Phase IV Study, Betaseron Versus Copaxone for Relapsing Remitting or CIS Forms of MS Using Triple Dose Gad 3 T MRI
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 4

Summary: 
      This is the first comparison of efficacy of Betaseron and Copaxone for treatment of relapsing
      forms of MS.
    

Detailed description: 
      We propose to perform a head to head comparison of Interferon beta and Copaxone for treatment
      of patients with CIS and RR forms of MS using acute changes on MRI as primary outcome. The
      study will be performed at the two clinical practice sites of the Multiple Sclerosis Center
      at University of Medicine and Dentistry New Jersey-New Jersey Medical School, One of the two
      FDA approved preparations of higher dose interferon beta (Betaseron) will be compared at
      standard dose every other day (QOD) 250 ug subcutaneously(SQ) with Copaxone at 20mg SQ daily
      (QD) in 70 to 80 patients. Although the current approved plan is to perform monthly MRIs for
      1 year followed by another MRI at 2 years, the protocol has been changed to continue
      performing monthly MRIs during the second year of the study for all patients who complete
      their first year and up to January 31, 2006 when the study will end. The study uses brain
      imaging with 3 Tesla MRI with triple dose Gadolinium for primary and secondary outcomes and
      several clinical and cognitive measures for secondary outcomes. The sample size was estimated
      to detect a 40-50% difference in the number of active MS lesions by MRI between the two arms
      at 1 year follow up, consistent with the primary outcome measure. The primary outcome measure
      is the number of "combined-active" lesions by monthly MRI at the conclusion of the study,
      which includes contrast enhancing lesions and non-enhancing lesions on long Time repetition
      (TR) scans that have appeared since the most recent examination. Several secondary MRI
      outcome measures are studied in addition to the number of enhancing lesions and the number of
      new lesions on long TR images. We will examine the number of patients who remain
      "combined-active disease-free" for the duration of the study and the number of
      "combined-active disease-free" scans. Apart from these traditional methods of analysis by a
      reader who will be blinded to patient clinical status and therapy, objective volumetric
      analysis will be carried out. Making use of both automated and manual techniques, we will
      determine the overall burden of disease (the volume of lesions on long TR scans), the burden
      of active disease (the volume of brain enhancement) and the burden of chronic disease (the
      volume of lesions that are markedly hypointense on T1). Another MRI outcome measures will be
      detection of diffusion anisotropy differences, MR spectroscopy, and magnetization transfer
      ratio as summarized in Appendix 5. These new techniques have shown promise for detecting
      disease that cannot be detected with conventional MRI (13, 37).

      In addition to MRI, several clinical and cognitive outcome measures will be used for
      secondary analysis. These include the number and severity of relapses measured by different
      methods, and change in disability measured by the Expanded Disability Status Scale (EDSS),
      the Neurological Rating Scale, and the Multiple Sclerosis Functional Composite (MSFC). The
      cognitive measures will be the subject's neurocognitive function measured by standard
      neurocognitive examination obtained by a licensed neuropsychologist and the Cognitive
      Stability Index (CSI), a novel Internet-based test of cognitive function in addition to the
      Paced Auditory Serial Addition Test (PASAT),which is a component of the MSFC.
    

Intervention name(s): Betaseron; Copaxone
Intervention type(s): Drug; Drug
Intervention description(s): Betaseron 250 micrograms injected SQ every other day; Copaxone 20 mg injected SQ every day (glatiramer acetate)
Other intervention name(s): Betaseron 250 mcg SQ every other day; Intaferon beta 1 b; Copaxone 20 mg injected SQ every day (glatiramer acetate)
Intervention MeSH terms: Glatiramer Acetate; Interferon beta-1b; (T,G)-A-L
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Multiple Sclerosis; Brain; Betaseron; Copaxone; MRI