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

Primary Purpose

Multiple Sclerosis

Status
Terminated
Phase
Phase 4
Locations
Switzerland
Study Type
Interventional
Intervention
Prednisone
Placebo
Sponsored by
Claudio Gobbi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring Relapsing remittent multipse sclerosis, Secondary progressive multiple sclerosis, Clinically isolated syndrome, Primary progressive multiple sclerosis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Osepdale Civico

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Prednisone

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Expanded Disability Status Scale (EDSS)
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)
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)
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
the evolution of the number of Gd-enhancing lesions on T1-weighted images will be assessed
number of new T2-hyperintense lesions
the evolution of the number of new T2-hyperintense lesions will be assessed
mental status (MUSIC)
investigator administered questionnaire
Euroqol-5D (EQ-5D
patient reported quality of life
Functional Assessment Multiple Sclerosis (FAMS)
Patient reported outcome
Beck Depression Inventory Second edition (BDI-II)
Investigator administered questionnaire
Fatigue Scale for Motor and Cognitive functions (FSMC)
Investigator administered questionnaire
Expanded Disability Status Scale (EDSS)
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)
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)
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)
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)
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
the evolution of the number of Gd-enhancing lesions on T1-weighted images will be assessed
Gd-enhancing lesions on T1-weighted images
the evolution of the number of Gd-enhancing lesions on T1-weighted images will be assessed
number of new T2-hyperintense lesions
the evolution of the number of new T2-hyperintense lesions will be assessed
number of new T2-hyperintense lesions
the evolution of the number of new T2-hyperintense lesions will be assessed
mental status (MUSIC)
investigator administered questionnaire
mental status (MUSIC)
investigator administered questionnaire
Euroqol-5D (EQ-5D
patient reported quality of life
Euroqol-5D (EQ-5D
patient reported quality of life
Functional Assessment Multiple Sclerosis (FAMS)
Patient reported outcome
Functional Assessment Multiple Sclerosis (FAMS)
Patient reported outcome
Beck Depression Inventory Second edition (BDI-II)
Investigator administered questionnaire
Beck Depression Inventory Second edition (BDI-II)
Investigator administered questionnaire
Fatigue Scale for Motor and Cognitive functions (FSMC)
Investigator administered questionnaire
Fatigue Scale for Motor and Cognitive functions (FSMC)
Investigator administered questionnaire

Full Information

First Posted
May 26, 2011
Last Updated
December 17, 2015
Sponsor
Claudio Gobbi
Collaborators
Ente Ospedaliero Cantonale, Ticino, Switzerland
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1. Study Identification

Unique Protocol Identification Number
NCT01411514
Brief Title
Oral Prednisone Taper Versus Placebo for the Treatment of Acute Relapses in Multiple Sclerosis
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Terminated
Why Stopped
Difficulties to recruit patients
Study Start Date
August 2011 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Claudio Gobbi
Collaborators
Ente Ospedaliero Cantonale, Ticino, Switzerland

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Relapsing remittent multipse sclerosis, Secondary progressive multiple sclerosis, Clinically isolated syndrome, Primary progressive multiple sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Prednisone
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Prednisone
Other Intervention Name(s)
Prednison Axapharm
Intervention Description
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
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo tablets
Intervention Description
Placebo tablets. They will be administered during 25 days
Primary Outcome Measure Information:
Title
Expanded Disability Status Scale (EDSS)
Description
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.
Time Frame
baseline, 3 months
Secondary Outcome Measure Information:
Title
Expanded Disability Status Scale (EDSS)
Description
the scores of the Expanded Disability Status Scale (EDSS) will be assessed at baseline, at end of treatment, 6, and 9 months after baseline;
Time Frame
baseline, 25 days (end of treatment)
Title
Multiple Sclerosis Functional Composite Score (MSFC)
Description
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)
Time Frame
baseline, 25 days (end of treatment)
Title
Gd-enhancing lesions on T1-weighted images
Description
the evolution of the number of Gd-enhancing lesions on T1-weighted images will be assessed
Time Frame
baseline, 25 days (end of treatment)
Title
number of new T2-hyperintense lesions
Description
the evolution of the number of new T2-hyperintense lesions will be assessed
Time Frame
baseline, 25 days (end of treatment)
Title
mental status (MUSIC)
Description
investigator administered questionnaire
Time Frame
baseline, 25 days (end of treatment)
Title
Euroqol-5D (EQ-5D
Description
patient reported quality of life
Time Frame
baseline, 25 days (end of treatment)
Title
Functional Assessment Multiple Sclerosis (FAMS)
Description
Patient reported outcome
Time Frame
at baseline, 25 days (end of treatment)
Title
Beck Depression Inventory Second edition (BDI-II)
Description
Investigator administered questionnaire
Time Frame
baseline, 25 days (end of treatment)
Title
Fatigue Scale for Motor and Cognitive functions (FSMC)
Description
Investigator administered questionnaire
Time Frame
baseline, 25 days (end of treatment)
Title
Expanded Disability Status Scale (EDSS)
Description
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.
Time Frame
baseline, 6 months
Title
Expanded Disability Status Scale (EDSS)
Description
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.
Time Frame
baseline, 9 months
Title
Multiple Sclerosis Functional Composite Score (MSFC)
Description
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)
Time Frame
baseline, 3 months
Title
Multiple Sclerosis Functional Composite Score (MSFC)
Description
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)
Time Frame
baseline, 6 months
Title
Multiple Sclerosis Functional Composite Score (MSFC)
Description
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)
Time Frame
baseline, 9 months
Title
Gd-enhancing lesions on T1-weighted images
Description
the evolution of the number of Gd-enhancing lesions on T1-weighted images will be assessed
Time Frame
baseline, 3 months
Title
Gd-enhancing lesions on T1-weighted images
Description
the evolution of the number of Gd-enhancing lesions on T1-weighted images will be assessed
Time Frame
baseline, 6 months
Title
number of new T2-hyperintense lesions
Description
the evolution of the number of new T2-hyperintense lesions will be assessed
Time Frame
baseline, 3 months
Title
number of new T2-hyperintense lesions
Description
the evolution of the number of new T2-hyperintense lesions will be assessed
Time Frame
baseline, 6 months
Title
mental status (MUSIC)
Description
investigator administered questionnaire
Time Frame
baseline, 3 months
Title
mental status (MUSIC)
Description
investigator administered questionnaire
Time Frame
baseline, 6 months
Title
Euroqol-5D (EQ-5D
Description
patient reported quality of life
Time Frame
baseline, 3 months
Title
Euroqol-5D (EQ-5D
Description
patient reported quality of life
Time Frame
baseline, 6 months
Title
Functional Assessment Multiple Sclerosis (FAMS)
Description
Patient reported outcome
Time Frame
at baseline, 3 months
Title
Functional Assessment Multiple Sclerosis (FAMS)
Description
Patient reported outcome
Time Frame
at baseline, 6 months
Title
Beck Depression Inventory Second edition (BDI-II)
Description
Investigator administered questionnaire
Time Frame
baseline, 3 months
Title
Beck Depression Inventory Second edition (BDI-II)
Description
Investigator administered questionnaire
Time Frame
baseline, 6 months
Title
Fatigue Scale for Motor and Cognitive functions (FSMC)
Description
Investigator administered questionnaire
Time Frame
baseline, 3 months
Title
Fatigue Scale for Motor and Cognitive functions (FSMC)
Description
Investigator administered questionnaire
Time Frame
baseline, 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claudio Gobbi, MD
Organizational Affiliation
Neurocenter of Southern Switzerland
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Claudio Gobbi, MD
Organizational Affiliation
Neurocenter of Southern Switzerland
Official's Role
Study Director
Facility Information:
Facility Name
Osepdale Civico
City
Lugano
State/Province
Ticino
ZIP/Postal Code
6903
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
16324087
Citation
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.
Results Reference
background
PubMed Identifier
19588409
Citation
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.
Results Reference
background
PubMed Identifier
19949030
Citation
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.
Results Reference
background
PubMed Identifier
18459972
Citation
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.
Results Reference
background
Links:
URL
http://www.eoc.ch/
Description
Related information to the institution
URL
http://www.multiplesklerose.ch/
Description
Non profit organisazion that supports multiple sclerosis patients

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

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