DC-STAMP: Regulators of Osteoclastogenesis and Response Marker in PsA

Study Purpose

The Investigators will examine if DC-STAMP can serve as an early marker of TNFi response in PsA. Identification of such a biomarker would permit rapid transition to a new agent, a major treatment advance. TNFi are the most effective therapies in PsA, however, methotrexate is frequently initiated early in the disease course based on its significantly lower cost. Unfortunately, the efficacy of MTX has not been supported in clinical trials and up to 40% of patients do not respond to TNFi therapy. Moreover, valid biomarkers to predict MTX or TNFi responses are currently unavailable. This study may also provide the first data on the comparative efficacy of MTX and TNFi using clinical, Ultrasound (US) and biomarker outcomes.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Yes
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Observational
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Ability to provide written informed consent.
  • - Subjects can be of either gender but must be at least 18 years old.
  • - Subjects with PsA should fulfill CASPAR criteria.
  • - Longitudinal: Patients with active PsA who will be starting a TNFi or non-biologic DMARD treatment (Subjects starting non-biologic DMARDS can have their blood drawn within the first few days of starting therapy).
  • - Additional Blood Draw: Positive DC-STAMP signal at baseline.
  • - Cross-Sectional: Patients on stable DMARDS or TNFi for more than 16 weeks.
  • - Healthy Subjects: Healthy controls should have no active systemic disorders or inflammatory conditions that would confound the results of the study.

Exclusion Criteria:

  • - Unable to donate blood because of poor venous access or intolerance of phlebotomy.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03011242
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Rochester
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Christopher Ritchlin, MD/MPH
Principal Investigator Affiliation Univerisity of Rochester
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherNIHNIH
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Psoriatic Arthritis
Study Website: View Trial Website
Additional Details

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 the 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, the investigators must address two major gaps: a limited understanding of key events that underlie pathologic bone destruction and the absence of biomarkers to predict biologic response and identify early biologic 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 circulating 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 DC-STAMP in Psoriatic Arthritis patients prior to and after starting standard of care treatment with a TNFi or non-biologic DMARD. We will also examine PsA patients with low disease activity on standard of care TNFi and PsA patients with low disease activity on standard of care non-biologic DMARDs will serve as controls. Three groups of subjects will be recruited. 1. Longitudinal: 30 subjects starting out on standard of care treatment with a TNFi or non-biologic DMARD will take part in the longitudinal section of the study. Subjects may be asked to have a blood draw at one additional visit before starting therapy for additional research assays if they are DC-STAMP positive. If the longitudinal subjects that return for an additional blood draw before starting medication have unusable sample data, they will be replaced by additional longitudinal subjects out of the 30 enrolled longitudinal participants to get sufficient data results of two subjects. The subjects with unusable data will continue in the longitudinal follow up study visits as intended. 2. Cross sectional: 36 patients will take part in the cross-sectional part of the study. 18 patients on stable non-biologic DMARDS and 18 patients on stable TNFi will be compared in the cross-sectional part. This population should be in good disease state such that their disease is controlled and treatment will not need to be changed. If longitudinal subjects fit the cross-sectional criteria and wish to participate, they will be re-consented for the cross-sectional part of the study. While 66 subjects will be studied in both the longitudinal and cross-sectional studies combined, up to 80 PsA subjects may be consented to allow for screen failures and to replace longitudinal subjects who withdraw or are lost to follow-up. 3. Assay Development: Up to 40 PsA or healthy subjects may be enrolled for blood draw for assay development and to test development of techniques for ultrasound comparison and scoring system validation.

Arms & Interventions

Arms

: Longitudinal Cohort: Psoriatic Arthritis

Individuals diagnosed with Psoriatic Arthritis starting standard of care treatment with a TNFi or non-biologic DMARD.

: Assay Development: Healthy or Psoriatic Arthritis

Individuals that are healthy or with a diagnosis of Psoriatic Arthritis will be enrolled for blood draws for assay development and/or for an ultrasound for development of techniques and scoring system validation.

: Cross-Sectional: Psoriatic Arthritis

Individuals diagnosed with Psoriatic Arthritis in good disease state on stable non-biologic DMARDS or on stable TNFi.

Interventions

Contact a Trial Team

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University of Rochester Medical Center, Rochester, New York

Status

Recruiting

Address

University of Rochester Medical Center

Rochester, New York, 14642

Site Contact

Amy Wielgosz, RN

[email protected]

585-275-1035

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