Effect of Interferon Beta-1a (Avonex®) on Changes of Non-conventional MRI Measures in Patients With MS
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Observational

Summary: 
      Phase IV open label, single-blind study, post-marketing, 1-year MRI observational study
      evaluating effect of Avonex® monotherapy (6.0 MIU administered i.m. each week) on the
      year-to-year changes in two annual measures-magnetization transfer imaging and
      diffusion-weighted imaging in patients with either relapsing-remitting (RR) or
      secondary-progressive (SP) multiple sclerosis (MS). One hundred fifty (150) patients with RR
      and SP MS-followed at the Jacobs Neurological Institute, University at Buffalo, Buffalo
      NY-who satisfy both inclusion and exclusion criteria will be included. They will be assessed
      at baseline and at 12 months with MRI and clinical examinations.
    

Detailed description: 
      1.1. Protocol Title: Effect of Interferon beta-1a (Avonex®) on changes of non-conventional
      MRI measures in patients with relapsing-remitting and secondary-progressive multiple
      sclerosis.

      1.2. Study rationale: Only a few longitudinal studies have investigated the effect of
      disease-modifying (DMT) on annual changes of non-conventional magnetic resonance imaging
      (MRI) measures, such as magnetization transfer imaging (MTI) in patients with multiple
      sclerosis (MS). In a previous study, the effect of interferon beta-1a (Avonex®) administered
      IM each week was investigated on the evolution of monthly magnetization transfer ratio (MTR)
      within new gadolinium (Gd)-enhancing lesions in patients with very early relapsing-remitting
      (RR) MS. Eight untreated patients with RRMS who completed up to 14 monthly brain MRI sessions
      elected to initiate treatment with Avonex®. The difference between MTR at appearance of 47
      new Gd+ lesions before treatment versus 23 new Gd+ lesions during treatment with Avonex® was
      not significant. However, after appearance of new Gd+ lesions, the rate of increase in MTR
      (index of remyelination) was faster during therapy (p = 0.037). This study indicated that MTR
      abnormalities within new Gd+ lesions may evolve at a slower rate during treatment with
      Avonex® than before initiating therapy and that Avonex® may promote resolution of new Gd+
      lesions. However, although this study yielded some positive results, it was not empowered to
      establish whether Avonex® may have a real treatment effect on lesion recovery. Moreover, in
      that study, the effect of Avonex® was not investigated on changes in normal appearing brain
      tissue (NABT) over time.

      1.3. Study Aims: Aim 1. To define the effect of interferon beta-1 (Avonex®) monotherapy (6.0
      MIU administered i.m. each week) on the year-to-year changes in two annual measures-MTI and
      diffusion-weighted imaging (DWI)-in patients with either RR or secondary-progressive (SP) MS.

      Aim 2. To explore differences in the progression of these two non-conventional MRI measures
      between patients who do and do not develop significant brain atrophy, hyperintense T2- and
      hypointense T1 (black holes) lesion volume (LV) progression during the same 12 months.

      Aim 3. To investigate differences in the progression of non-conventional MRI measures between
      patients who respond or not respond to Avonex® monotherapy during the same 12 months.

      1.4. Design and Methods: 1.4.1. Study outline: Phase IV open label, single-blind study,
      post-marketing, 1-year MRI observational study evaluating effect of Avonex® monotherapy (6.0
      MIU administered i.m. each week) on the year-to-year changes in two annual measures-MTI and
      DWI-in patients with either RR or SP MS.

      One hundred fifty (150) patients with RR and SP MS-followed at the Jacobs Neurological
      Institute, University at Buffalo, Buffalo NY-who satisfy both inclusion and exclusion
      criteria will be treated with Avonex® monotherapy. They will be assessed at baseline and at
      12 months with MRI and clinical examinations. These patients are part of a larger cohort of
      MS patients (1000) who are on Avonex® mono- or combination therapy and are being routinely
      followed at the Jacobs Neurological Institute.

      MRI assessment will include detailed conventional and non-conventional protocol. Neurological
      assessment included Kurtzke Expanded Disability Status Scale (EDSS) score and evaluation of
      relapses.

      1.4.2. Outcome measures: The primary outcome of the study is to measure the effect of Avonex®
      monotherapy on changes in lesional MTR, whole brain (WB) MTR, normal appearing GM (NAGM) MTR
      and normal appearing WM (NAWM) MTR, as well as in WB mean diffusivity (MD) and entropy, as
      measured by the 1-year changes from baseline.

      The secondary outcomes will include measurement of brain parenchymal fraction (BPF), GM
      fraction (GMF), WM fraction (WMF), T1- and T2- (LV), number and volume of Gd-enhancing
      lesions and evaluation of annual relapse rate and EDSS.
    

Intervention name(s): Avonex® monotherapy (6.0 MIU administered i.m. each week)
Intervention type(s): Drug
Intervention MeSH terms: Interferon beta-1a
Time perspective: Other
Keywords: MTI, DWI, Avonex, MRI