Rheumatoid ArthritisBioRRANCT02219347
Biomarkers of Remission in Rheumatoid Arthritis (BioRRA)
A study testing DMARD cessation in people with Rheumatoid Arthritis, run by Newcastle-upon-Tyne Hospitals NHS Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- DMARD cessation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2014to Aug 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Newcastle NIHR Clinical Research Facility, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust
Newcastle upon Tyne, Tyne & Wear, NE1 4LP
About this study
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.
Read more
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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- DMARD cessation
- Keywords
- rheumatoid arthritis, biological markers, remission, ultrasonography, microarray, survival analysis, T cell
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DMARD cessationDrug
Complete cessation of non-biologic DMARD therapy (single or combination of methotrexate, sulphasalazine and/or hydroxychloroquine)
| Study group | Role | What they receive |
|---|---|---|
| DMARD cessation | Other | 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. Receives: Drug: DMARD cessation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: From recruitment, assessed up to 6 months
Secondary outcomes (6)
Clinical biomarkers predictive of DMARD-free remission
Baseline clinical factors predictive of time-to-flare of arthritis activity following DMARD cessation.
Measured: At recruitment
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.
Measured: At recruitment
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.
Measured: At recruitment
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.
Measured: At recruitment
Rheumatoid arthritis disease activity
Measured by Disease Activity Score in 28 joints (DAS28-CRP) score.
Measured: At recruitment and at 1 month, 3 months and 6 months following DMARD cessation
Physical disability
Measured by Health Assessment Questionnaire Disability Index (HAQ-DI) questionnaire
Measured: At baseline and at 6 months following DMARD cessation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2014 (estimated)
- Study startAug 2014
- Primary completionAug 2017
- Study completionAug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Newcastle-upon-Tyne Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Newcastle University, Wellcome Trust
- Responsible party
- Sponsor
- Investigators
- John D Isaacs, PhD MBBS, Principal investigator, Newcastle University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02219347
- Sponsor's protocol ID
- NUTH7100
- Acronym
- BioRRA
- Status last verified
- Nov 2017
- First submitted
- 15 Aug 2014
- Last updated
- 6 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Baker KF, McDonald D, Hulme G, Hussain R, Coxhead J, Swan D, Schulz AR, Mei HE, MacDonald L, Pratt AG, Filby A, Anderson AE, Isaacs JD. Single-cell insights into immune dysregulation in rheumatoid arthritis flare versus drug-free remission. Nat Commun. 2024 Feb 5;15(1):1063. doi: 10.1038/s41467-024-45213-2.
PubMed 38316770
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarkers of Remission in Rheumatoid Arthritis (BioRRA)
- ClinicalTrials.gov ID
- NCT02219347
- Acronym / sponsor ID
- BioRRA / NUTH7100
- Conditions
- Rheumatoid Arthritis
- Keywords
- rheumatoid arthritis, biological markers, remission, ultrasonography, microarray, survival analysis, T cell
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Newcastle-upon-Tyne Hospitals NHS TrustUniversity, hospital or other
- Collaborators
- Newcastle University, Wellcome Trust
- Study start
- Aug 2014 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 18 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DMARD cessation | Other | Drug: DMARD cessationAll 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DMARD cessationComplete cessation of non-biologic DMARD therapy (single or combination of methotrexate, sulphasalazine and/or hydroxychloroquine) | Drug | DMARD cessation |
Primary outcome
Time-to-flare of arthritis activity following DMARD cessation
Time frame: From recruitment, assessed up to 6 months
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
6 secondary outcomes
Clinical biomarkers predictive of DMARD-free remission
Time frame: At recruitment
Ultrasound biomarkers of DMARD-free remission
Time frame: At recruitment
Genetic biomarkers of DMARD-free remission
Time frame: At recruitment
Cytokine biomarkers of DMARD-free remission
Time frame: At recruitment
Rheumatoid arthritis disease activity
Time frame: At recruitment and at 1 month, 3 months and 6 months following DMARD cessation
Physical disability
Time frame: At baseline and at 6 months following DMARD cessation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2017.
- Derived from this study: PubMed 38316770Baker KF, McDonald D, Hulme G, Hussain R, Coxhead J, Swan D, Schulz AR, Mei HE, MacDonald L, Pratt AG, Filby A, Anderson AE, Isaacs JD. Single-cell insights into immune dysregulation in rheumatoid arthritis flare versus drug-free remission. Nat Commun. 2024 Feb 5;15(1):1063. doi: 10.1038/s41467-024-45213-2.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John D Isaacs, PhD MBBS principal investigator
Newcastle University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing DMARD cessation in people with Rheumatoid Arthritis, run by Newcastle-upon-Tyne Hospitals NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time-to-flare of arthritis activity following DMARD cessation (time frame: From recruitment, assessed up to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02219347, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2017.