• Delay to disability deterioration as assessed by the Expanded Disability Status Scale (EDSS: 0.5 or 1 point increase, depending on baseline score) [ Time Frame: every 4 weeks for one year, then every 8 weeks for one year ] [ Designated as safety issue: No ]
  

• Proportion of patients with disability deterioration (EDSS: 0.5 or 1 point increase, depending on baseline score) [ Time Frame: every month during one year then every two months during the 2nd year ] [ Designated as safety issue: No ]
  
• Multiple Sclerosis Functional Composite (MSFC) and the Z scores of MSFC three components [ Time Frame: Visit number 1, 2, 13(at one year),19 (at two years) and 20 (last visit) ] [ Designated as safety issue: No ]
  
• Number of MS relapses [ Time Frame: all along the follow up period ] [ Designated as safety issue: No ]
  
• Proportion of patients with adverse events and delay of occurrence of adverse events [ Time Frame: all along the follow up period ] [ Designated as safety issue: Yes ]
  
• Quality of life questionnaires [ Time Frame: visit 2, 13(at one year) and 19 (at two years) ] [ Designated as safety issue: No ]
  
• Disability self-assessment questionnaires [ Time Frame: visite 2, 13 et 19 ] [ Designated as safety issue: No ]
  

Background

Preliminary not-controlled clinical studies of the efficacy of monthly intravenous cyclophosphamide administration in secondary progressive multiple sclerosis reported encouraging results, but no randomized controlled trial has been conducted so far. A slight efficacy of Methylprednisolone has been reported in this indication.

Objectives

The primary objective is to evaluate the efficacy of IV cyclophosphamide on the prevention of disability deterioration in patients with secondary progressive multiple sclerosis.

The secondary objectives are to evaluate safety, tolerability and efficacy of IV cyclophosphamide on the Multiple Sclerosis Functional Composite (MSFC) and the number of relapses.

Study design

Randomized double-blind two-arm controlled trial.

Intervention

Experimental group : IV cyclophosphamide infusion administered every 4 weeks during 1 year and every 8 weeks during 1 year.

Control group : IV methylprednisolone infusion administered every 4 weeks during 1 year and every 8 weeks during 1 year.

Outcomes

Primary outcome : delay to disability deterioration as assessed by the Expanded Disability Status Scale (EDSS: 0.5 or 1 point increase, depending on baseline score) evaluated every 4 weeks for one year, then every 8 weeks for one year.

Secondary outcomes : proportion of patients with disability deterioration (EDSS: 0.5 or 1 point increase, depending on baseline score), Multiple Sclerosis Functional Composite (MSFC) and the Z scores of MSFC three components, number of MS relapses, proportion of patients with adverse events and delay of occurrence of adverse events, quality of life questionnaires.

• Quality of life questionnaires
• Disability self-assessment questionnaires Main time of assessment : 2 years.

Sample size

360 patients

Statistical analysis

Intention-to-treat analysis.