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

December 17, 2015 updated by: Claudio Gobbi

Phase IV Study of Oral Prednisone Taper vs. Placebo Following Intravenous Steroids for the Treatment of Acute Relapses in Multiple Sclerosis Within the Ticino Cohort

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Ticino
      • Lugano, Ticino, Switzerland, 6903
        • Osepdale Civico

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo tablets. They will be administered during 25 days
Other Names:
  • Placebo tablets
Experimental: 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
Other Names:
  • Prednison Axapharm

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Expanded Disability Status Scale (EDSS)
Time Frame: baseline, 3 months
The scores of the Expanded Disability Status Scale (EDSS) will be assessed at baseline, defined as start of oral treatment with prednisone or placebo (Day 1), and 3 months after baseline.
baseline, 3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Expanded Disability Status Scale (EDSS)
Time Frame: baseline, 25 days (end of treatment)
the scores of the Expanded Disability Status Scale (EDSS) will be assessed at baseline, at end of treatment, 6, and 9 months after baseline;
baseline, 25 days (end of treatment)
Multiple Sclerosis Functional Composite Score (MSFC)
Time Frame: baseline, 25 days (end of treatment)
the Multiple Sclerosis Functional Composite Score (MSFC) includes the Timed 25 foot-walk-test, the 9 Hole Peg test and Paced Auditorial Addition Test (PASAT)
baseline, 25 days (end of treatment)
Gd-enhancing lesions on T1-weighted images
Time Frame: baseline, 25 days (end of treatment)
the evolution of the number of Gd-enhancing lesions on T1-weighted images will be assessed
baseline, 25 days (end of treatment)
number of new T2-hyperintense lesions
Time Frame: baseline, 25 days (end of treatment)
the evolution of the number of new T2-hyperintense lesions will be assessed
baseline, 25 days (end of treatment)
mental status (MUSIC)
Time Frame: baseline, 25 days (end of treatment)
investigator administered questionnaire
baseline, 25 days (end of treatment)
Euroqol-5D (EQ-5D
Time Frame: baseline, 25 days (end of treatment)
patient reported quality of life
baseline, 25 days (end of treatment)
Functional Assessment Multiple Sclerosis (FAMS)
Time Frame: at baseline, 25 days (end of treatment)
Patient reported outcome
at baseline, 25 days (end of treatment)
Beck Depression Inventory Second edition (BDI-II)
Time Frame: baseline, 25 days (end of treatment)
Investigator administered questionnaire
baseline, 25 days (end of treatment)
Fatigue Scale for Motor and Cognitive functions (FSMC)
Time Frame: baseline, 25 days (end of treatment)
Investigator administered questionnaire
baseline, 25 days (end of treatment)
Expanded Disability Status Scale (EDSS)
Time Frame: baseline, 6 months
The scores of the Expanded Disability Status Scale (EDSS) will be assessed at baseline, defined as start of oral treatment with prednisone or placebo (Day 1), and 6 months after baseline.
baseline, 6 months
Expanded Disability Status Scale (EDSS)
Time Frame: baseline, 9 months
The scores of the Expanded Disability Status Scale (EDSS) will be assessed at baseline, defined as start of oral treatment with prednisone or placebo (Day 1), and 9 months after baseline.
baseline, 9 months
Multiple Sclerosis Functional Composite Score (MSFC)
Time Frame: baseline, 3 months
the Multiple Sclerosis Functional Composite Score (MSFC) includes the Timed 25 foot-walk-test, the 9 Hole Peg test and Paced Auditorial Addition Test (PASAT)
baseline, 3 months
Multiple Sclerosis Functional Composite Score (MSFC)
Time Frame: baseline, 6 months
the Multiple Sclerosis Functional Composite Score (MSFC) includes the Timed 25 foot-walk-test, the 9 Hole Peg test and Paced Auditorial Addition Test (PASAT)
baseline, 6 months
Multiple Sclerosis Functional Composite Score (MSFC)
Time Frame: baseline, 9 months
the Multiple Sclerosis Functional Composite Score (MSFC) includes the Timed 25 foot-walk-test, the 9 Hole Peg test and Paced Auditorial Addition Test (PASAT)
baseline, 9 months
Gd-enhancing lesions on T1-weighted images
Time Frame: baseline, 3 months
the evolution of the number of Gd-enhancing lesions on T1-weighted images will be assessed
baseline, 3 months
Gd-enhancing lesions on T1-weighted images
Time Frame: baseline, 6 months
the evolution of the number of Gd-enhancing lesions on T1-weighted images will be assessed
baseline, 6 months
number of new T2-hyperintense lesions
Time Frame: baseline, 3 months
the evolution of the number of new T2-hyperintense lesions will be assessed
baseline, 3 months
number of new T2-hyperintense lesions
Time Frame: baseline, 6 months
the evolution of the number of new T2-hyperintense lesions will be assessed
baseline, 6 months
mental status (MUSIC)
Time Frame: baseline, 3 months
investigator administered questionnaire
baseline, 3 months
mental status (MUSIC)
Time Frame: baseline, 6 months
investigator administered questionnaire
baseline, 6 months
Euroqol-5D (EQ-5D
Time Frame: baseline, 3 months
patient reported quality of life
baseline, 3 months
Euroqol-5D (EQ-5D
Time Frame: baseline, 6 months
patient reported quality of life
baseline, 6 months
Functional Assessment Multiple Sclerosis (FAMS)
Time Frame: at baseline, 3 months
Patient reported outcome
at baseline, 3 months
Functional Assessment Multiple Sclerosis (FAMS)
Time Frame: at baseline, 6 months
Patient reported outcome
at baseline, 6 months
Beck Depression Inventory Second edition (BDI-II)
Time Frame: baseline, 3 months
Investigator administered questionnaire
baseline, 3 months
Beck Depression Inventory Second edition (BDI-II)
Time Frame: baseline, 6 months
Investigator administered questionnaire
baseline, 6 months
Fatigue Scale for Motor and Cognitive functions (FSMC)
Time Frame: baseline, 3 months
Investigator administered questionnaire
baseline, 3 months
Fatigue Scale for Motor and Cognitive functions (FSMC)
Time Frame: baseline, 6 months
Investigator administered questionnaire
baseline, 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Claudio Gobbi, MD, Neurocenter of Southern Switzerland
  • Study Director: Claudio Gobbi, MD, Neurocenter of Southern Switzerland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2011

Primary Completion (Actual)

January 1, 2015

Study Completion (Actual)

January 1, 2015

Study Registration Dates

First Submitted

May 26, 2011

First Submitted That Met QC Criteria

August 5, 2011

First Posted (Estimate)

August 8, 2011

Study Record Updates

Last Update Posted (Estimate)

December 18, 2015

Last Update Submitted That Met QC Criteria

December 17, 2015

Last Verified

December 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Multiple Sclerosis

Clinical Trials on Prednisone

3
Subscribe