Clinical Trial: Efficacy of Cyclophosphamide Versus Methylprednisolone in Patients With Secondary Progressive Multiple Sclerosis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Double-blind, Two-arm, Multicenter, Randomized Trial to Evaluate Efficacy of Cyclophosphamide Versus Methylprednisolone in Patients With Recent Secondary Progressive Multiple Sclerosis: P.R.OM.E.S.S

Brief Summary: 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. The primary objective of this trial is to evaluate the efficacy of IV cyclophosphamide as compared to IV methylprednisolone administered every 4 weeks during 1 year and every 8 weeks during 1 year, on the delay to confirmed disability deterioration as assessed by the Expanded Disability Status Scale (EDSS) in patients with secondary progressive multiple sclerosis. The secondary objectives are to evaluate safety, tolerability and efficacy at 2 years on the Multiple Sclerosis Functional Composite (MSFC), the percentage of patients with disability deterioration (EDSS) and the number of relapses. An intention-to-treat statistical analysis will be carried out.

Detailed Summary:

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
Sponsor: University Hospital, Bordeaux

Current 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) [ Time Frame: every 4 weeks for one year, then every 8 weeks for one year ]

Original 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

Current Secondary Outcome:

  • 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 ]
  • 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) ]
  • Number of MS relapses [ Time Frame: all along the follow up period ]
  • Proportion of patients with adverse events and delay of occurrence of adverse events [ Time Frame: all along the follow up period ]
  • Quality of life questionnaires [ Time Frame: visit 2, 13(at one year) and 19 (at two years) ]
  • Disability self-assessment questionnaires [ Time Frame: visite 2, 13 et 19 ]


Original Secondary Outcome:

  • - 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
  • - Disability autoquestionnaires
  • Main time of assessment : 2 years.


Information By: University Hospital, Bordeaux

Dates:
Date Received: October 17, 2005
Date Started: December 2005
Date Completion:
Last Updated: March 14, 2012
Last Verified: March 2012