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

Multiple Sclerosis Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01986998
• Other study ID #: oral-CORTEM
• Secondary ID: 2012-001965-34
• Status: Completed
• Phase: Phase 4
• First received: January 11, 2013
• Last updated: June 2, 2016
• Start date: October 2013
• Est. completion date: March 2016

Study information

• Verified date: June 2016
• Source: Germans Trias i Pujol Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: March 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 59 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

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)
• 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)

Locations

Country	Name	City	State
Spain	Hospital Universitari Germans Trias I Pujol de	Badalona	Barcelona
Spain	Hospital Clinic I Provincial de Barcelona	Barcelona
Spain	Hospital de Mataró	Barcelona
Spain	Hospital de Sant Joan Despí Moisés Broggi	Barcelona
Spain	Hospital Del Mar	Barcelona
Spain	Hospital Universitari de Girona Dr. Josep Trueta	Girona
Spain	Hospital Universitari Arnau de Vilanova de Lleida	Lleida
Spain	Hospital de Sant Pau I Santa Tecla	Tarragona

Sponsors (1)

Lead Sponsor	Collaborator
Germans Trias i Pujol Hospital

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disability scale of Kurtzke EDSS score		up to day 91	Yes
Secondary	Adverse events / tolerability		Baseline and day 29	Yes
Secondary	Disability scale of Kurtzke EDSS score		Baseline and day 8	Yes
Secondary	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	No
Secondary	Adverse events / tolerability		Baseline and day 8	Yes
Secondary	Questionnaire MSQOL-54		Baseline and day 8	No
Secondary	Questionnaire MSQOL-54		Baseline and day 29	No