Biomarker Signature and Musculoskeletal Ultrasound Profile in Rheumatoid Arthritis Patients

NCT02476084 | Completed DMC

• 1 other identifier: 149600
• Study Type: observational
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Changes in synovial thickness and vascularity using a limited joint set musculoskeletal ultrasound examination in Rheumatoid Arthritis.

  3 years

Secondary Outcomes (3)

• 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

Study Arms (5)

Conventional synthetic DMARD naïve

Naive RA patients commencing Methotrexate and Hydroxychloroquine. Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.

Other: Musculoskeletal Ultrasound Imaging; Other: Synovial biopsy; Other: Biological samples collection; Other: Questionnaires

DMARD-IR: anti-TNF

Conventional synthetic DMARD inadequate responders commencing Anti-TNF Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.

Other: Musculoskeletal Ultrasound Imaging; Other: Synovial biopsy; Other: Biological samples collection; Other: Questionnaires

DMARD-IR: anti-IL6

Conventional synthetic DMARD inadequate responders commencing anti-IL6 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.

Other: Musculoskeletal Ultrasound Imaging; Other: Synovial biopsy; Other: Biological samples collection; Other: Questionnaires

DMARD-IR: anti-CTLA-4

Conventional synthetic DMARD inadequate responders commencing anti-CTLA-4 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.

Other: Musculoskeletal Ultrasound Imaging; Other: Synovial biopsy; Other: Biological samples collection; Other: Questionnaires

DMARD-IR: anti-CD20

Conventional synthetic DMARD inadequate responders commencing anti-CD20 Musculoskeletal Ultrasound imaging, synovial biopsy, biological samples collection, questionnaires.

Other: Musculoskeletal Ultrasound Imaging; Other: Synovial biopsy; Other: Biological samples collection; Other: Questionnaires

Interventions

Musculoskeletal Ultrasound Imaging OTHER

B-mode and PD musculoskeletal ultrasound examination of selected joints.

Conventional synthetic DMARD naïve; DMARD-IR: anti-CD20; DMARD-IR: anti-CTLA-4; DMARD-IR: anti-IL6; DMARD-IR: anti-TNF

Synovial biopsy OTHER

US guided synovial biopsy of an inflamed joint including wrists, MCP joints and knees.

Conventional synthetic DMARD naïve; DMARD-IR: anti-CD20; DMARD-IR: anti-CTLA-4; DMARD-IR: anti-IL6; DMARD-IR: anti-TNF

Biological samples collection OTHER

Draw of research blood samples.

Conventional synthetic DMARD naïve; DMARD-IR: anti-CD20; DMARD-IR: anti-CTLA-4; DMARD-IR: anti-IL6; DMARD-IR: anti-TNF

Questionnaires OTHER

Administration of validated patients' questionnaires.

Conventional synthetic DMARD naïve; DMARD-IR: anti-CD20; DMARD-IR: anti-CTLA-4; DMARD-IR: anti-IL6; DMARD-IR: anti-TNF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Rheumatoid Arthritis Patients

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Oxford: lead
• UCB Pharma: collaborator

Study Sites (1)

Nuffield Orthopaedic Centre

Oxford, OX3 7HE, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood and and Biologic samples collected will be processed in the CTU Translational Research Lab and stored within the Botnar Research Centre adhering to local guidelines on sample requirements, handling and storage. All biological samples will be available for future studies for biomarker profiling. The following blood samples will be drawn in order: 1. Two (10.0ml) K2EDTA tube 2. One (5.0ml) SST tube 3. One (3 ml) Tempus RNA tube 4. One (6 ml) DNA EDTA tube (only during Visit 1)

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Peter C Taylor, PhD, FRCP

  Kennedy Institute of Rheumatology, University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2015
• First Posted: June 19, 2015
• Study Start: October 13, 2014
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2021
• Last Updated: May 20, 2022

Record last verified: 2020-10

Locations

GB (1)