Oral Prednisone Taper Versus Placebo for the Treatment of Acute Relapses in Multiple Sclerosis

NCT ID: NCT01411514

Last Updated: 2015-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-08-31

Study Completion Date

2015-01-31

Brief Summary

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The management of MS-patients requires treatment with immune-modifying or immune-suppressive agents to prevent new relapses and progression of disability. Several studies have evaluated the effect of steroid treatment on clinical recovery after an acute relapse. An important unanswered clinical question is, whether or not an oral tapering dose of corticosteroids offers any additional advantage over intravenous methylprednisolone alone in improving neurologic recovery as well as safety and tolerability after a relapse.

This study aims to compare the efficacy, tolerability and safety of tapering doses of oral prednisone and placebo after short-term high-dose i.v. methylprednisolone on the recovery from an acute relapse in patients with clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RR-MS) and primary (PP-MS) or secondary progressive multiple sclerosis (SP-MS) with superimposed relapses.

Patients will be treated during 25 days with de-escaling doses of prednisone or placebo.

The primary analysis will test whether placebo is equivalent to oral prednisone taper on the recovery status as measured by EDSS change from baseline to 3 months after baseline.

Detailed Description

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The purpose of this double-blind, randomised, placebo-controlled, prospective, parallel group, single centre study is to evaluate the effect of tapering oral doses of prednisone or placebo taken during 25 days following short-term high-dose i.v. methylprednisolone on the outcome of a relapse in patients with CIS; RR-MS, PP-MS or SP-MS with superimposed relapses. The primary objective is to assess and compare the recovery status in both patient groups 3 months after baseline by means of Expanded Disability Status Scale (EDSS). Secondary objectives are the assessments of clinical parameters at the end of oral treatment, 6, 9 months after baseline, of MRI markers, of mental and cognitive status, quality of life and fatigue at the end of oral treatment, 3 and 6 months after baseline in both patient groups.

After standard treatment of an acute clinical relapse with high dose, short term i.v. methyprednisolone patients will be randomised to one of the two treatment arms. Patients allocated to prednisone will be treated with tapering oral doses during 25 days. The initial dose of 60 mg will be reduced twice by 20 mg, than by 10 and 5 mg. Each dose regimen will be taken during 5±2 days. Patients randomised to placebo will receive placebo treatment during 25 days.

Conditions

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Multiple Sclerosis

Keywords

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Relapsing remittent multipse sclerosis Secondary progressive multiple sclerosis Clinically isolated syndrome Primary progressive multiple sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Prednisone

Group Type EXPERIMENTAL

Prednisone

Intervention Type DRUG

Tablets, 60 mg od p.o. for 5 days, followed by 40 mg o.d. p.o. for 5 days, 20 mg o.d. p.o. for 5 days, 10 mg o.d. p.o. for 5 days, 5 mg o.d. p.o. for 5 days

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo tablets. They will be administered during 25 days

Interventions

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Prednisone

Tablets, 60 mg od p.o. for 5 days, followed by 40 mg o.d. p.o. for 5 days, 20 mg o.d. p.o. for 5 days, 10 mg o.d. p.o. for 5 days, 5 mg o.d. p.o. for 5 days

Intervention Type DRUG

Placebo

Placebo tablets. They will be administered during 25 days

Intervention Type DRUG

Other Intervention Names

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Prednison Axapharm Placebo tablets

Eligibility Criteria

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Inclusion Criteria

* female or male
* aged between 18 and 80 years;
* with relapsing forms of multiple sclerosis diagnosed according to McDonald's criteria, including RR-MS and relapsing SP-MS, CIS, PP;
* with EDSS score between 0 and 8;
* experiencing an acute relapse with a documented clinical worsening of at least one point of the EDSS scale or a worsening of at least 2 points in one of the EDSS functional systems;
* having agreed to have MRI and having already received at least one enhanced MRI before study procedures without major side effects;
* having agreed to adhere to the study procedures;
* having signed the written informed consent form.

Exclusion Criteria

* secondary progressive MS without superimposing relapses;
* primary progressive MS without superimposed relapses;
* patients suffering from any clinical condition contraindicated for steroid, in particular

* Systemic fungal infection
* Severe osteoporosis
* Uncontrolled hypertension or congestive heart failure.
* Existing or previous history of severe affective disorders (especially previous steroid psychosis).
* Diabetes mellitus
* History of tuberculosis
* Glaucoma
* Previous corticosteroid-induced myopathy
* Liver failure or cirrhosis
* Renal insufficiency
* Active epilepsy
* Peptic ulceration
* Fresh intestinal anastomoses
* Predisposition to thrombophlebitis
* Abscess or other pyogenic infections
* Diverticulitis
* Myasthenia gravis
* Ocular herpes simplex
* Hypothyroidism
* Recent myocardial infarction
* Kaposi's sarcoma;
* any disease other than multiple sclerosis that would better explain the patient's signs and symptoms;
* women of potential childbearing without active contraceptive methods;
* pregnancy (urine pregnancy test at baseline visit) or breast feeding;
* history of affective disorders;
* history of attempted suicide or current suicidal ideas;
* medical or psychiatric conditions that compromise the ability to give informed consent, to comply with the protocol, or to complete the study;
* inability, in the opinion of the principal investigator or staff, to comply with protocol requirements for the duration of the study;
* known hypersensitivity to prednisone or excipients of the study medications;
* any contraindication for concomitant medications;
* any contraindication for MRI or contrast administration;
* a history of drug abuse in the 6 months prior to screening;
* use of steroids during the previous 30 days (disease-modifying therapies for the treatment of MS are allowed);
* treatment with drugs that might interfere with the evaluation of study drugs during the study protocol (see Section 4.2.2);
* likelihood of requiring treatment during the study period with drugs not permitted by the study protocol;
* participation in an other clinical trial within 30 days prior to entry in this study or current participation in another trial.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ente Ospedaliero Cantonale, Ticino, Switzerland

OTHER

Sponsor Role collaborator

Claudio Gobbi

OTHER_GOV

Sponsor Role lead

Responsible Party

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Claudio Gobbi

Dr. med.

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Claudio Gobbi, MD

Role: PRINCIPAL_INVESTIGATOR

Neurocenter of Southern Switzerland

Claudio Gobbi, MD

Role: STUDY_DIRECTOR

Neurocenter of Southern Switzerland

Locations

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Osepdale Civico

Lugano, Canton Ticino, Switzerland

Site Status

Countries

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Switzerland

References

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Sellebjerg F, Barnes D, Filippini G, Midgard R, Montalban X, Rieckmann P, Selmaj K, Visser LH, Sorensen PS; EFNS Task Force on Treatment of Multiple Sclerosis Relapses. EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses. Eur J Neurol. 2005 Dec;12(12):939-46. doi: 10.1111/j.1468-1331.2005.01352.x.

Reference Type BACKGROUND
PMID: 16324087 (View on PubMed)

Burton JM, O'Connor PW, Hohol M, Beyene J. Oral versus intravenous steroids for treatment of relapses in multiple sclerosis. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD006921. doi: 10.1002/14651858.CD006921.pub2.

Reference Type BACKGROUND
PMID: 19588409 (View on PubMed)

Martinelli V, Rocca MA, Annovazzi P, Pulizzi A, Rodegher M, Martinelli Boneschi F, Scotti R, Falini A, Sormani MP, Comi G, Filippi M. A short-term randomized MRI study of high-dose oral vs intravenous methylprednisolone in MS. Neurology. 2009 Dec 1;73(22):1842-8. doi: 10.1212/WNL.0b013e3181c3fd5b.

Reference Type BACKGROUND
PMID: 19949030 (View on PubMed)

Perumal JS, Caon C, Hreha S, Zabad R, Tselis A, Lisak R, Khan O. Oral prednisone taper following intravenous steroids fails to improve disability or recovery from relapses in multiple sclerosis. Eur J Neurol. 2008 Jul;15(7):677-80. doi: 10.1111/j.1468-1331.2008.02146.x. Epub 2008 May 6.

Reference Type BACKGROUND
PMID: 18459972 (View on PubMed)

Related Links

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http://www.eoc.ch/

Related information to the institution

http://www.multiplesklerose.ch/

Non profit organisazion that supports multiple sclerosis patients

Other Identifiers

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EOC.NC.10.04

Identifier Type: -

Identifier Source: org_study_id