Rheumatoid ArthritisPRECISE-RANCT04482335
PRECISion medicinE Across the Disease Continuum to Prevent and Treat Rheumatoid Arthritis
An observational study of Rheumatoid Arthritis, run by University of Manchester at 1 site in United Kingdom.
Trial summary
The study will recruit patients referred to the Rheumatology Out-patient departments. Patients will be recruited to the study or control groups (healthy or disease controls who will be age and sex-matched) as needed. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis
- How many people
- 500 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 15 May 2021to 1 Oct 2025
- Phase
- Observational
- 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: People with early rheumatoid arthritis
Who may be able to join
- Subject ≥ 18 years of age
- Is capable of understanding and signing an informed consent form
- Falls into one of the following:
- Pre-RA - Any musculoskeletal symptom (inflammatory and/or non-inflammatory) AND either RF and/orACPA positive.
- UA - Inflammatory joint symptoms (including joint pain, significant early morning stiffness and joint swelling) not fulfilling any classification criteria
- ERA - recent clinical diagnosis of RA EstRA - known diagnosis of RA supported by evidence of established inflammatory arthritis including but not limited to synovitis, erosion, tenosynovitis.
Who cannot join
- Age less than 18 years
- Lack of capacity to give informed consent
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Manchester Royal Infirmary
Manchester, Greater Manchester, M13 9WL
Maya H Buch, MD PhD, +44 (0)161 306 0539, maya.buch@manchester.ac.uk
Rudresh Shukla, +44 (0)161 306 0539, rudresh.shukla@manchester.ac.uk
About this study
The study will recruit patients referred to the Rheumatology Out-patient departments. Patients will be recruited to the study or control groups (healthy or disease controls who will be age and sex-matched) as needed. The study will first open to recruitment at Manchester University Hospitals NHS Foundation Trust and then open at other NHS Trusts. Patients will be asked to participate in longitudinal (clinical/imaging/biosample) data and/or sample collection that will improve our understanding of underlying disease mechanisms and identify improved diagnostic, prognostic and predictive biomarkers to understand progression of disease and drug response or resistance.
Read the detailed description
Main Study
Consent to this ethics' main programme will permit collection of routinely collected data and use for research activities. Patients may be recruited at any point along their disease continuum (e.g. time of initial diagnosis, before/after a new treatment intervention, at time of disease flare or stable state).
Patients with established disease who are recruited to the study during their follow up appointments will have pre-existing results and clinical documentation. These retrospective data may also be collected where possible using information documented in case-notes and/or hospital information systems.
Some study-specific information will also be collected.
In addition to the main study, participants will be offered the opportunity to consent to participate in one or more sub-studies which include the additional research procedures (entitled 'basic biological' and 'synovial biopsy'). It will be possible for patients to participate in more than one sub-study.
The sub-studies aim to explore the mechanisms that may underlie change over the disease continuum, not just at disease initiation. In particular, the researchers would wish to obtain samples and imaging that coincide with a change in disease profile as well as with loss of disease control. Acquiring pre- and post-treatment blood/tissue samples and images would allow the investigation of changes in disease pathogenesis, the role of specific therapies, and identification of treatment response indicators. The researchers would therefore ask the permission of some individuals to obtain samples or images at additional time-points to coincide with events along their disease continuum.
Basic Biological sub-study
This sub-study will facilitate identification of prognostic markers of disease, mechanism and predictive markers of drug response. As part of an in-house investigation of biomarkers and mechanisms, DNA, serum, plasma, synovial joint fluid, and urine may be collected and stored. Patients will have the opportunity to consent separately to the genetic (DNA) component.
A maximum of 75mls of blood may be taken to enable the range of experimental studies. The samples will be taken at relevant clinical time points related to diagnosis, disease profile, disease activity state and/or treatment related time points; thus samples may be taken at one time point or repeated depending on the individual study objective and status of the patient.
Synovial biopsy sub-study
Patients will be asked to consent to a synovial biopsy of an affected joint to provide synovial tissue for research purposes. Synovial joint fluid may also be collected as part of the biopsy procedure. This will be performed by a trained clinician within our department by ultrasound-guidance. Depending on the research question being addressed, biopsy may be taken at time of diagnosis; or before and after starting a new drug treatment; or at time of a change in disease activity/flare (that may/may not lead to change in therapy). If repeat biopsy is taken, this is typically 3 or 6 months after starting a new therapy; or may be a later time point if evaluating for change in disease characteristics and tissue biology over time.
- Conditions
- Rheumatoid Arthritis
- Being tested
- No intervention
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
No intervention
| Study group | Role | What they receive |
|---|---|---|
| Main Study | Participants complete questionnaires and agree to have their retrospective and prospective medical data used as part f this research project. All participants will take part in this arm. Receives: Other: No intervention | |
| Biosample Sub-Study | A subset of the participants will take part of this. Participants will agree to have blood samples taken at regular intervals or at the point of a flare or when their treatment changes. They might also be asked to provide urine samples. Receives: Other: No intervention | |
| Synovial Biopsy and Synovial Fluid Sub-Study | A subset of the participants will take part of this. Participants will agree to synovial biopsies at regular intervals or at the point of a flare or when their treatment changes. They might also be asked to donate waste synovial fluid. Receives: Other: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
• Main study - Change in Disease Activity Score in 28 Joints (DAS28)
- The Disease Activity Score (DAS) assessment is a derived measurement with differential weight given to each component. The DAS28 is calculated at every visit. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment (0-100). The components of the DAS28 CRP score assessment are: Tender/Painful Joint Count (28); Swollen Joint Count (28), CRP, and the Subject General Health VAS assessment (0-100). The DAS score ranges from 0-10 and higher scores indicate high disease activity. A DAS28 value of >5.1 indicates high disease activity, 3.2 <DAS28 ≤5.1 and DAS28 ≤3.2 are defined as moderate and low disease activity. Patients may be considered to be in remission phase if DAS28 is <2.6
Measured: through to study completion, an average of 2 years
• Biosample substudy - Change in serum biomarkers, gene expression and the distribution of cell populations in biological samples (peripheral blood, synovial fluid, urine) using ELISA, sequencing, flow cytometry and CyTOF
- Biosample substudy - Change in serum biomarkers, gene expression and the distribution of cell populations in biological samples (peripheral blood, synovial fluid, urine) using ELISA, sequencing, flow cytometry and CyTOF
Measured: through to study completion, an average of 2 years
• Synovial biopsy substudy - Changes in immunological markers of inflammation in synovial tissue
- Synovial biopsy substudy - Changes in immunological markers of inflammation in synovial tissue
Measured: Baseline +/- week 12 or 24 after change in therapy
Secondary outcomes (12)
• Change in Patient reported outcome measure - Rheumatoid Arthritis Quality of Life (RAQoL)
- The RAQoL questionnaire consists of 30 items. The overall score is the sum of individual item scores, with a lower score indicating better QoL (range 0-30)
Measured: through to study completion, an average of 2 years
• Change in Patient reported outcome measure - Health Assessment Questionnaire (HAQ)
- The HAQ questions are assessed on a 4-point Likert scale (0 = without difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). Total HAQ score ranges from 0-3.0 in increments of 0.125. Higher scores indicate worse functioning.
Measured: through to study completion, an average of 2 years
• Change in Patient reported outcome measure - EuroQoL (EQ-5D)
- The EQ-5D consists of 5 domains (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) rated on a 3 level scale (no problems, some or moderate problems, extreme problems). Rated levels are coded as number 1, 2 or 3 and reported as a five-digit number ranging from 11111 (no problems in all domains) to 55555 (extreme problems in all domains)
Measured: through to study completion, an average of 2 years
• Change in Patient reported outcome measure - Functional Assessment of Chronic Illness Therapy - fatigue (FACIT-fatigue)
- FACIT-fatigue is a 13-item instrument measure of fatigue scored on a 0-4 response scale. All items are summed to create a final score (range 0-52). Higher scores indicate greater fatigue.
Measured: through to study completion, an average of 2 years
• Change in Patient reported outcome measure - Hospital Anxiety and Depression Scale (HADs)
- HADs consists of two subscales (anxiety and depression) with a total of 14 items - each scored on a scale from 0 to 3. Total scores range from 0-21 for each subscale (0-7 = normal, 9-10 = borderline abnormal, 11-21 = abnormal)
Measured: through to study completion, an average of 2 years
• Change in Patient-completed visual analogue scales - pain (VAS-pain)
- VAS-pain measures pain on the day on a visual analogue scale (range 0-100) with higher scores indicating worse pain
Measured: through to study completion, an average of 2 years
• Change in Patient-completed visual analogue scales - disease activity (VAS-DA)
- VAS-DA measures the state of arthritis (swelling and stiffness) on the day on a visual analogue scale (range 0-100) with higher scores indicating extremely active arthritis
Measured: through to study completion, an average of 2 years
• Change in Patient-completed visual analogue scales - fatigue (VAS-fatigue)
•VAS-fatigue measures overall fatigue on the day on a visual analogue scale (range 0-100) with higher scores indicating worse fatigue
Measured: through to study completion, an average of 2 years
• Change in Patient-completed visual analogue scales - general health (VAS-GH)
- VAS-GH measures general state of health on the day on a visual analogue scale (range 0-100) with higher scores indicating poor state of health
Measured: through to study completion, an average of 2 years
• Change in Physician-completed visual analogue scale of disease activity
- Physician-completed visual analogue scale of disease activity measures disease activity as rated by the physician on a visual analogue scale (range 0-100) with higher scores indicating extremely active disease
Measured: through to study completion, an average of 2 years
• Change in joint damage as measured by conventional radiography of hands and feet
- Change in joint damage as measured by conventional radiography of hands and feet
Measured: through to study completion, an average of 2 years
• Change from baseline in Ultrasound (US) synovitis as measured by Power Doppler Ultrasound (PDUS)
- Change from baseline in Ultrasound synovitis as measured by Power Doppler Ultrasound (PDUS)
Measured: through to study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2020
- Study start15 May 2021
- Primary completion1 Oct 2025 (estimated)
- Study completion1 Oct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by University of ManchesterThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Manchester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Maya H. Buch, University of Manchester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04482335
- Sponsor's protocol ID
- 281253
- Acronym
- PRECISE-RA
- Status last verified
- Sep 2021
- First submitted
- 8 Apr 2020
- Last updated
- 6 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PRECISion medicinE Across the Disease Continuum to Prevent and Treat Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT04482335
- Acronym / sponsor ID
- PRECISE-RA / 281253
- Conditions
- Rheumatoid Arthritis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- University of ManchesterUniversity, hospital or other
- Study start
- 15 May 2021 (actual)
- Primary completion
- 1 Oct 2025 (estimated)
- Study completion
- 1 Oct 2025 (estimated)
- First posted
- 22 Jul 2020 (actual)
- 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.
The study will recruit patients referred to the Rheumatology Out-patient departments. Patients will be recruited to the study or control groups (healthy or disease controls who will be age and sex-matched) as needed. The study will first open to recruitment at Manchester University Hospitals NHS Foundation Trust and then open at other NHS Trusts. Patients will be asked to participate in longitudinal (clinical/imaging/biosample) data and/or sample collection that will improve our understanding of underlying disease mechanisms and identify improved diagnostic, prognostic and predictive biomarkers to understand progression of disease and drug response or resistance.
Detailed description
Main Study
Consent to this ethics' main programme will permit collection of routinely collected data and use for research activities. Patients may be recruited at any point along their disease continuum (e.g. time of initial diagnosis, before/after a new treatment intervention, at time of disease flare or stable state).
Patients with established disease who are recruited to the study during their follow up appointments will have pre-existing results and clinical documentation. These retrospective data may also be collected where possible using information documented in case-notes and/or hospital information systems.
Some study-specific information will also be collected.
In addition to the main study, participants will be offered the opportunity to consent to participate in one or more sub-studies which include the additional research procedures (entitled 'basic biological' and 'synovial biopsy'). It will be possible for patients to participate in more than one sub-study.
The sub-studies aim to explore the mechanisms that may underlie change over the disease continuum, not just at disease initiation. In particular, the researchers would wish to obtain samples and imaging that coincide with a change in disease profile as well as with loss of disease control. Acquiring pre- and post-treatment blood/tissue samples and images would allow the investigation of changes in disease pathogenesis, the role of specific therapies, and identification of treatment response indicators. The researchers would therefore ask the permission of some individuals to obtain samples or images at additional time-points to coincide with events along their disease continuum.
Basic Biological sub-study
This sub-study will facilitate identification of prognostic markers of disease, mechanism and predictive markers of drug response. As part of an in-house investigation of biomarkers and mechanisms, DNA, serum, plasma, synovial joint fluid, and urine may be collected and stored. Patients will have the opportunity to consent separately to the genetic (DNA) component.
A maximum of 75mls of blood may be taken to enable the range of experimental studies. The samples will be taken at relevant clinical time points related to diagnosis, disease profile, disease activity state and/or treatment related time points; thus samples may be taken at one time point or repeated depending on the individual study objective and status of the patient.
Synovial biopsy sub-study
Patients will be asked to consent to a synovial biopsy of an affected joint to provide synovial tissue for research purposes. Synovial joint fluid may also be collected as part of the biopsy procedure. This will be performed by a trained clinician within our department by ultrasound-guidance. Depending on the research question being addressed, biopsy may be taken at time of diagnosis; or before and after starting a new drug treatment; or at time of a change in disease activity/flare (that may/may not lead to change in therapy). If repeat biopsy is taken, this is typically 3 or 6 months after starting a new therapy; or may be a later time point if evaluating for change in disease characteristics and tissue biology over time.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Main Study | – | Other: No interventionParticipants complete questionnaires and agree to have their retrospective and prospective medical data used as part f this research project. All participants will take part in this arm. |
| Biosample Sub-Study | – | Other: No interventionA subset of the participants will take part of this. Participants will agree to have blood samples taken at regular intervals or at the point of a flare or when their treatment changes. They might also be asked to provide urine samples. |
| Synovial Biopsy and Synovial Fluid Sub-Study | – | Other: No interventionA subset of the participants will take part of this. Participants will agree to synovial biopsies at regular intervals or at the point of a flare or when their treatment changes. They might also be asked to donate waste synovial fluid. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- People with early rheumatoid arthritis
Key inclusion criteria (6 listed)
- Subject ≥ 18 years of age
- Is capable of understanding and signing an informed consent form
- Falls into one of the following:
Key exclusion criteria (2 listed)
- Age less than 18 years
- Lack of capacity to give informed consent
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 |
|---|---|---|
| No interventionNo intervention | Other | Biosample Sub-Study, Main Study, Synovial Biopsy and Synovial Fluid Sub-Study |
Primary outcome
• Main study - Change in Disease Activity Score in 28 Joints (DAS28)
Time frame: through to study completion, an average of 2 years
• The Disease Activity Score (DAS) assessment is a derived measurement with differential weight given to each component. The DAS28 is calculated at every visit. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment (0-100). The components of the DAS28 CRP score assessment are: Tender/Painful Joint Count (28); Swollen Joint Count (28), CRP, and the Subject General Health VAS assessment (0-100). The DAS score ranges from 0-10 and higher scores indicate high disease activity. A DAS28 value of >5.1 indicates high disease activity, 3.2 <DAS28 ≤5.1 and DAS28 ≤3.2 are defined as moderate and low disease activity. Patients may be considered to be in remission phase if DAS28 is <2.6
• Biosample substudy - Change in serum biomarkers, gene expression and the distribution of cell populations in biological samples (peripheral blood, synovial fluid, urine) using ELISA, sequencing, flow cytometry and CyTOF
Time frame: through to study completion, an average of 2 years
• Biosample substudy - Change in serum biomarkers, gene expression and the distribution of cell populations in biological samples (peripheral blood, synovial fluid, urine) using ELISA, sequencing, flow cytometry and CyTOF
• Synovial biopsy substudy - Changes in immunological markers of inflammation in synovial tissue
Time frame: Baseline +/- week 12 or 24 after change in therapy
• Synovial biopsy substudy - Changes in immunological markers of inflammation in synovial tissue
12 secondary outcomes
• Change in Patient reported outcome measure - Rheumatoid Arthritis Quality of Life (RAQoL)
Time frame: through to study completion, an average of 2 years
• Change in Patient reported outcome measure - Health Assessment Questionnaire (HAQ)
Time frame: through to study completion, an average of 2 years
• Change in Patient reported outcome measure - EuroQoL (EQ-5D)
Time frame: through to study completion, an average of 2 years
• Change in Patient reported outcome measure - Functional Assessment of Chronic Illness Therapy - fatigue (FACIT-fatigue)
Time frame: through to study completion, an average of 2 years
• Change in Patient reported outcome measure - Hospital Anxiety and Depression Scale (HADs)
Time frame: through to study completion, an average of 2 years
• Change in Patient-completed visual analogue scales - pain (VAS-pain)
Time frame: through to study completion, an average of 2 years
• Change in Patient-completed visual analogue scales - disease activity (VAS-DA)
Time frame: through to study completion, an average of 2 years
• Change in Patient-completed visual analogue scales - fatigue (VAS-fatigue)
Time frame: through to study completion, an average of 2 years
• Change in Patient-completed visual analogue scales - general health (VAS-GH)
Time frame: through to study completion, an average of 2 years
• Change in Physician-completed visual analogue scale of disease activity
Time frame: through to study completion, an average of 2 years
• Change in joint damage as measured by conventional radiography of hands and feet
Time frame: through to study completion, an average of 2 years
• Change from baseline in Ultrasound (US) synovitis as measured by Power Doppler Ultrasound (PDUS)
Time frame: through to study completion, an average of 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2021.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rheumatoid Arthritis, run by University of Manchester 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 6 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 6 Oct 2021. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
• Main study - Change in Disease Activity Score in 28 Joints (DAS28) (time frame: through to study completion, an average of 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Oct 2021.