Serum, Cellular and Imaging Markers of Arthritis in Psoriasis Patients (RRF)
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|ClinicalTrials.gov Identifier: NCT02413801|
Recruitment Status : Active, not recruiting
First Posted : April 10, 2015
Last Update Posted : February 15, 2019
|Condition or disease|
Our long-term goals are to: 1) develop arthritis biomarkers in psoriasis patients that will facilitate early treatment interventions; and, 2) identify new therapeutic targets in PsA through better understanding of the underlying molecular pathogenesis. PsA, an inflammatory arthritis associated with psoriasis, affects approximately 650,000 adults in the United States and is associated with increased morbidity and mortality. Joint inflammation and damage arise within the first 2 years of disease in 50% of patients who manifest bone erosions and joint space narrowing on plain x-rays. The advent of Tumor Necrosis Factor antagonists (TNFi) for treatment of PsA has dramatically improved clinical response and slowed bone and cartilage degradation. Nevertheless, up to 45% of patients do not meet primary endpoints in clinical trials, which underscores the need for new therapeutic options.
Another approach to improve treatment response is early PsA diagnosis, and recent data indicate that treatment soon after disease onset can improve outcomes. Relevant to the potential for early intervention and prevention, psoriatic skin plaques typically precede PsA by 10 years. Moreover, a significant percentage of these psoriasis patients have subclinical musculoskeletal imaging findings. These findings provide an unparalleled opportunity for early intervention that could potentially limit or halt joint inflammation and damage. Regrettably, despite the obvious advantages of early diagnosis and treatment, this goal remains elusive because the clinical significance of imaging abnormalities in psoriasis remains unknown. Furthermore, investigators have limited understanding of the mechanisms that underlie the transition from psoriasis to PsA, and investigators lack the disease specific biomarkers necessary to identify psoriasis patients with new onset arthritis or sub-clinical disease. Lastly, up to a third of psoriasis patients with moderate to severe skin disease report they are undertreated and many are on topical agents unlikely to have a significant effect on subclinical or clinically apparent joint inflammation.
Up to 150 subjects will be consented and studied in this cross-sectional study - 125 subjects with Psoriasis (Ps) and 25 Healthy controls. Power Doppler Ultrasound (PDUS) in joints and entheses will be analyzed to find at least 35 subjects with positive US findings defined as synovitis, effusion, joint erosions, or increased vascularity otherwise known as a signal. Up to 50 Ps patients with positive PDUS results will be followed prospectively and contacted at intervals to update medication history indefinitely. Ps patients will be asked for a follow up PDUS 4 months post start of biologic, DMARD therapy or phototherapy if the patient decides to go on such therapies to study longitudinally.
Up to 30 bone marrow aspirations on healthy and PDUS positive Psoriasis subjects will be performed. A bone marrow aspiration post start of biologic or DMARD standard of care therapy will be assessed as well.
Research assays: serum will be used to measure biomarker 14-3-3η levels, which may be analyzed by an external company. Peripheral blood will be used to measure the frequency of DC-STAMP+ cells (CD14+DC-STAMP+ CD4+DCSTAMP+DC-STAMP+IL-17+). Using multichromatic flow cytometry, we will measure DC-STAMP expression on peripheral blood cells and on bone marrow cells. To determine if elevated BM DC-STAMP expression by stromal cells, T cells and/or monocytes promotes OC formation, co-cultures of bone marrow stromal and hematopoietic cells with peripheral blood cells will be analyzed for OCPs.
|Study Type :||Observational|
|Actual Enrollment :||103 participants|
|Official Title:||Serum, Cellular and Imaging Markers of Arthritis in Psoriasis Patients|
|Actual Study Start Date :||March 19, 2015|
|Estimated Primary Completion Date :||October 2019|
|Estimated Study Completion Date :||October 2019|
Individuals with psoriasis
Individuals that are healthy
- Correlation of abnormal ultrasound signals with peripheral blood in subclinical PsA [ Time Frame: Week 0 ]To examine if subclinical PsA, as measured by abnormal ultrasound signals, correlate with peripheral blood cellular and serologic biomarkers of inflammation and joint damage. Power Doppler Ultrasound (PDUS) signals in joints and entheses of approximately 125 Ps pts in order to identify at least 35 pts with subclinical PsA (and 25 healthy controls). Investigators will compare both the frequency of DC-STAMP+ cells (CD14+DCSTAMP+ CD4+DC-STAMP+ DC-STAMP+IL-17+) and serum biomarker 14-3-3η levels between the Ps pts with subclinical PsA (PDUS+), up to 50 Ps pts without evidence of subclinical PsA (PDUS-), and controls.
- To understand if systemic therapies for Ps can reduce subclinical joint inflammation. [ Time Frame: Week 0 to week 16 ]Investigators will monitor the change in PDUS signals and PB biomarkers in at least 35 subclinical PsA pts identified from baseline to month 4 following Phototherapy, DMARD or Biologic therapy.
- To examine if DC-STAMP expression on BM cells is associated with subclinical PsA and increased OC formation in psoriasis. [ Time Frame: Week 0 to week 16 ]Investigators will analyze PB and BM DC-STAMP expression in PDUS+ pts evaluated at baseline and at 4 months post standard of care treatment. Then, to determine if elevated BM DC-STAMP expression by stromal cells, T cells and/or monocytes promotes OC formation, co-cultures of BM stromal and hematopoietic cells with PB cells will be analyzed for OCPs.
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02413801
|United States, New York|
|University of Rochester|
|Rochester, New York, United States, 14642|
|Principal Investigator:||Christopher Ritchlin, MD/MPH||University of Rochester|