Biomarker Signature and Musculoskeletal Ultrasound Profile in Rheumatoid Arthritis Patients

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Other: Musculoskeletal Ultrasound Imaging; Other: Synovial biopsy; Other: Biological samples collection; Other: Questionnaires

• Registration Number: NCT02476084
• Lead Sponsor: University of Oxford

Brief Summary

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2014-10-13
• Study First Submitted: 2015-05-19
• Study First Submitted QC: 2015-06-16
• Study First Posted: 2015-06-19
• Status Verified: 2020-10
• Primary Completion: 2021-10-01
• Study Completion: 2021-10-01
• Last Update Submitted: 2022-05-19
• Last Update Posted: 2022-05-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 43

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.

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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).

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Conventional synthetic DMARD naïve	Synovial biopsy	Naive RA patients commencing Methotrexate and Hydroxychloroquine. Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
DMARD-IR: anti-TNF	Biological samples collection	Conventional synthetic DMARD inadequate responders commencing Anti-TNF Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
DMARD-IR: anti-TNF	Musculoskeletal Ultrasound Imaging	Conventional synthetic DMARD inadequate responders commencing Anti-TNF Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
DMARD-IR: anti-TNF	Synovial biopsy	Conventional synthetic DMARD inadequate responders commencing Anti-TNF Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
DMARD-IR: anti-TNF	Questionnaires	Conventional synthetic DMARD inadequate responders commencing Anti-TNF Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
Conventional synthetic DMARD naïve	Musculoskeletal Ultrasound Imaging	Naive RA patients commencing Methotrexate and Hydroxychloroquine. Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
Conventional synthetic DMARD naïve	Biological samples collection	Naive RA patients commencing Methotrexate and Hydroxychloroquine. Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
Conventional synthetic DMARD naïve	Questionnaires	Naive RA patients commencing Methotrexate and Hydroxychloroquine. Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
DMARD-IR: anti-IL6	Musculoskeletal Ultrasound Imaging	Conventional synthetic DMARD inadequate responders commencing anti-IL6 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
DMARD-IR: anti-IL6	Biological samples collection	Conventional synthetic DMARD inadequate responders commencing anti-IL6 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
DMARD-IR: anti-CTLA-4	Musculoskeletal Ultrasound Imaging	Conventional synthetic DMARD inadequate responders commencing anti-CTLA-4 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
DMARD-IR: anti-CTLA-4	Synovial biopsy	Conventional synthetic DMARD inadequate responders commencing anti-CTLA-4 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
DMARD-IR: anti-CTLA-4	Questionnaires	Conventional synthetic DMARD inadequate responders commencing anti-CTLA-4 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
DMARD-IR: anti-CD20	Musculoskeletal Ultrasound Imaging	Conventional synthetic DMARD inadequate responders commencing anti-CD20 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
DMARD-IR: anti-IL6	Synovial biopsy	Conventional synthetic DMARD inadequate responders commencing anti-IL6 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
DMARD-IR: anti-IL6	Questionnaires	Conventional synthetic DMARD inadequate responders commencing anti-IL6 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
DMARD-IR: anti-CTLA-4	Biological samples collection	Conventional synthetic DMARD inadequate responders commencing anti-CTLA-4 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
DMARD-IR: anti-CD20	Synovial biopsy	Conventional synthetic DMARD inadequate responders commencing anti-CD20 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
DMARD-IR: anti-CD20	Biological samples collection	Conventional synthetic DMARD inadequate responders commencing anti-CD20 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.
DMARD-IR: anti-CD20	Questionnaires	Conventional synthetic DMARD inadequate responders commencing anti-CD20 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.

Primary Outcome Measures

Name	Time	Method
Changes in synovial thickness and vascularity using a limited joint set musculoskeletal ultrasound examination in Rheumatoid Arthritis.	3 years

Secondary Outcome Measures

Name	Time	Method
Changes in gene expression in biological samples from Rheumatoid Arthritis patients using gene profiling.	3 years
Changes in the distribution of cell populations in biological samples from Rheumatoid Arthritis patients using CyTOF.	3 years
Changes in cytokines' concentration in biological samples from Rheumatoid Arthritis patients using ELISA and transcriptome analysis.	3 years

Trial Locations

Locations (1)

Nuffield Orthopaedic Centre; 🇬🇧 Oxford, United Kingdom