Efficacy of Cyclophosphamide Versus Methylprednisolone in Patients With Secondary Progressive Multiple Sclerosis (PROMESS)

March 14, 2012 updated by: University Hospital, Bordeaux

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 Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

138

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Bayonne, France, 64109
        • CH de la Cote Basque
      • Besançon, France, 25030
        • CHU Besançon
      • Bordeaux, France, 33076
        • Hôpital Pellegrin, Département de neurologie
      • Caen, France, 14033
        • CHU Caen
      • Clermont Ferrand, France, 63003
        • Hopital Gabriel Montpied
      • Créteil, France, 94010
        • AP HP Henri Mondor
      • Dijon, France, 21033
        • CHU Dijon
      • Lille, France, 59037
        • CHU Lille Hôpital Salengro
      • Limoges, France, 87042
        • CHU Limoges
      • Lomme, France, 59462
        • GHICL Hôpital St. Philibert
      • Lyon, France, 69394
        • (CHU Lyon) Hôpital neurologique
      • Marseille, France, 13385
        • Hôpital La Timone
      • Metz, France, 57038
        • (CHR Metz-Thionville) Hôpital Notre Dame de Bon Secours
      • Montpellier, France, 34295
        • (CHU Montpellier), Hôpital de Gui de Chauliac
      • Nancy, France, 54035
        • CHU Nancy Hôpital Central
      • Nantes, France, 44093
        • Hopital Guillaume Et Rene Laennec
      • Nice, France, 06002
        • CHU Nice Hôpital Pasteur
      • Nîmes, France, 30029
        • (CHU Nîmes) Hôpital Caremeau
      • Paris, France, 75019
        • Fondation Rothschild
      • Paris, France, 75970
        • (AP HP) Hôpital Tenon
      • Pau, France, 64046
        • Centre Hospitalier de Pau
      • Poissy, France, 78300
        • CHU de Poissy
      • Reims, France, 51092
        • (CHU Reims) Hôpital Robert Debré
      • Rennes, France, 35033
        • CHU Ponchaillou
      • Saint Michel, France, 16470
        • CH d'Angoulême Girac
      • Strasbourg, France, 67091
        • (CHRU Starsbourg) Hôpital civil

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Multiple sclerosis (MS) subjects (Mc Donald et al criteria),
  • Aged 18 to 65
  • Diagnosis of secondary progressive MS ( Lublin and Reingold criteria)
  • Progressive deterioration phase of at least 6 months and less than 4 years.
  • Reduction of walking capacity and increase EDSS not ascribed to consequence of relapses (at least 0.5 point) in the last 12 months
  • EDSS between 4.0 and 6.5 included
  • Female participating must use contraceptives while on study drug
  • Written informed consent
  • Patient protected by French social security system

Exclusion Criteria:

  • Others diseases interfering with MS or treatment
  • Recent history (within the previous 2 years) of drug or alcohol abuse.
  • Patients with psychiatric illnesses who are unable to provide written, informed consent prior to any testing under this protocol
  • Hemorrhagic cystitis
  • Pregnant or lactating women
  • Known allergy at cyclophosphamide, corticoids and in particular methylprednisolone
  • Persistent infectious diseases
  • Patients with bladder permanent catheterization
  • Known history of cardiac arrhythmia after methylprednisolone intravenous treatment
  • Abnormal screening/baseline blood tests exceeding any of the limits defined below : Hb < 9g/dl or Total white blood cell count less than 3 000/mm3 or lymphocytes count less than 900/ mm3 or Platelet count less than 125 000/mm3
  • Gastric or duodenal ulcer in evolution
  • Gut diverticulosis
  • Diabetes mellitus
  • Known history of active hepatitis (ASAT >3 X ULN)
  • Known history of renal failure (creatinine level > 180 µmol/L)
  • Psychosis
  • Current or past (< 3 months) participation in another drug trial
  • Prior use of cyclophosphamide, lymphoid irradiation, monoclonal antibodies anti CD4 or anti CD52 or anti-VLA-4 therapies, cladribine ou cyclosporine A
  • Other clinical types of MS : Secondary progressive phase evolving for more than 4 years ; Remittent type of MS without progression between relapses ; Primary progressive type of MS
  • Use of interferon beta, methotrexate or imurel in the month prior to study.
  • Treatment with intravenous monthly corticoids in the year prior to study.
  • Treatment with corticoids (3 to 5 days) in the 2 month prior to study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Cyclophosphamide
Drug: Cyclophosphamide (drug)
IV cyclophosphamide infusion administered every 4 weeks during 1 year and every 8 weeks during 1 year.
Active Comparator: 2
Methylprednisolone
Drug: Methylprednisolone (drug)
Control group : IV methylprednisolone infusion administered every 4 weeks during 1 year and every 8 weeks during 1 year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
every 4 weeks for one year, then every 8 weeks for one year

Secondary Outcome Measures

Outcome Measure
Time Frame
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
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)
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
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
all along the follow up period
Quality of life questionnaires
Time Frame: visit 2, 13(at one year) and 19 (at two years)
visit 2, 13(at one year) and 19 (at two years)
Disability self-assessment questionnaires
Time Frame: visite 2, 13 et 19
visite 2, 13 et 19

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bordeaux

Collaborators

Ministry of Health, France

Investigators

  • Principal Investigator: Bruno Brochet, Professor, University Hospital, Bordeaux, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2005

Primary Completion (Actual)

March 1, 2010

Study Completion (Actual)

March 1, 2012

Study Registration Dates

First Submitted

October 17, 2005

First Submitted That Met QC Criteria

October 17, 2005

First Posted (Estimate)

October 18, 2005

Study Record Updates

Last Update Posted (Estimate)

March 15, 2012

Last Update Submitted That Met QC Criteria

March 14, 2012

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9408-04
  • 2004-005

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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