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Targeting Synovitis in Early Rheumatoid Arthritis (TaSER)

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ClinicalTrials.gov Identifier: NCT00920478
Recruitment Status : Unknown
Verified September 2009 by NHS Greater Glasgow and Clyde.
Recruitment status was:  Recruiting
First Posted : June 15, 2009
Last Update Posted : September 10, 2009
Sponsor:
Collaborators:
University of Glasgow
Chief Scientist Office of the Scottish Government
Wyeth is now a wholly owned subsidiary of Pfizer
Translational Medicine Research Collaboration
Information provided by:
NHS Greater Glasgow and Clyde

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Polyarthritis Other: Musculoskeletal Ultrasound Other: 28 Joint Disease Activity Score Phase 4

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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  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : September 2009
Estimated Primary Completion Date : September 2012
Estimated Study Completion Date : September 2012


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



Primary Outcome Measures :
  1. MRI RAMRIS Erosion Score [ Time Frame: Baseline and 18 months ]
  2. 44 Joint Disease Activity Score [ Time Frame: Baseline, 3, 6, 9, 12, 15 and 18 months ]

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


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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00920478


Contacts
Contact: James Dale, MBChB, MRCP +44 141 211 3000 ext 3008 james.dale@ggc.scot.nhs.uk

Locations
United Kingdom
Department of Rheumatology, Gartnavel General Hospital Recruiting
Glasgow, United Kingdom, G12 0YN
Contact: Duncan Porter, MBChB    +44 141 211 3000    duncan.porter@ggc.scot.nhs.uk   
Principal Investigator: Duncan Porter, MBChB, MRCP         
Department of Rheumatology, Stobhill Hospital Recruiting
Glasgow, United Kingdom, G21 3UW
Contact: Hilary Wilson, MD, MRCP    +44 141 211 3307    hilary.wilson@ggc.scot.nhs.uk   
Principal Investigator: Hilary Wilson, MD, MRCP         
Centre for Rheumatic Diseases, Glasgow Royal Infirmary Recruiting
Glasgow, United Kingdom, G4 0SF
Contact: David McCarey, MBChB, FRCP    +44 141 2114965    david.mccarey@ggc.scot.nhs.uk   
Principal Investigator: David McCarey, MD, FRCP         
Sponsors and Collaborators
NHS Greater Glasgow and Clyde
University of Glasgow
Chief Scientist Office of the Scottish Government
Wyeth is now a wholly owned subsidiary of Pfizer
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 automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr James Dale, University of Glasgow and National Health Service
ClinicalTrials.gov Identifier: NCT00920478     History of Changes
Other Study ID Numbers: GN09RH196
CSO - CAF / 08 / 03
First Posted: June 15, 2009    Key Record Dates
Last Update Posted: September 10, 2009
Last Verified: September 2009

Keywords provided by NHS Greater Glasgow and Clyde:
Rheumatoid arthritis
Musculoskeletal Ultrasound
Synovitis
DMARD
Etanercept
Biomarkers
Undifferentiated Inflammatory Polyarthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Synovitis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases