Study to Compare the Clinical and Radiological Efficacy of 625 mg Versus 1250 mg of Oral Methylprednisolone in Patients With Multiple Sclerosis in Relapse

Multicenter, Randomized, Double-blind Clinical Trial to Compare the Clinical and Radiological Efficacy of 625 mg Versus 1250 mg of Oral Methylprednisolone in Patients With Multiple Sclerosis in Relapse.

The investigators plan to carry out a multicenter randomized clinical trial and MRI study of high-dose oMP (1250mg/day for 3 days) versus lower-high dose oMP (625mg/day for 3 days) and demonstrated that lower-high dose of oMP is as effective as a higher-high dose of oMP in acute relapse of multiple sclerosis (MS). If it is shown, our purpose is to promote this therapeutic regimen because it is safer for the patient (less adverse effects) and less costly to the healthcare system.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Methylprednisolone 1250 mg/24h x3 days; Drug: Oral Methylprednisolone 625 mg/24h x3 days

Detailed Description

DESIGN: Phase IV clinical trial, multicentre, randomized and double blind, active drug controlled and parallel groups. Patients will be randomised to a high dose of oMP vs a lower-high dose of oral Methylprednisolone (oMP).

SETTING: 9 MS Units from 9 hospitals of the public health system with extensive experience in treating patients with MS and design and participation in clinical trials.

PROCEDURES:

After signing the informed consent, the inclusion and exclusion criteria specific to the study will be checked. The diagnostic test will take place prior to administration of study medication and will include medical history, neurological examination (EDSS measurement) taking of vital signs (blood pressure, heart rate and body temperature) and MRI. Concomitant medication will be checked. Patients will be instructed about the requirements during the study.

The trial medication will be provided to the patient in the medical office (day 1 of the study), where the patient will remain until the intake. This action will be repeated the following 2 days. The latency period from the beginning of the relapse until the start of treatment will be registered. The questionnaires of tolerance will be completed.

Day 1 will be defined as the first day on which first dose of oMP is administered.

Once given the treatment under study, the adverse events reported spontaneously or after question will be collected.

There will be follow-up visits at 7 and 28 days, and 3 months after initiation of treatment. At baseline, prior to drug administration, and on days 7 and 28 after initiation of treatment, a brain MRI with and without contrast will be performed. In case of adverse events or laboratory abnormalities, the patients could have an accessory follow-up visits until resolution.

Randomization will be performed on the day of administration (day 1)

The treatments are:

Group A: Methylprednisolone 1250 mg / day orally for 3 days Group B: Methylprednisolone 625 mg / day orally for 3 days

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

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial de Barcelona
  • Barcelona, Spain, 08034
    • Hospital de Mataro
  • Barcelona, Spain
    • Hospital de Sant Joan Despí Moisès Broggi
  • Girona, Spain, 17007
    • Hospital Universitari de Girona Dr. Josep Trueta
  • Lleida, Spain, 25198
    • Hospital Universitari Arnau de Vilanova de Lleida
  • Tarragona, Spain
    • Hospital de Sant Pau i Santa Tecla
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias I Pujol de

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. Relapsing-remitting MS (Mc Donald criteria 2010) regardless being under immunomodulatory treatment
2. EDSS (previous to relapse) between 0 and 5

3. MS relapse of moderate intensity (EDSS increase from 1 to 2.5 points) or severe intensity (EDSS increase > 3 points)

   • If EDSS previous relapse is available:

     • optic neuritis, myelitis or brainstem relapse: the EDSS should increase of 1 point in visual, pyramidal or brainstem system function
     • relapse in other location or uncertain location: the EDSS should increase at least 1 point

   • If EDSS previous relapse is not available:

     • optic neuritis, myelitis or brainstem relapse: the visual, pyramidal or brainstem system function should be > 2 points.
     • relapse in other location or uncertain location: EDSS should be > 2 points
4. Recent clinical relapse onset (<15 days) without fever
5. One month of clinical stability prior to relapse
6. Signed informed consent
7. Capacity to ingest the medication.

Exclusion Criteria:

1. Doubts about the diagnosis of multiple sclerosis
2. First episode of inflammatory neurological disease
3. Secondary progressive MS or primary progressive MS
4. Symptoms with lasted less than 24 hours of evolution
5. Any degree of subjective or objective remission
6. Treatment with corticosteroids during the previous 30 days
7. Patients with immunosuppressive treatment (azathioprine, mitoxantrone, cyclophosphamide) or Natalizumab or Fingolimod
8. Pregnancy or breastfeeding women or women of childbearing potential not using contraceptive measures
9. Diseases with a contraindication of treatment with corticosteroids
10. History of serious adverse reaction or hypersensitivity to drugs related to study medication
11. Patients who could not be regular MRI, not collaborators or who requires anesthesia.
12. Lactose intolerance
13. Patients with allergies to contrast used in MRI
14. Patients with renal impairment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: oMP 1250 mg: Group A; Methylprednisolone 1250 mg/24h x3 days	Drug: Methylprednisolone 1250 mg/24h x3 days; Oral Methylprednisolone 1.250 mg daily, over 1 hour and during 3 consecutive days. 13 capsules will be administered (12 capsules of 100 mg and 1 capsule of 50 mg); Other Names: Group A
Active Comparator: oMP 625 mg: Group B; Methylprednisolone oral 625 mg/24h x3 days	Drug: Oral Methylprednisolone 625 mg/24h x3 days; Oral Methylprednisolone 625 mg daily, over 1 hour and during 3 consecutive days. 13 capsules will be administered (6 capsules of 100 mg, 1 capsule of 25 mg and 6 capsules of placebo with the same appearance of capsules of 100 mg); Other Names: Group B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disability scale of Kurtzke EDSS score	up to day 91

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events / tolerability	Baseline and day 29
Disability scale of Kurtzke EDSS score	Baseline and day 8
The number and volume of active lesions (measured by the T2 or gadolinium enhancement), the number of new active lesions and the percentage of active lesions at baseline that becomes black holes	day -1 and day 29
Adverse events / tolerability	Baseline and day 8
Questionnaire MSQOL-54	Baseline and day 8
Questionnaire MSQOL-54	Baseline and day 29

Collaborators and Investigators

• Sponsor: Germans Trias i Pujol Hospital

Publications and helpful links

General Publications

• Hervas-Garcia JV, Ramio-Torrenta L, Brieva-Ruiz L, Batlle-Nadal J, Moral E, Blanco Y, Cano-Orgaz A, Presas-Rodriguez S, Torres F, Capellades J, Ramo-Tello C. Comparison of two high doses of oral methylprednisolone for multiple sclerosis relapses: a pilot, multicentre, randomized, double-blind, non-inferiority trial. Eur J Neurol. 2019 Mar;26(3):525-532. doi: 10.1111/ene.13851. Epub 2018 Nov 16.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: January 11, 2013
• First Submitted That Met QC Criteria: November 18, 2013
• First Posted (Estimate): November 19, 2013

Study Record Updates

• Last Update Posted (Estimate): June 3, 2016
• Last Update Submitted That Met QC Criteria: June 2, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: EDSS; gadolinium; Multiple sclerosis relapse; oral 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: oral-CORTEM; 2012-001965-34 (EudraCT Number)