Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS). (DOT-MS)
Primary Purpose
Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Secondary Progressive
Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
DMT
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis focused on measuring multiple sclerosis, disease modifying therapy
Eligibility Criteria
Inclusion Criteria:
- Minimum age of 18 years
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local privacy regulations.
- Definite diagnosis of relapsing-onset MS according to the revised McDonald 2017 criteria
- Treatment with one of the first-line DMTs: any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide
- Complete absence of inflammatory activity (no objectively defined and confirmed relapses, no significant number (2 or more) of new-T2 lesions and no contrast-enhancing lesions) for 5 consecutive years under first-line treatment
Exclusion Criteria:
- A switch between first-line disease modifying therapy over two years prior to inclusion, in case the switch has been due to in effectivity of the first DMT.
- Women who want to discontinue medication because of a pregnancy wish and women who are pregnant or expect to become pregnant during the study period
- Patients that have previously used interferon-beta and have been tested positive for neutralizing antibodies (NAbs).
Sites / Locations
- Amsterdam UMCRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Discontinuation of DMT
Continuation of DMT
Arm Description
Discontinuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)
Continuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)
Outcomes
Primary Outcome Measures
Clinical relapses
New clinically confirmed relapses (defined according to the definition most often used in MS phase-III trials: the onset of new or recurrent symptoms that last > 24 hours, that are accompanied by new objective abnormalities on a neurological examination and that are not explained by non-MS processes such as fever, infection, severe stress or drug toxicity).
New lesions on MRI-brain
New inflammatory disease activity on MRI (defined as 3 or more lesions on T2-weighted vimages or 2 or more gadolinium enhancing lesions on T1-weighted post-contrast MRI).
Secondary Outcome Measures
EDSS (Expanded Disability Status Scale)
This score indicates disability on a scale of 0 to 10. A higher score indicates more disability.
9-hole peg test
9-hole peg test (9HPT): test on hand function, measured in seconds. A shorter time indicates a better hand function.
Timed 25-Foot Walk
Timed 25-foot walk (T25FW): walking test, measured in seconds. A shorter time indicates a better walking function.
Symbol Digits Modalities Test
Symbol Digits Modalities Test (SDMT): measures cognition. Scored with a number from 0 to 110, a higher score indicates better cognitive function.
MRI-parameter: T1 post-contrast lesion number
Number of lesions on T1 post-contrast MRI
MRI-parameter: T2 post-contrast lesion number
Number of lesions on T2-MRI
Multiple Sclerosis Impact Scale (MSIS-29)
Questionnaire on the impact of MS on day-to-day life
Short Form health survey (SF-36)
Questionnaire on general health
Checklist Individual Strength (CIS20r)
Questionnaire on fatigue
Treatment Satisfaction Questionnaire for Medication (TSQM)
Questionnaire on treatment satisfaction
EuroQol 5 dimensions questionnaire (EQ-5D-5L)
Questionnaire on quality of life and costs
Medical consumption questionnaire (iMCQ)
Questionnaire on medical consumption
Productivity costs questionnaire (iPCQ)
Questionnaire on productivity
Neurofilament light level in serum
Neurofilament light levels in serum
Full Information
NCT ID
NCT04260711
First Posted
January 21, 2020
Last Updated
October 13, 2020
Sponsor
Amsterdam UMC, location VUmc
1. Study Identification
Unique Protocol Identification Number
NCT04260711
Brief Title
Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS).
Acronym
DOT-MS
Official Title
The Safety and Cost-effectiveness of Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS): a Randomized Rater-blinded Multicenter Trial.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2020 (Actual)
Primary Completion Date
August 1, 2023 (Anticipated)
Study Completion Date
January 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Amsterdam UMC, location VUmc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The aim of this study is to identify whether it is possible to safely discontinue treatment in relapsing-onset MS patients who have shown no evidence of active inflammation in the years prior to inclusion clinically and/or radiologically. The secondary objectives address the questions whether the discontinuation of first-line treatment has an effect on disability progression and whether the discontinuation of first-line treatment improves the quality of life for the patient. Furthermore, blood collections will be included to assess whether it is possible to retrospectively predict possible return of inflammatory activity with biomarkers such as neurofilament light (NFL) or patient characteristics such as disease activity prior to disease modifying therapy (DMT). In case of emerging disease activity after the cessation of therapy we will assess if reinitiation will lead to NEDA again, and if there are long-term consequences. If possible, post-hoc analysis are performed for the different types of treatment compounds.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Secondary Progressive
Keywords
multiple sclerosis, disease modifying therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
130 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Discontinuation of DMT
Arm Type
Experimental
Arm Description
Discontinuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)
Arm Title
Continuation of DMT
Arm Type
No Intervention
Arm Description
Continuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)
Intervention Type
Drug
Intervention Name(s)
DMT
Other Intervention Name(s)
Interferon, Glatiramer acetate, Dimethylfumarate, Teriflunomide
Intervention Description
Discontinuation of patients' own disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)
Primary Outcome Measure Information:
Title
Clinical relapses
Description
New clinically confirmed relapses (defined according to the definition most often used in MS phase-III trials: the onset of new or recurrent symptoms that last > 24 hours, that are accompanied by new objective abnormalities on a neurological examination and that are not explained by non-MS processes such as fever, infection, severe stress or drug toxicity).
Time Frame
2 years
Title
New lesions on MRI-brain
Description
New inflammatory disease activity on MRI (defined as 3 or more lesions on T2-weighted vimages or 2 or more gadolinium enhancing lesions on T1-weighted post-contrast MRI).
Time Frame
2 years
Secondary Outcome Measure Information:
Title
EDSS (Expanded Disability Status Scale)
Description
This score indicates disability on a scale of 0 to 10. A higher score indicates more disability.
Time Frame
2 years
Title
9-hole peg test
Description
9-hole peg test (9HPT): test on hand function, measured in seconds. A shorter time indicates a better hand function.
Time Frame
2 years
Title
Timed 25-Foot Walk
Description
Timed 25-foot walk (T25FW): walking test, measured in seconds. A shorter time indicates a better walking function.
Time Frame
2 years
Title
Symbol Digits Modalities Test
Description
Symbol Digits Modalities Test (SDMT): measures cognition. Scored with a number from 0 to 110, a higher score indicates better cognitive function.
Time Frame
2 years
Title
MRI-parameter: T1 post-contrast lesion number
Description
Number of lesions on T1 post-contrast MRI
Time Frame
2 years
Title
MRI-parameter: T2 post-contrast lesion number
Description
Number of lesions on T2-MRI
Time Frame
2 years
Title
Multiple Sclerosis Impact Scale (MSIS-29)
Description
Questionnaire on the impact of MS on day-to-day life
Time Frame
2 years
Title
Short Form health survey (SF-36)
Description
Questionnaire on general health
Time Frame
2 years
Title
Checklist Individual Strength (CIS20r)
Description
Questionnaire on fatigue
Time Frame
2 years
Title
Treatment Satisfaction Questionnaire for Medication (TSQM)
Description
Questionnaire on treatment satisfaction
Time Frame
2 years
Title
EuroQol 5 dimensions questionnaire (EQ-5D-5L)
Description
Questionnaire on quality of life and costs
Time Frame
2 years
Title
Medical consumption questionnaire (iMCQ)
Description
Questionnaire on medical consumption
Time Frame
2 years
Title
Productivity costs questionnaire (iPCQ)
Description
Questionnaire on productivity
Time Frame
2 years
Title
Neurofilament light level in serum
Description
Neurofilament light levels in serum
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Minimum age of 18 years
Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local privacy regulations.
Definite diagnosis of relapsing-onset MS according to the revised McDonald 2017 criteria
Treatment with one of the first-line DMTs: any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide
Complete absence of inflammatory activity (no objectively defined and confirmed relapses, no significant number (2 or more) of new-T2 lesions and no contrast-enhancing lesions) for 5 consecutive years under first-line treatment
Exclusion Criteria:
A switch between first-line disease modifying therapy over two years prior to inclusion, in case the switch has been due to in effectivity of the first DMT.
Women who want to discontinue medication because of a pregnancy wish and women who are pregnant or expect to become pregnant during the study period
Patients that have previously used interferon-beta and have been tested positive for neutralizing antibodies (NAbs).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eline Coerver, MSc
Phone
+31204440717
Email
e.coerver@amsterdamumc.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Eva Strijbis, dr.
Email
e.strijbis@amsterdamumc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J. Killestein, prof. dr.
Organizational Affiliation
Amsterdam UMC, location VUmc
Official's Role
Principal Investigator
Facility Information:
Facility Name
Amsterdam UMC
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eline Coerver, MSc
Email
e.coerver@amsterdamumc.nl
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS).
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