An MRI-guided Treatment Strategy to Prevent Disease Progression in Patients With Rheumatoid Arthritis (IMAGINE-RA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by King Christian X´Hospital for Rheumatic Diseases
Sponsor:
Collaborators:
King Christian X´Hospital for Rheumatic Diseases
Slagelse Hospital
Glostrup University Hospital, Copenhagen
Abbott
Information provided by (Responsible Party):
Professor of Rheumatology, MD, DMSci, Kim Horslev-Petersen, King Christian X´Hospital for Rheumatic Diseases
ClinicalTrials.gov Identifier:
NCT01656278
First received: July 5, 2012
Last updated: March 11, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to examine whether an magnetic resonance imaging (MRI) -guided treatment strategy based on a predefined treatment algorithm can prevent progression of erosive joint damage, increase remission rate and improve functional level in the short and long term in patients with rheumatoid arthritis (RA).


Condition Intervention
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Procedure: Magnetic resonance imaging (MRI)
Other: Conventional biochemical and clinical examinations

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Does an MRI-guided Treatment Strategy Reduce Disease Activity and Progression in Patients With Rheumatoid Arthritis (RA): a Randomised Controlled Trial

Resource links provided by NLM:


Further study details as provided by King Christian X´Hospital for Rheumatic Diseases:

Primary Outcome Measures:
  • DAS28 remission (<2.6) [ Time Frame: 24 month ] [ Designated as safety issue: No ]
  • No radiographic progression (assessed by the Sharp/vdHeijde method). [ Time Frame: 24 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • No radiographic progression (Sharp/vdHeijde score). [ Time Frame: 24 month ] [ Designated as safety issue: No ]
    No radiographic progression (Sharp/vdHeijde score) from 0-12 and 12-24 months and change in Sharp/vdHeijde score from 0-12, 0-24 and 12-24 months.

  • No MRI erosion (RAMRIS) score [ Time Frame: 24 month ] [ Designated as safety issue: No ]
    No progression in MRI erosion (RAMRIS) score from 0-12 and 12-24 months and change in MRI erosion (RAMRIS) score from 0-12, 0-24 and 12-24 months.

  • MRI synovitis (RAMRIS) score [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    MRI synovitis (RAMRIS) score at 12 and 24 months

  • MRI bone marrow oedema (RAMRIS) score [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    MRI bone marrow oedema (RAMRIS) score at 12 and 24 months

  • HAQ score [ Time Frame: 24 month ] [ Designated as safety issue: No ]
    Changes in HAQ score from 0-12 and 0-24 months

  • SF-36 score [ Time Frame: 24 month ] [ Designated as safety issue: No ]
    Changes in SF-36 score from 0-12 and 0-24 months

  • EQ-5D score [ Time Frame: 24 month ] [ Designated as safety issue: No ]
    Changes in EQ-5D score from 0-12 and 0-24 months

  • ACR/EULAR 2011 remission [ Time Frame: 24 month ] [ Designated as safety issue: No ]
    ACR/EULAR 2011 remission at 12 and 24 months

  • DAS28 [ Time Frame: 24 month ] [ Designated as safety issue: No ]
    DAS28 at 12 and 24 month

  • DAS28 remission (<2.6) at 12 months [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • biomarker analyses [ Time Frame: 24 month ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Dynamic MRI [ Time Frame: 24 month ] [ Designated as safety issue: No ]
    Dynamic MRI variable (including initial rate of enhancement (IRE) and maximum enhancement (ME)).


Estimated Enrollment: 200
Study Start Date: March 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Conventional biochemical and clinical examinations
Treatment algorithm based on conventional biochemical and clinical examinations
Other: Conventional biochemical and clinical examinations
Treatment algorithm based on conventional biochemical and clinical examinations. Assessed month 0, 4, 8, 12, 16, 20, 24 with treatment intensification after predefined treatment algorithm in the case of "unsatisfactory inflammatory activity", which is defined as the presence of at least one clinically swollen joint and DAS28>3.2
Experimental: Conventional biochemical and clinical examinations and MRI.
Treatment algorithm based on conventional biochemical and clinical examinations and MRI.
Procedure: Magnetic resonance imaging (MRI)
Treatment algorithm based on conventional biochemical/clinical examinations AND MRI of unilateral 2nd to 5th MCP joints and wrist on dominant side. Assessed month 0, 4, 8, 12, 16, 20, 24 with treatment intensification after predefined treatment algorithm in the case of "unsatisfactory inflammatory activity", which is defined as the presence of at least one physically swollen joint and DAS28>3.2 AND/OR MRI-detected bone marrow oedema score > 0 (RAMRIS-score)

Detailed Description:

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease. Patients typically experience pain, functional impairment and reduced quality of life, and are at risk of developing progressive joint damage. The disease primarily affects the small joints of the hands and feet. The current treatment strategy involves early and intensive treatment with close clinical follow up, which attempts to control the disease and avoid inflammation and thereby prevent pain, improve functional level and avoid joint damage. It is therefore important for optimal treatment of RA patients that methods used for diagnosis, disease monitoring and prognostication are highly sensitive. Erosive joint damage occurs early in the disease. Joint deformity is irreversible and causes serious functional impairment. Early and intensive treatment with close monitoring of the inflammation can slow the destructive disease and prevent function loss. However, it has been demonstrated that patients who are shown by conventional clinical and biochemical examination to have low disease activity or to be in remission can still have progressive joint damage. This demonstrates that current clinical/biochemical methods used in daily clinical practice are not sufficiently sensitive and other methods are required for the monitoring of disease activity and prognostication.

The presence of erosions (shown by X-ray examination) as well as anti-cyclic citrullinated peptide (anti-CCP) antibodies and bone marrow oedema (osteitis) on magnetic resonance imaging (MRI), are all independent predictors of subsequent radiographic progression. Bone marrow oedema has been shown to be the strongest independent predictor in early RA and MRI therefore has significant prognostic value.

It is therefore possible that supplementing conventional clinical and biochemical examinations of RA patients with MRI, and intensifying treatment where bone marrow oedema is present, will help reduce disease activity, avoid progressive joint damage and prevent function loss.

The current study is therefore based on the following hypothesis:

By supplementing conventional clinical and biochemical examination of RA patients with low disease activity/in remission with MRI and intensifying treatment in the case of sub-clinical inflammation as measured by the presence of bone marrow oedema, it is possible to prevent radiographic erosive progression, improve functional level and enable more patients to achieve clinical remission.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 18 years
  • RA according to ACR (American College of Rheumatology)/EULAR (European League Against Rheumatism) 2010 criteria.
  • Anti-CCP positivity
  • Erosions on conventional X-ray of hands, wrists and/or feet
  • No clinically swollen joints
  • DAS28 (4 variable, CRP) < 3.2
  • DMARD monotherapy treatment OR combination treatment, in the form of 2- or 3-drug therapy. If the patient is undergoing 3-drug therapy, at least one of the preparations must be administered at less than the "maximum inclusion dose"*
  • Unchanged anti-rheumatic treatment in the previous 6 weeks or more
  • No previous treatment with biological medication
  • No contra-indications for TNF-alpha-inhibiting treatment
  • No contra-indications for MRI
  • s-creatinine within normal range
  • Ability and willingness to give written and oral informed consent and fulfil the requirements of the study programme with reference to the protocol

    • Maximum "inclusion dose" is defined as: MTX 25 mg/week (or maximum tolerated dose if 25 mg/week is not tolerated), SSZ 2g/day (or maximum tolerated dose if 2 g/day is not tolerated) and HCQ 200 mg/day (or maximum tolerated dose if 200 mg/day is not tolerated)

Exclusion Criteria:

  • Previous or current biological treatment
  • Known intolerance to methotrexate treatment which means that the patient is not able to tolerate a minimum of MTX 7.5 mg (minimum dose).
  • DMARD 3-drug therapy at maximum tolerated/maximum "inclusion dose"*
  • I.m, intra-articular or i.v glucocorticoid administration ≤ 6 weeks prior to inclusion
  • Oral glucocorticoid administration > 5 mg/day
  • Changes in oral glucocorticoid dose < 3 months prior to inclusion
  • Myocrisin treatment
  • Affected liver enzymes > 2 x the upper limit of normal at the time of screening
  • Current and/or imminent wish to become pregnant
  • Contra-indications for TNF-alpha-inhibiting treatment
  • Contra-indications for MRI
  • Known alcohol/drug abuse
  • Inability to give informed consent
  • Inability to cooperate with the study programme due to physical or mental reasons
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01656278

Contacts
Contact: Kim Hørslev-Petersen, Professor +45 20236520 khorslev-petersen@gigtforeningen.dk
Contact: Signe Møller-Bisgaard, MD +45 28603187 s.moeller.bisgaard@gmail.com

Locations
Denmark
Køge Sygehus, Lykkebækvej 1, DK-4600, Køge, tel.: 47324700 Active, not recruiting
Køge, Copenhagen, Denmark, DK-4600
Dep. of Rheumatology Aarhus Hospital Recruiting
Aarhus, Denmark, 8600
Contact: Ellen Hauge, MD       ellen.hauge@aarhus.rm.dk   
Principal Investigator: Ellen Hauge, MD         
Sub-Investigator: Kristian Stengaard-Pedersen, Professor         
Dep. of Rheumatology Gentofte Hospital Recruiting
Copenhagen, Denmark, 2900
Contact: Ole Rintek Madsen, MD,PhD, DMSci       ole.rintek.madsen@regionh.dk   
Principal Investigator: Ole Rintek Madsen, MD, PhD, DMSci         
Dep. of Rheumatology Frederiksberg Hospital Recruiting
Copenhagen, Denmark, 2000
Contact: Karsten Asmussen, MD       karsten.heller.asmussen.01@regionh.dk   
Principal Investigator: Karsten Asmussen, MD         
Dep. of Rheumatology Glostrup Hospital Recruiting
Copenhagen, Denmark, 2600
Contact: Signe Møller-Bisgaard, MD    +45 28603187    s.moeller.bisgaard@gmail.com   
Contact: Mikkel Østergaard, Professor       mo@dadlnet.dk   
Principal Investigator: Signe Møller-Bisgaard, MD         
Dep. of Rheumatology King Christian X´Hospital for Rheumatic Diseases Recruiting
Graasten, Denmark, 6300
Contact: Kim Hørslev-Petersen, Professor       khorslev-petersen@gigtforeningen.dk   
Principal Investigator: Kim Hørslev-Petersen, Professor         
Dep. of rheumatology Odense Hospital Recruiting
Odense, Denmark, 5000
Contact: Hanne Lindegaard, MD, PhD       Hanne.Lindegaard@rsyd.dk   
Contact: Anne Friesgaard Chistensen, MD, PhD       anne.christensen@ouh.regionsyddanmark.dk   
Principal Investigator: Hanne Lindegaard, MD, PhD         
Sub-Investigator: Anne Friesgaard Christensen, MD, PhD         
Dep. of Rheumatology Silkeborg Hospital Recruiting
Silkeborg, Denmark, 8600
Contact: Jan Alexander Villadsen, MD       janvilla@rm.dk   
Contact: Tove Lorenzen, MD       tovelore@rm.dk   
Principal Investigator: Jan Alexander Villadsen, MD         
Dep. of Rheumatology Slagelse Hospital Recruiting
Slagelse, Denmark, 4200
Contact: Signe Møller-Bisgaard, MD    +45 28603187    s.moeller.bisgaard@gmail.com   
Contact: Bo Ejbjerg, MD, PhD       bjej@regionsjaelland.dk   
Principal Investigator: Signe Møller-Bisgaard, MD         
Sponsors and Collaborators
Professor of Rheumatology, MD, DMSci, Kim Horslev-Petersen
King Christian X´Hospital for Rheumatic Diseases
Slagelse Hospital
Glostrup University Hospital, Copenhagen
Abbott
Investigators
Principal Investigator: Kim Hørslev-Petersen, Professor King Christian X´Hospital for Rheumatic Diseases
Study Director: Signe Møller-Bisgaard, MD Dep. of Rheumatology, Slagelse Hospital
Study Chair: Mikkel Østergaard, Professor Dep. of Rheumatology, Glostrup Hospital
Study Chair: Bo Ejbjerg, MD, PhD Dep. of Rheumatology Slagelse Hospital
Study Chair: Merete Hetland, MD, PhD, DMSci Dep. of Rheumatology Glostrup Hospital
  More Information

No publications provided

Responsible Party: Professor of Rheumatology, MD, DMSci, Kim Horslev-Petersen, Professor of Rheumatology, MD, DMSci, King Christian X´Hospital for Rheumatic Diseases
ClinicalTrials.gov Identifier: NCT01656278     History of Changes
Other Study ID Numbers: IMAGINE-RA
Study First Received: July 5, 2012
Last Updated: March 11, 2014
Health Authority: Denmark: Ethics Committee

Keywords provided by King Christian X´Hospital for Rheumatic Diseases:
Arthritis, Rheumatoid/drug therapy
Arthritis, Rheumatoid/pathology
Disease Progression
Longitudinal Studies
Prospective Studies
Imaging, Magnetic Resonance
Remission Induction
Synovitis/immunology
Synovitis/pathology
Wrist Joint/pathology
Wrist Joint/physiopathology

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Disease Progression
Immune System Diseases
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on August 27, 2014