- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04260711
Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS). (DOT-MS)
October 13, 2020 updated by: Eline Coerver, Amsterdam UMC, location VUmc
The Safety and Cost-effectiveness of Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS): a Randomized Rater-blinded Multicenter Trial.
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Anticipated)
130
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Eline Coerver, MSc
- Phone Number: +31204440717
- Email: e.coerver@amsterdamumc.nl
Study Contact Backup
- Name: Eva Strijbis, dr.
- Email: e.strijbis@amsterdamumc.nl
Study Locations
-
-
-
Amsterdam, Netherlands
- Recruiting
- Amsterdam UMC
-
Contact:
- Eline Coerver, MSc
- Email: e.coerver@amsterdamumc.nl
-
-
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 and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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).
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
- Masking: SINGLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Discontinuation of DMT
Discontinuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)
|
Discontinuation of patients' own disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)
Other Names:
|
NO_INTERVENTION: Continuation of DMT
Continuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical relapses
Time Frame: 2 years
|
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).
|
2 years
|
New lesions on MRI-brain
Time Frame: 2 years
|
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).
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
EDSS (Expanded Disability Status Scale)
Time Frame: 2 years
|
This score indicates disability on a scale of 0 to 10.
A higher score indicates more disability.
|
2 years
|
9-hole peg test
Time Frame: 2 years
|
9-hole peg test (9HPT): test on hand function, measured in seconds.
A shorter time indicates a better hand function.
|
2 years
|
Timed 25-Foot Walk
Time Frame: 2 years
|
Timed 25-foot walk (T25FW): walking test, measured in seconds.
A shorter time indicates a better walking function.
|
2 years
|
Symbol Digits Modalities Test
Time Frame: 2 years
|
Symbol Digits Modalities Test (SDMT): measures cognition.
Scored with a number from 0 to 110, a higher score indicates better cognitive function.
|
2 years
|
MRI-parameter: T1 post-contrast lesion number
Time Frame: 2 years
|
Number of lesions on T1 post-contrast MRI
|
2 years
|
MRI-parameter: T2 post-contrast lesion number
Time Frame: 2 years
|
Number of lesions on T2-MRI
|
2 years
|
Multiple Sclerosis Impact Scale (MSIS-29)
Time Frame: 2 years
|
Questionnaire on the impact of MS on day-to-day life
|
2 years
|
Short Form health survey (SF-36)
Time Frame: 2 years
|
Questionnaire on general health
|
2 years
|
Checklist Individual Strength (CIS20r)
Time Frame: 2 years
|
Questionnaire on fatigue
|
2 years
|
Treatment Satisfaction Questionnaire for Medication (TSQM)
Time Frame: 2 years
|
Questionnaire on treatment satisfaction
|
2 years
|
EuroQol 5 dimensions questionnaire (EQ-5D-5L)
Time Frame: 2 years
|
Questionnaire on quality of life and costs
|
2 years
|
Medical consumption questionnaire (iMCQ)
Time Frame: 2 years
|
Questionnaire on medical consumption
|
2 years
|
Productivity costs questionnaire (iPCQ)
Time Frame: 2 years
|
Questionnaire on productivity
|
2 years
|
Neurofilament light level in serum
Time Frame: 2 years
|
Neurofilament light levels in serum
|
2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: J. Killestein, prof. dr., Amsterdam UMC, location VUmc
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 (ACTUAL)
July 1, 2020
Primary Completion (ANTICIPATED)
August 1, 2023
Study Completion (ANTICIPATED)
January 1, 2024
Study Registration Dates
First Submitted
January 21, 2020
First Submitted That Met QC Criteria
February 5, 2020
First Posted (ACTUAL)
February 7, 2020
Study Record Updates
Last Update Posted (ACTUAL)
October 19, 2020
Last Update Submitted That Met QC Criteria
October 13, 2020
Last Verified
October 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Immune System Diseases
- Demyelinating Autoimmune Diseases, CNS
- Autoimmune Diseases of the Nervous System
- Demyelinating Diseases
- Autoimmune Diseases
- Multiple Sclerosis
- Multiple Sclerosis, Chronic Progressive
- Sclerosis
- Multiple Sclerosis, Relapsing-Remitting
- Physiological Effects of Drugs
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Adjuvants, Immunologic
- Interferons
- Glatiramer Acetate
- (T,G)-A-L
- Dimethyl Fumarate
- Teriflunomide
Other Study ID Numbers
- NL71260.029.19
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
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.
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