Trial record 2 of 51 for:    "Multiple Sclerosis, Chronic Progressive"

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

This study has been completed.
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT00241254
First received: October 17, 2005
Last updated: March 14, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis, Chronic Progressive
Drug: Cyclophosphamide (drug)
Drug: Methylprednisolone (drug)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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 Study

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 138
Study Start Date: December 2005
Study Completion Date: March 2012
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00241254

Locations
France
CH de la Cote Basque
Bayonne, France, 64109
CHU Besançon
Besançon, France, 25030
Hôpital Pellegrin, Département de neurologie
Bordeaux, France, 33076
CHU Caen
Caen, France, 14033
Hôpital Gabriel Montpied
Clermont Ferrand, France, 63003
AP HP Henri Mondor
Créteil, France, 94010
CHU Dijon
Dijon, France, 21033
CHU Lille Hôpital Salengro
Lille, France, 59037
CHU Limoges
Limoges, France, 87042
GHICL Hôpital St. Philibert
Lomme, France, 59462
(CHU Lyon) Hôpital neurologique
Lyon, France, 69394
Hôpital La Timone
Marseille, France, 13385
(CHR Metz-Thionville) Hôpital Notre Dame de Bon Secours
Metz, France, 57038
(CHU Montpellier), Hôpital de Gui de Chauliac
Montpellier, France, 34295
CHU Nancy Hôpital central
Nancy, France, 54035
Hôpital Guillaume et René Laënnec
Nantes, France, 44093
CHU Nice Hôpital Pasteur
Nice, France, 06002
(CHU Nîmes) Hôpital Caremeau
Nîmes, France, 30029
(AP HP) Hôpital Tenon
Paris, France, 75970
Fondation Rothschild
Paris, France, 75019
Centre Hospitalier de Pau
Pau, France, 64046
CHU de POISSY
Poissy, France, 78300
(CHU Reims) Hôpital Robert Debré
Reims, France, 51092
CHU Ponchaillou
Rennes, France, 35033
CH d'Angoulême Girac
Saint Michel, France, 16470
(CHRU Starsbourg) Hôpital civil
Strasbourg, France, 67091
Sponsors and Collaborators
University Hospital, Bordeaux
Ministry of Health, France
Investigators
Principal Investigator: Bruno Brochet, Professor University Hospital, Bordeaux, France
Study Chair: Paul Perez, Dr University Hospital, Bordeaux, France
  More Information

No publications provided

Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT00241254     History of Changes
Other Study ID Numbers: 9408-04, 2004-005
Study First Received: October 17, 2005
Last Updated: March 14, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
Multiple Sclerosis, Chronic Progressive
Cyclophosphamide
Methylprednisolone
Randomized Controlled Trials
Double-Blind Study

Additional relevant MeSH terms:
Multiple Sclerosis, Chronic Progressive
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Cyclophosphamide
Methylprednisolone Hemisuccinate
Prednisolone
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on September 18, 2014