Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) (BioRRA)
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
DMARD cessation
Sponsored by
About this trial
This is an interventional basic science trial for Rheumatoid Arthritis focused on measuring rheumatoid arthritis, biological markers, remission, ultrasonography, microarray, survival analysis, T cell
Eligibility Criteria
Inclusion Criteria:
- Clinical diagnosis of rheumatoid arthritis made by consultant rheumatologist at least 12 months previously
- Current single or combination use of methotrexate, sulphasalazine and/or hydroxychloroquine
- Arthritis currently in remission, as judged clinically by referring healthcare professional
- Willing to consider DMARD withdrawal
Exclusion Criteria:
- Use of biologic therapy within the past 6 months
- Received steroids within past 3 months (enteral, parenteral or intra-articular)
- Use of any DMARD other than methotrexate, sulphasalazine or hydroxychloroquine within the past 6 months (or past 12 months for leflunomide)
- Current pregnancy, or pregnancy planned within next 6 months
- Current participation within another clinical trial
- Inability to provide informed consent
Sites / Locations
- Newcastle NIHR Clinical Research Facility, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
DMARD cessation
Arm Description
All patients recruited to the study who have a Disease Activity in 28 Joints C-Reactive Protein (DAS28-CRP) score of < 2.4 and who do not have power Doppler synovitis on a 7-joint musculoskeletal ultrasound scan will stop their DMARD therapy. These patients will then be followed-up for a period of 6 months or until flare of their arthritis activity, whichever is sooner.
Outcomes
Primary Outcome Measures
Time-to-flare of arthritis activity following DMARD cessation
Flare of arthritis activity defined as Disease Activity Score in 28 Joints C-Reactive Protein (DAS28-CRP) score greater than or equal to 2.4
Secondary Outcome Measures
Clinical biomarkers predictive of DMARD-free remission
Baseline clinical factors predictive of time-to-flare of arthritis activity following DMARD cessation.
Ultrasound biomarkers of DMARD-free remission
Baseline musculoskeletal ultrasound biomarkers predictive of time-to-flare of arthritis activity following DMARD cessation, including presence or absence of greyscale synovitis/tenosynovitis and erosions.
Genetic biomarkers of DMARD-free remission
Baseline signature of differential gene expression in peripheral CD4+ T cells predictive of DMARD-free remission at 6 months following DMARD cessation, as measured using RNA sequencing.
Cytokine biomarkers of DMARD-free remission
Baseline signature of differential cytokine levels in peripheral blood predictive of time-to-flare of arthritis activity, as measured using a multiplex cytokine assay.
Rheumatoid arthritis disease activity
Measured by Disease Activity Score in 28 joints (DAS28-CRP) score.
Physical disability
Measured by Health Assessment Questionnaire Disability Index (HAQ-DI) questionnaire
Full Information
NCT ID
NCT02219347
First Posted
August 15, 2014
Last Updated
November 1, 2017
Sponsor
Newcastle-upon-Tyne Hospitals NHS Trust
Collaborators
Newcastle University, Wellcome Trust
1. Study Identification
Unique Protocol Identification Number
NCT02219347
Brief Title
Biomarkers of Remission in Rheumatoid Arthritis (BioRRA)
Acronym
BioRRA
Official Title
Biomarkers of Remission in Rheumatoid Arthritis (BioRRA)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
August 2014 (Actual)
Primary Completion Date
August 2017 (Actual)
Study Completion Date
August 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Newcastle-upon-Tyne Hospitals NHS Trust
Collaborators
Newcastle University, Wellcome Trust
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Rheumatoid arthritis is a common condition affecting approximately 1% of the United Kingdom population; it is an autoimmune disease where the body's natural defences (the immune system) attack the body itself resulting, most notably, in joint damage and arthritis. To help prevent this, patients with rheumatoid arthritis need to take disease-modifying anti-rheumatic drugs (DMARDs). As rheumatoid arthritis is a life-long condition, these drug treatments are prescribed as long-term medications taken for many years.
With successful drug treatment, many patients are able to achieve an excellent control of their disease and their arthritis can go in to remission. At present, there are no markers which can reliably predict which of these patients can reduce their drug treatment, and hence benefit from a lower risk of side effects and inconvenience, without an increase in their arthritis activity.
We invite patients with stable rheumatoid arthritis to participate in this study conducted by Newcastle upon Tyne Hospitals NHS Foundation Trust in collaboration with Newcastle University and funded by the Wellcome Trust. Patients whose arthritis is confirmed as being in remission will be able to stop their DMARD medication and be monitored for a period of 6 months. Patients whose arthritis activity increases during this time will be able to restart their DMARD medication, whereas those patients whose arthritis remains in remission will be able to stay off DMARD medication.
The main aim of this study is to identify clinical, ultrasound and blood markers that can predict which patients will remain in remission after stopping DMARD medication. If identified, these markers could be a useful guide to doctors and patients in the future when deciding whether to stop DMARD therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
rheumatoid arthritis, biological markers, remission, ultrasonography, microarray, survival analysis, T cell
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
74 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DMARD cessation
Arm Type
Other
Arm Description
All patients recruited to the study who have a Disease Activity in 28 Joints C-Reactive Protein (DAS28-CRP) score of < 2.4 and who do not have power Doppler synovitis on a 7-joint musculoskeletal ultrasound scan will stop their DMARD therapy. These patients will then be followed-up for a period of 6 months or until flare of their arthritis activity, whichever is sooner.
Intervention Type
Drug
Intervention Name(s)
DMARD cessation
Intervention Description
Complete cessation of non-biologic DMARD therapy (single or combination of methotrexate, sulphasalazine and/or hydroxychloroquine)
Primary Outcome Measure Information:
Title
Time-to-flare of arthritis activity following DMARD cessation
Description
Flare of arthritis activity defined as Disease Activity Score in 28 Joints C-Reactive Protein (DAS28-CRP) score greater than or equal to 2.4
Time Frame
From recruitment, assessed up to 6 months
Secondary Outcome Measure Information:
Title
Clinical biomarkers predictive of DMARD-free remission
Description
Baseline clinical factors predictive of time-to-flare of arthritis activity following DMARD cessation.
Time Frame
At recruitment
Title
Ultrasound biomarkers of DMARD-free remission
Description
Baseline musculoskeletal ultrasound biomarkers predictive of time-to-flare of arthritis activity following DMARD cessation, including presence or absence of greyscale synovitis/tenosynovitis and erosions.
Time Frame
At recruitment
Title
Genetic biomarkers of DMARD-free remission
Description
Baseline signature of differential gene expression in peripheral CD4+ T cells predictive of DMARD-free remission at 6 months following DMARD cessation, as measured using RNA sequencing.
Time Frame
At recruitment
Title
Cytokine biomarkers of DMARD-free remission
Description
Baseline signature of differential cytokine levels in peripheral blood predictive of time-to-flare of arthritis activity, as measured using a multiplex cytokine assay.
Time Frame
At recruitment
Title
Rheumatoid arthritis disease activity
Description
Measured by Disease Activity Score in 28 joints (DAS28-CRP) score.
Time Frame
At recruitment and at 1 month, 3 months and 6 months following DMARD cessation
Title
Physical disability
Description
Measured by Health Assessment Questionnaire Disability Index (HAQ-DI) questionnaire
Time Frame
At baseline and at 6 months following DMARD cessation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Clinical diagnosis of rheumatoid arthritis made by consultant rheumatologist at least 12 months previously
Current single or combination use of methotrexate, sulphasalazine and/or hydroxychloroquine
Arthritis currently in remission, as judged clinically by referring healthcare professional
Willing to consider DMARD withdrawal
Exclusion Criteria:
Use of biologic therapy within the past 6 months
Received steroids within past 3 months (enteral, parenteral or intra-articular)
Use of any DMARD other than methotrexate, sulphasalazine or hydroxychloroquine within the past 6 months (or past 12 months for leflunomide)
Current pregnancy, or pregnancy planned within next 6 months
Current participation within another clinical trial
Inability to provide informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John D Isaacs, PhD MBBS
Organizational Affiliation
Newcastle University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Newcastle NIHR Clinical Research Facility, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust
City
Newcastle upon Tyne
State/Province
Tyne & Wear
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
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Biomarkers of Remission in Rheumatoid Arthritis (BioRRA)
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