Targeting Synovitis in Early Rheumatoid Arthritis

NCT00920478

Last updated date
Study Location
Department of Rheumatology, Gartnavel General Hospital
Glasgow, , G12 0YN, United Kingdom
Contact
+44 141 211 3000

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Rheumatoid Arthritis, Polyarthritis
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


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

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Rheumatoid Arthritis, PolyarthritisTargeting Synovitis in Early Rheumatoid Arthritis
NCT00920478
  1. Glasgow,
  2. Glasgow,
  3. Glasgow,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Targeting Synovitis in Early Rheumatoid Arthritis
Official Title  ICMJE 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
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Rheumatoid Arthritis
  • Polyarthritis
Intervention  ICMJE
  • Other: Musculoskeletal Ultrasound
    Gray scale and power doppler - to identify the presence of synovitis
  • 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
Study Arms  ICMJE
  • Active Comparator: Control Group
    Inflammatory disease activity assessed using DAS28
    Intervention: Other: 28 Joint Disease Activity Score
  • Experimental: Ultrasound Group
    Inflammatory disease activity assessed using musculoskeletal ultrasound (gray scale and power doppler)
    Intervention: Other: Musculoskeletal Ultrasound
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 11, 2009)
110
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2012
Estimated Primary Completion Date September 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 ?mol/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
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00920478
Other Study ID Numbers  ICMJE GN09RH196
CSO - CAF / 08 / 03
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr James Dale, University of Glasgow and National Health Service
Study Sponsor  ICMJE NHS Greater Glasgow and Clyde
Collaborators  ICMJE
  • University of Glasgow
  • Chief Scientist Office of the Scottish Government
  • Wyeth is now a wholly owned subsidiary of Pfizer
  • Translational Medicine Research Collaboration
Investigators  ICMJE
Study Chair:Duncan R Porter, MBChB, MRCPGartnavel General Hospital, Glasgow
Principal Investigator:James E Dale, MBChB, MRCPUniversity of Glasgow
Study Chair:Iain B McInnes, PhD, FRCPUniversity of Glasgow
PRS Account NHS Greater Glasgow and Clyde
Verification Date September 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP