Overview

This trial is active, not recruiting.

Condition psoriasis
Sponsor University of Rochester
Collaborator Rheumatology Research Foundation
Start date March 2015
End date October 2018
Trial size 103 participants
Trial identifier NCT02413801, RSRB 53131

Summary

The events that underlie the conversion from Psoriasis to Psoriatic Arthritis (PsA) are not well understood. This conversion occurs 30% of the time within the first 10 years of psoriasis diagnosis. PsA patients have about a 50% chance of developing joint damage within the first 2 years of disease. A biomarker that identifies subclinical joint inflammation in psoriasis patients would allow for a diagnostic tool to allow for earlier intervention in psoriasis patients and provide a better understanding of the underlying molecular pathogenesis that may lead to development of new therapeutic targets in PsA.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Observational model case control
Time perspective prospective
Arm
Individuals with psoriasis
Individuals that are healthy

Primary Outcomes

Measure
Correlation of abnormal ultrasound signals with peripheral blood in subclinical PsA
time frame: Week 0
To understand if systemic therapies for Ps can reduce subclinical joint inflammation.
time frame: Week 0 to week 16
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

Eligibility Criteria

Male or female participants from 18 years up to 89 years old.

Inclusion Criteria: - All Subjects 1. Ability to provide written informed consent 2. Subjects must be 18 years old or older - Psoriasis Subjects 1. Patients with self-diagnosed Psoriasis. These subjects may present with thick, scaly, silvery and/or red skin, without ever having been diagnosed by a dermatologist: - Starting either a DMARD or biologic standard of care for their psoriasis OR - Currently started taking a DMARD within the last two weeks of study visit procedures OR - Currently not using a DMARD or biologic treatment, subjects may be using topical creams or UV therapy 2. Willing to be studied longitudinally with a 4 month follow-up blood draw and PDUS if initial PDUS demonstrates positive findings. - Bone Marrow Aspiration: 1. Willing to undergo procedure. 2. Psoriasis: positive findings on Power Doppler Ultra Sound (PDUS+) such as joint erosion, effusion, synovitis or increased vascularity, otherwise known as a signal. Exclusion Criteria: - All Subjects 1. Unable to donate blood because of poor venous access or intolerance of phlebotomy. 2. Chronic pain syndrome, autoimmune or active inflammatory conditions other than the conditions being studied. (i.e., chronic infection with hepatitis B or hepatitis C, inflammatory arthritis, etc) which in the investigator's opinion may confound the study results. - Healthy subjects: 1. Musculoskeletal conditions such as joint pains or swelling, fracture, tendonitis or trauma in the past 3 months, gout, or any arthritis which in the investigator's opinion may confound the study results. 2. Illness in the last month which in the investigator's opinion may confound the study results. 3. Taking systemic steroids or immunosuppressants - Psoriasis Subjects: 1. Evidence of inflammatory arthritis. 2. Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire score greater than or equal to 47. 3. Meet CASPAR criteria for PsA. - Bone Marrow Aspiration: 1. Side effect to local anesthetics such as lidocaine or novocain. 2. Bleeding disorders or conditions requiring treatment with, NSAID, aspirin, anti-coagulants or anti-platelet agent, unless a physician investigator determines it to be safe to hold these agents for 2 weeks. 3. Known thrombocytopenia (< 100,000) or clinically significant PT or PTT outside the normal range. 4. Pregnant women should not participate; Pregnancy tests will not be performed.

Additional Information

Official title Serum, Cellular and Imaging Markers of Arthritis in Psoriasis Patients
Principal investigator Christopher Ritchlin, MD/MPH
Description 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 asked for a follow up PDUS 4 months later 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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by University of Rochester.