Targeting Synovitis in Early Rheumatoid Arthritis (TaSER)

September 9, 2009 updated by: NHS Greater Glasgow and Clyde

Targeting Synovitis in Early Rheumatoid Arthritis (TaSER). Intensive Management of Early Rheumatoid Arthritis Using Either Clinical or Musculoskeletal Ultrasound Assessment of Synovitis - a Randomised Study With Blinded Outcome Assessments

Patients with rheumatoid arthritis are at risk of developing permanent joint damage and disability. This study hopes to identify the most effective way of using existing arthritis medication to minimise the chances of developing permanent disability. Patients will have their arthritis activity assessed using an ultrasound machine. If there is still evidence of active arthritis the participant's arthritis medication will be increased until the arthritis is in remission. The effectiveness of this approach will be compared to the traditional method of assessing arthritis using clinical examination.

Furthermore, it is extremely important to identify those patients most at risk of aggressive disease. The investigators hope to produce a more accurate measurement of disease prognosis by examining the relationship between a series of blood tests and how well controlled rheumatoid arthritis appears after 18 months of therapy. Some patients will also be asked to donate samples of joint fluid and joint lining for additional analysis.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

PURPOSE 1 - to determine whether it is possible to achieve better control of inflammatory joint disease activity in early rheumatoid arthritis by using musculoskeletal ultrasound, instead of clinical examination, to identify the presence, or absence, of synovitis

NULL HYPOTHESIS 1 - using musculoskeletal ultrasound to confirm / refute the presence of ongoing synovitis will NOT allow better control of early rheumatoid arthritis nor prevent progression of destructive joint disease despite patients receiving more intensive disease modifying therapy regimens

PURPOSE 2 - to determine whether baseline measures of certain biochemical and pathological factors, associated with the development of inflammatory synovitis, are predictive of response to therapy in early rheumatoid arthritis and short term outcome measures of inflammatory joint disease activity, functional ability and quality of life

NULL HYPOTHESIS 2 - serial measures of biochemical and pathological factors, associated with the development of inflammatory synovitis, will NOT correlate with short term outcome measures of disease activity and therefore cannot be used to predict a patient's prognosis nor identify those at risk of progressive, destructive joint disease

TRIAL DESIGN - randomised, prospective single blinded trial of treatment strategy with a nested study correlating baseline measures and 18 month outcomes

Investigators will not be blinded to treatment group. Treatment decisions and escalation of therapy will be dictated by a standardised protocol. The sequence of therapy escalation will be identical for both groups. The groups will differ on the threshold needed to progress to the next treatment step

Assessors of disease activity, radiological and pathological outcomes will be blinded to treatment group and their findings will form the basis of each groups final outcome measures

TREATMENT PROTOCOL - the sequence of therapy escalation will be the same for each group. The groups differ by the 'trigger' required to progress to the next treatment step. Therapy will escalated in each group if the measured disease activity exceeds that groups threshold trigger. Changes in DMARD therapy doses and/or combinations take three months to reach maximum effect; therefore, at least a three month gap will be left between each treatment escalation

PRIMARY OUTCOME MEASURE

  1. Magnetic Resonance Imaging of Dominant Wrist - baseline and 18 months. Images will be scored using the OMERACT RAMRIS(Rheumatoid Arthritis Magnetic Resonance Imaging Score) atlas. The change in each patient's synovitis and erosion scores will be pooled and compared for each intervention group
  2. 44 joint Disease Activity Score - Mean change of DAS44 with time will represent the rate of response to treatment. Mean area under curve DAS44 will represent overall level of disease activity throughout the study period

SECONDARY OUTCOME MEASURES

  1. European League Against Rheumatism Response Rates - A EULAR Good response is defined as a greater than 1.2 change in DAS44 and a final DAS44 less than 2.4. Disease remission is defined as DAS44 less than 1.6
  2. Functional Measures - Health Assessment Questionnaire and EuroQoL-5D questionnaires at enrollment and then every 3 months.
  3. Plain Xrays - plain xrays of hands, wrists and feet at baseline and 18 months. Change in Sharp score between baseline and 18 month films will be reported
  4. Biomarker analysis - analyses will include specific genetic factors(genomic DNA), gene expression (RNA analysis), novel autoantibody assays, cytokine / emerging inflammatory protein profiling, lipid / lipoprotein based markers, metabolic assays and assessment of bone and cartilage turnover markers.

Samples will be collected at baseline, 3 months and 12 months (if not commenced on etanercept), immediately before commencing etanercept, 3 months and 6 months after commencing etanercept and 3 months after cessation. Final disease outcome measures for each patient will be correlated with baseline biomarker values to determine if any predictive relationships exist.

All values will be entered into a logistical regression analysis to try and create a statistical predictive model. Serial biomarker analyses will demonstrate how the different components of the pathogenetic process respond to the different stages of DMARD therapy.

Study Type

Interventional

Enrollment (Anticipated)

110

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United Kingdom
      • Glasgow, United Kingdom, G12 0YN
        • Recruiting
        • Department of Rheumatology, Gartnavel General Hospital
        • Contact:
        • Principal Investigator:
          • Duncan Porter, MBChB, MRCP
      • Glasgow, United Kingdom, G21 3UW
        • Recruiting
        • Department of Rheumatology, Stobhill Hospital
        • Contact:
        • Principal Investigator:
          • Hilary Wilson, MD, MRCP
      • Glasgow, United Kingdom, G4 0SF
        • Recruiting
        • Centre for Rheumatic Diseases, Glasgow Royal Infirmary
        • Contact:
        • Principal Investigator:
          • David McCarey, MD, FRCP

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients attending Early RA clinics with newly diagnosed RA or anti-CCP +ve Undifferentiated Arthritis (UA)
  2. Active disease (DAS28 > 3.2)
  3. DMARD naïve or DMARD monotherapy for less than 6 weeks
  4. Aged 18 or more

Exclusion Criteria:

  1. Significant liver disease and/or abnormality of liver function tests
  2. AST / ALT > x2 normal, Alkaline Phosphatase > x2.5 normal
  3. Renal impairment - serum creatinine > 200 μmol/l, eGFR < 30
  4. Cytopenias - white cell count < 4.0, haemoglobin < 10, platelet < 150
  5. Pregnancy or planned pregnancy
  6. Contraindication to MRI
  7. Other co-morbid condition that in the opinion of the investigator would preclude the use of sequential or combination DMARD therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Control Group
Inflammatory disease activity assessed using DAS28
Other: 28 Joint Disease Activity Score
Clinical assessment of synovitis - composite score incorporating 28 tender joint count, 28 swollen joint count, erythrocyte sedimentation rate and patient global VAS
Experimental: Ultrasound Group
Inflammatory disease activity assessed using musculoskeletal ultrasound (gray scale and power doppler)
Other: Musculoskeletal Ultrasound
Gray scale and power doppler - to identify the presence of synovitis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
MRI RAMRIS Erosion Score
Time Frame: Baseline and 18 months
Baseline and 18 months
44 Joint Disease Activity Score
Time Frame: Baseline, 3, 6, 9, 12, 15 and 18 months
Baseline, 3, 6, 9, 12, 15 and 18 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Plain Xray - Hands and Feet - modified Sharp score
Time Frame: Baseline and 18 months
Baseline and 18 months
Health Assessment Questionnaire
Time Frame: Baseline, 3, 6, 9, 12, 15 and 18 months
Baseline, 3, 6, 9, 12, 15 and 18 months
Euro-Qol 5D
Time Frame: Baseline, 3, 6, 9, 12, 15 and 18 months
Baseline, 3, 6, 9, 12, 15 and 18 months
EULAR response and remission rates
Time Frame: Baseline and 18 months
Baseline and 18 months
Biomarker analysis - correlation between baseline values and 18 month radiological outcomes
Time Frame: Baseline
Baseline
Adverse event rates
Time Frame: Throughout period of study
Throughout period of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NHS Greater Glasgow and Clyde

Collaborators

Wyeth is now a wholly owned subsidiary of Pfizer
University of Glasgow
Chief Scientist Office of the Scottish Government
Translational Medicine Research Collaboration

Investigators

  • Study Chair: Duncan R Porter, MBChB, MRCP, Gartnavel General Hospital, Glasgow
  • Principal Investigator: James E Dale, MBChB, MRCP, University of Glasgow
  • Study Chair: Iain B McInnes, PhD, FRCP, University of Glasgow

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (Anticipated)

September 1, 2012

Study Completion (Anticipated)

September 1, 2012

Study Registration Dates

First Submitted

June 11, 2009

First Submitted That Met QC Criteria

June 11, 2009

First Posted (Estimate)

June 15, 2009

Study Record Updates

Last Update Posted (Estimate)

September 10, 2009

Last Update Submitted That Met QC Criteria

September 9, 2009

Last Verified

September 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GN09RH196
  • CSO - CAF / 08 / 03

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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