy.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Observational model case-control
Time perspective prospective
Individuals with psoriatic arthritis who are being treated standard of care with a stable DMARD or a biologic
Individuals with psoriatic arthritis who have had an inadequate response to a DMARD and are being treated standard of care with a biologic.

Primary Outcomes

Examination of molecular mechanisms underlying DC-STAMP and TRAF3 mediated osteoclastogenesis
time frame: week 0 to week 16

Secondary Outcomes

Assessment of DC-STAMP and TRAF3 as biologic predictor and treatment response markers in PsA
time frame: week 0 to week 16

Eligibility Criteria

All participants from 18 years up to 89 years old.

Inclusion Criteria: - All Subjects 1. Ability to provide written informed consent. 2. Subjects can be of either gender but must be at least 18 years old. 3. Subjects with PsA should fulfill CASPAR criteria - Longitudinal 1. Patients with active PsA starting standard of care biologic treatment. - Additional Blood Draw 1. Positive DC-STAMP signal at baseline - Cross-Sectional 1. Patients on stable DMARDS or biologics for more than 16 weeks. Exclusion Criteria: 1. Unable to donate blood because of poor venous access or intolerance of phlebotomy.

Additional Information

Official title DC-STAMP and TRAF3: Regulators of Osteoclastogenesis and Biomarkers in Psoriatic Arthritis
Principal investigator Christopher Ritchlin, MD/MPH
Description Psoriatic arthritis (PsA), an inflammatory joint disease associated with psoriasis (Ps), affects approximately 650,000 adults in the United States and is associated with increased morbidity and mortality. Bone damage develops in half these patients within the first two years of disease, often leaving them with impaired function and diminished quality of life. The emergence of anti-Tumor Necrosis Factor therapies (TNFi) has dramatically improved clinical response and slowed bone and cartilage degradation in PsA patients, however, only 50-60% of patients respond to these agents. To improve these outcomes, investigators must address two major gaps: a limited understanding of key events that underlie pathologic bone destruction and the absence of biomarkers to predict TNFi response and identify early TNFi responders to facilitate optimization of therapy. Bone damage is mediated by osteoclasts which arise from monocyte precursors in the blood. Osteoclast Precursors (OCPs) are dramatically increased in PsA, compared to controls, particularly in patients with bone damage on X-ray. The number of these circulation precursor cells dropped rapidly following treatment with TNFi. OCPs may serve as response biomarkers, but cost, time and high variability limit these assays. Osteoclast precursors express Dendritic Cell-Specific Transmembrane Protein (DC-STAMP), which is a seven-pass transmembrane protein required for fusion of monocytes to form osteoclasts and giant cells. Monocyte DC-STAMP levels dropped rapidly following treatment with TNFi. TNF receptor-associated factor 3 (TRAF3), an inhibitor of OC formation that correlates with extracellular TNF concentrations, is elevated in OCPs from PsA patients. These markers may predict TNFi treatment response. The goal of this study is to examine Psoriatic Arthritis patients prior to and after standard of care biologic treatment such as TNFi, while also examining DC-STAMP and TRAF3 expression in a cross-sectional analysis of patients on stable oral disease modifying agents (DMARDS) and in patients in low disease activity state on TNFi therapy. - Research Assays: The correlation between TRAF3 and DC-STAMP expression at the RNA and protein level may be examined for two baseline PsA patients by real-time PCR, flow cytometry and western after Chloroquine (CQ) blockade, which prevents TRAF3 degradation. Cells isolated from human PBMC may be sterile sorted prior to use in some in vitro assays. Sorted cells may be treated with CQ or MG132, a proteasome inhibitor, in OC-promoting media in time course and dose-response experiments and OCs counted to determine if DC-STAMP is degraded by the lysosome or proteasome. Peripheral Blood Mononucleated Cells (PBMCs) will be isolated from blood by centrifugation. These cells may be used for flow cytometry to analyze TRAF3 and DC-STAMP expression on monocytes along with OC quantification at baseline and/or approximately 4 months of treatment. DC-STAMP surface expression on PBMC from PsA patients correlated with the number of OCP in culture and the level of DC-STAMP on CD14+ monocytes declined significantly in PsA patients following TNFi. The decline in DC-sTAMP+CD14+ cells may serve as a measure of early response to TNFi.
Trial information was received from ClinicalTrials.gov and was last updated in March 2017.
Information provided to ClinicalTrials.gov by University of Rochester.