Biomarker Signature and Musculoskeletal Ultrasound Profile in Rheumatoid Arthritis Patients

Study Overview
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Brief Summary
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The purpose of this study is to determine the kinetics of change in quantitative measures of joint inflammation by state of the art power Doppler vascular imaging and to identify biomarkers in biological samples (synovial biopsies, DNA, RNA, PBMC, serum, plasma, urine and stool samples) from parallel cohorts of RA patients undergoing different treatments. This will be achieved implementing MSUS assessments, standard laboratories techniques (such as ELISAs, gene profiling, transcriptome analysis etc.) and the novel CyTOF™ technology.

Official Title
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Biomarker Signature and Musculoskeletal Ultrasound Profile in Rheumatoid Arthritis Patients: a Pilot Observational Study

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Other: Musculoskeletal Ultrasound Imaging
* Other: Synovial biopsy
* Other: Biological samples collection
* Other: Questionnaires


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written confirmed diagnosis of Rheumatoid Arthritis as per ACR/EULAR 2010 criteria. If patient is on oral corticosteroids, dose must be stable for 6 weeks prior to baseline visit. Willingness and ability to comply with all the study procedures. Exclusion Criteria: Any systemic inflammation conditions (other than RA), connective tissue disease or chronic pain disorders that may interfere with the interpretation of the outcome data. Examples include psoriatic arthritis, reactive arthritis, gout, systemic lupus erythematosus (SLE), polymyalgia rheumatic and/or temporal arteritis, Lyme's disease, fibromyalgia and chronic fatigue syndromes. Major surgery planned within 8 weeks prior to screening or planned surgery throughout the study period. Treatment with any investigational agent ≤ 4 weeks prior to baseline (or 5 ≤ half-lives of the investigational drug, whichever is the longer). Intramuscular/intra-articular glucocorticoids for 6 weeks prior to baseline visit. Active infection. Septic arthritis within a native joint within the last 12 months. Sepsis of a prosthetic joint within 12 months or indefinitely if the joint remains in situ. Known HIV or hepatitis B/C infection. Latent TB infection unless they have completed adequate antibiotic prophylaxis. Malignancy (other than basal cell carcinoma) within the last 10 years. New York Heart Association (NYHA) grade 3 or 4 congestive cardiac failure. Demyelinating disease. Presence of a transplanted organ (with the exception of a corneal transplant > 3 months prior to screening). Known recent substance abuse (drug or alcohol).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Conventional synthetic DMARD naïve<br>Naive RA patients commencing Methotrexate and Hydroxychloroquine. Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires. | Other: Musculoskeletal Ultrasound Imaging<br>* B-mode and PD musculoskeletal ultrasound examination of selected joints.<br>Other: Synovial biopsy<br>* US guided synovial biopsy of an inflamed joint including wrists, MCP joints and knees.<br>Other: Biological samples collection<br>* Draw of research blood samples.<br>Other: Questionnaires<br>* Administration of validated patients' questionnaires.<br>|
| DMARD-IR: anti-TNF<br>Conventional synthetic DMARD inadequate responders commencing Anti-TNF Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires. | Other: Musculoskeletal Ultrasound Imaging<br>* B-mode and PD musculoskeletal ultrasound examination of selected joints.<br>Other: Synovial biopsy<br>* US guided synovial biopsy of an inflamed joint including wrists, MCP joints and knees.<br>Other: Biological samples collection<br>* Draw of research blood samples.<br>Other: Questionnaires<br>* Administration of validated patients' questionnaires.<br>|
| DMARD-IR: anti-IL6<br>Conventional synthetic DMARD inadequate responders commencing anti-IL6 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires. | Other: Musculoskeletal Ultrasound Imaging<br>* B-mode and PD musculoskeletal ultrasound examination of selected joints.<br>Other: Synovial biopsy<br>* US guided synovial biopsy of an inflamed joint including wrists, MCP joints and knees.<br>Other: Biological samples collection<br>* Draw of research blood samples.<br>Other: Questionnaires<br>* Administration of validated patients' questionnaires.<br>|
| DMARD-IR: anti-CTLA-4<br>Conventional synthetic DMARD inadequate responders commencing anti-CTLA-4 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires. | Other: Musculoskeletal Ultrasound Imaging<br>* B-mode and PD musculoskeletal ultrasound examination of selected joints.<br>Other: Synovial biopsy<br>* US guided synovial biopsy of an inflamed joint including wrists, MCP joints and knees.<br>Other: Biological samples collection<br>* Draw of research blood samples.<br>Other: Questionnaires<br>* Administration of validated patients' questionnaires.<br>|
| DMARD-IR: anti-CD20<br>Conventional synthetic DMARD inadequate responders commencing anti-CD20 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires. | Other: Musculoskeletal Ultrasound Imaging<br>* B-mode and PD musculoskeletal ultrasound examination of selected joints.<br>Other: Synovial biopsy<br>* US guided synovial biopsy of an inflamed joint including wrists, MCP joints and knees.<br>Other: Biological samples collection<br>* Draw of research blood samples.<br>Other: Questionnaires<br>* Administration of validated patients' questionnaires.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in synovial thickness and vascularity using a limited joint set musculoskeletal ultrasound examination in Rheumatoid Arthritis. |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the distribution of cell populations in biological samples from Rheumatoid Arthritis patients using CyTOF. |  | 3 years | 
| Changes in gene expression in biological samples from Rheumatoid Arthritis patients using gene profiling. |  | 3 years | 
| Changes in cytokines' concentration in biological samples from Rheumatoid Arthritis patients using ELISA and transcriptome analysis. |  | 3 years |