Oral Corticotherapy in Megadoses to Treat Multiple Sclerosis During Relapse

Multicenter, Randomized, Double Blind, Clinical Trial to Compare the Clinical and Radiological Efficacy of Equivalent Doses of Methylprednisolone Administered Orally or Intravenously in Patients With Multiple Sclerosis During Relapse

This is a phase IV, multicenter, randomized, double blind clinical trial. The investigators will study 48 patients with remitting relapsing multiple sclerosis (MS) experiencing moderate or severe attack receiving immunomodulatory therapy or not. Patients will be randomly assigned to one of the two groups.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: methylprednisolone; Drug: methylprednisolone; Drug: Placebo

Detailed Description

This is a multicenter, randomized, double blind clinical trial to test whether oral methylprednisolone (MP) is not inferior to intravenous methylprednisolone for the treatment of multiple sclerosis (MS) relapse in terms of clinical and radiological efficacy.

Patients will be randomly assigned to one of the following two groups.

Group A: methylprednisolone 1.000 mg/day intravenous administered during three days + placebo of methylprednisolone orally administered

Group B: methylprednisolone 1.250 mg/day orally administered during three days + placebo of methylprednisolone intravenously administered.

Clinical visits will be conducted at 7, 28 and 90 days after treatment starting.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Barcelona, Spain, 08034
    • Hospital de Mataro
  • Girona, Spain, 17007
    • Hospital Dr. Trueta
  • Lleida, Spain, 25198
    • Hospital Arnau de Vilanova
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Germans Trias I Pujol Hospital
  • Girona
    • Figueres, Girona, Spain, 17600
      • Hospital de Figueres

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. To have been diagnosed MS Remittent Recurrent according to Mc Donald 20052 criteria.
2. To have an EDSS between 0 and 5 before the relapse.
3. The symptoms have begun after at least one month of previous stability.
4. The symptoms have started maximum 15 days before the inclusion.
5. The patient is capable of having an adequate communication with the investigator and to carry out with the clinical trial requisites.
6. To be or not to be with allowed immunomodulatory therapy (IFN-B /AG).
7. To be capable and to be willing to ingest the medication.

Exclusion Criteria:

1. First inflammatory neurological episode (relapse).
2. Multiple sclerosis secondary progressive or primary progressive.
3. The symptoms have gone on for less than 24 hours.
4. To be in treatment or have been treated with corticoids during the three months before.
5. Patients in treatment with immunosuppressors (azathioprine, mitoxantrone, ciclofosfamide...)
6. Pregnancy or breastfeeding or women in fertile age who don't use contraceptives measurements.
7. Illnesses with contraindication treatment with corticoids.
8. Antecedents of serious adverse effects or hypersensitive to related study medication.
9. Patients who wouldn´t be able to perform periodic RMN explorations, patients who are not collaborative or who need anesthesia.
10. Patients with intolerance to lactose.
11. Patients with allergy to contrast used in RMN.
12. Patients with chronic kidney disease.
13. Patients in treatment with natalizumab.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 1; methylprednisolone 1.000 mg/day intravenous administration during three days + placebo of methylprednisolone orally administered	Drug: methylprednisolone; methylprednisolone 1.000 mg/day intravenous administration during three days; Other Names: Group A; Drug: methylprednisolone; methylprednisolone 1.250 mg/day orally administered during three days; Other Names: Group B; Drug: Placebo; Placebo of methylprednisolone administered intravenously (Arm 2) or orally (Arm 1); Other Names: Group B; Group A
EXPERIMENTAL: 2; methylprednisolone 1.250 mg/day orally administered during three days + placebo of methylprednisolone intravenous administered	Drug: methylprednisolone; methylprednisolone 1.000 mg/day intravenous administration during three days; Other Names: Group A; Drug: methylprednisolone; methylprednisolone 1.250 mg/day orally administered during three days; Other Names: Group B; Drug: Placebo; Placebo of methylprednisolone administered intravenously (Arm 2) or orally (Arm 1); Other Names: Group B; Group A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in the punctuation of diana functional system score corresponding to in relapse of optic neuritis, trunk's syndrome and myelitis	day 28
Change in EDSS in patients who present a relapse from different type or unknown topography	day 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in the punctuation in each group	between days 7 and 0
Percentage of patients who improve, get worse and keep stable	days 7 and 28

Collaborators and Investigators

• Sponsor: Germans Trias i Pujol Hospital

Publications and helpful links

General Publications

• Ramo-Tello C, Tintore M, Rovira A, Ramio-Torrenta L, Brieva L, Saiz A, Cano A, Carmona O, Hervas JV, Grau-Lopez L. Baseline clinical status as a predictor of methylprednisolone response in multiple sclerosis relapses. Mult Scler. 2016 Jan;22(1):117-21. doi: 10.1177/1352458515590648. Epub 2015 Jun 25.
• Grau-Lopez L, Teniente-Serra A, Tintore M, Rovira A, Ramio-Torrenta L, Brieva L, Saiz A, Cano A, Carmona O, Hervas JV, Martinez-Caceres EM, Ramo-Tello C. Similar biological effect of high-dose oral versus intravenous methylprednisolone in multiple sclerosis relapses. Mult Scler. 2015 Apr;21(5):646-50. doi: 10.1177/1352458514546786. Epub 2014 Aug 21.
• Ramo-Tello C, Grau-Lopez L, Tintore M, Rovira A, Ramio i Torrenta L, Brieva L, Cano A, Carmona O, Saiz A, Torres F, Giner P, Nos C, Massuet A, Montalban X, Martinez-Caceres E, Costa J. A randomized clinical trial of oral versus intravenous methylprednisolone for relapse of MS. Mult Scler. 2014 May;20(6):717-25. doi: 10.1177/1352458513508835. Epub 2013 Oct 21.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (ACTUAL): November 1, 2010
• Study Completion (ACTUAL): January 1, 2011

Study Registration Dates

• First Submitted: September 16, 2008
• First Submitted That Met QC Criteria: September 16, 2008
• First Posted (ESTIMATE): September 17, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): June 2, 2011
• Last Update Submitted That Met QC Criteria: June 1, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: relapse; multiple sclerosis; methylprednisolone
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease Attributes; Multiple Sclerosis; Sclerosis; Recurrence; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: CORTEM; 2007-000888-15