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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Ospedale Civico, Lugano
Sponsor:
Collaborator:
Ente Ospedaliero Cantonale, Ticino, Switzerland
Information provided by (Responsible Party):
Claudio Gobbi, Ospedale Civico, Lugano
ClinicalTrials.gov Identifier:
NCT01411514
First received: May 26, 2011
Last updated: October 25, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Drug: Prednisone
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Ospedale Civico, Lugano:

Primary Outcome Measures:
  • Expanded Disability Status Scale (EDSS) [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Expanded Disability Status Scale (EDSS) [ Time Frame: baseline, 25 days (end of treatment) ] [ Designated as safety issue: No ]
    the scores of the Expanded Disability Status Scale (EDSS) will be assessed at baseline, at end of treatment, 6, and 9 months after baseline;

  • Multiple Sclerosis Functional Composite Score (MSFC) [ Time Frame: baseline, 25 days (end of treatment) ] [ Designated as safety issue: No ]
    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)

  • Gd-enhancing lesions on T1-weighted images [ Time Frame: baseline, 25 days (end of treatment) ] [ Designated as safety issue: No ]
    the evolution of the number of Gd-enhancing lesions on T1-weighted images will be assessed

  • number of new T2-hyperintense lesions [ Time Frame: baseline, 25 days (end of treatment) ] [ Designated as safety issue: No ]
    the evolution of the number of new T2-hyperintense lesions will be assessed

  • mental status (MUSIC) [ Time Frame: baseline, 25 days (end of treatment) ] [ Designated as safety issue: No ]
    investigator administered questionnaire

  • Euroqol-5D (EQ-5D [ Time Frame: baseline, 25 days (end of treatment) ] [ Designated as safety issue: No ]
    patient reported quality of life

  • Functional Assessment Multiple Sclerosis (FAMS) [ Time Frame: at baseline, 25 days (end of treatment) ] [ Designated as safety issue: No ]
    Patient reported outcome

  • Beck Depression Inventory Second edition (BDI-II) [ Time Frame: baseline, 25 days (end of treatment) ] [ Designated as safety issue: No ]
    Investigator administered questionnaire

  • Fatigue Scale for Motor and Cognitive functions (FSMC) [ Time Frame: baseline, 25 days (end of treatment) ] [ Designated as safety issue: No ]
    Investigator administered questionnaire

  • Expanded Disability Status Scale (EDSS) [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    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.

  • Expanded Disability Status Scale (EDSS) [ Time Frame: baseline, 9 months ] [ Designated as safety issue: No ]
    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.

  • Multiple Sclerosis Functional Composite Score (MSFC) [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    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)

  • Multiple Sclerosis Functional Composite Score (MSFC) [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    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)

  • Multiple Sclerosis Functional Composite Score (MSFC) [ Time Frame: baseline, 9 months ] [ Designated as safety issue: No ]
    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)

  • Gd-enhancing lesions on T1-weighted images [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    the evolution of the number of Gd-enhancing lesions on T1-weighted images will be assessed

  • Gd-enhancing lesions on T1-weighted images [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    the evolution of the number of Gd-enhancing lesions on T1-weighted images will be assessed

  • number of new T2-hyperintense lesions [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    the evolution of the number of new T2-hyperintense lesions will be assessed

  • number of new T2-hyperintense lesions [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    the evolution of the number of new T2-hyperintense lesions will be assessed

  • mental status (MUSIC) [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    investigator administered questionnaire

  • mental status (MUSIC) [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    investigator administered questionnaire

  • Euroqol-5D (EQ-5D [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    patient reported quality of life

  • Euroqol-5D (EQ-5D [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    patient reported quality of life

  • Functional Assessment Multiple Sclerosis (FAMS) [ Time Frame: at baseline, 3 months ] [ Designated as safety issue: No ]
    Patient reported outcome

  • Functional Assessment Multiple Sclerosis (FAMS) [ Time Frame: at baseline, 6 months ] [ Designated as safety issue: No ]
    Patient reported outcome

  • Beck Depression Inventory Second edition (BDI-II) [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    Investigator administered questionnaire

  • Beck Depression Inventory Second edition (BDI-II) [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    Investigator administered questionnaire

  • Fatigue Scale for Motor and Cognitive functions (FSMC) [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    Investigator administered questionnaire

  • Fatigue Scale for Motor and Cognitive functions (FSMC) [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    Investigator administered questionnaire


Estimated Enrollment: 40
Study Start Date: August 2011
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prednisone Drug: 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 Name: Prednison Axapharm
Placebo Comparator: Placebo Drug: Placebo
Placebo tablets. They will be administered during 25 days
Other Name: Placebo tablets

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01411514

Contacts
Contact: Claudio Gobbi, MD +41 91 811 6501 Claudio.Gobbi@eoc.ch
Contact: Chiara Zecca, MD +41 91 811 6501 Chiara.Zecca@eoc.ch

Locations
Switzerland
Osepdale Civico Recruiting
Lugano, Ticino, Switzerland, 6903
Contact: Claudio Gobbi, MD    +41 91 811 6501    Claudio.Gobbi@eoc.ch   
Contact: Chiara Zecca, MD    +41 91 811 6501    Chiara.Zecca@eoc.ch   
Sub-Investigator: Ursula Candrian, MD         
Sub-Investigator: Marta Garcia Calle, MD         
Sub-Investigator: Chiara Zecca, MD         
Sponsors and Collaborators
Claudio Gobbi
Ente Ospedaliero Cantonale, Ticino, Switzerland
Investigators
Principal Investigator: Claudio Gobbi, MD Neurocenter of Southern Switzerland
Study Director: Claudio Gobbi, MD Neurocenter of Southern Switzerland
  More Information

Additional Information:
Publications:
Responsible Party: Claudio Gobbi, Dr. med., Ospedale Civico, Lugano
ClinicalTrials.gov Identifier: NCT01411514     History of Changes
Other Study ID Numbers: EOC.NC.10.04
Study First Received: May 26, 2011
Last Updated: October 25, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by Ospedale Civico, Lugano:
Relapsing remittent multipse sclerosis
Secondary progressive multiple sclerosis
Clinically isolated syndrome
Primary progressive multiple sclerosis

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Prednisone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 18, 2014