Multiple SclerosisDOT-MSNCT04260711
Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS).
A study testing DMT in people with Multiple Sclerosis and Multiple Sclerosis, Relapsing-Remitting, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Secondary Progressive
- What is being tested?
- DMT
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Jul 2020to 1 Jan 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
Eva Strijbis, dr. contact
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam UMC
Amsterdam
Eline Coerver, MSc, e.coerver@amsterdamumc.nl
About this study
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.
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.
- Conditions
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Secondary Progressive
- Being tested
- DMT
- Keywords
- multiple sclerosis, disease modifying therapy
- Medical subject headings
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Chronic Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DMTDrug
Also called Interferon, Glatiramer acetate, Dimethylfumarate, Teriflunomide
Discontinuation of patients' own disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)
| Study group | Role | What they receive |
|---|---|---|
| Discontinuation of DMT | Experimental | Discontinuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide) Receives: Drug: DMT |
| Continuation of DMT | No intervention | Continuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 2 years
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).
Measured: 2 years
Secondary outcomes (14)
EDSS (Expanded Disability Status Scale)
This score indicates disability on a scale of 0 to 10. A higher score indicates more disability.
Measured: 2 years
9-hole peg test
9-hole peg test (9HPT): test on hand function, measured in seconds. A shorter time indicates a better hand function.
Measured: 2 years
Timed 25-Foot Walk
Timed 25-foot walk (T25FW): walking test, measured in seconds. A shorter time indicates a better walking function.
Measured: 2 years
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.
Measured: 2 years
MRI-parameter: T1 post-contrast lesion number
Number of lesions on T1 post-contrast MRI
Measured: 2 years
MRI-parameter: T2 post-contrast lesion number
Number of lesions on T2-MRI
Measured: 2 years
Multiple Sclerosis Impact Scale (MSIS-29)
Questionnaire on the impact of MS on day-to-day life
Measured: 2 years
Short Form health survey (SF-36)
Questionnaire on general health
Measured: 2 years
Checklist Individual Strength (CIS20r)
Questionnaire on fatigue
Measured: 2 years
Treatment Satisfaction Questionnaire for Medication (TSQM)
Questionnaire on treatment satisfaction
Measured: 2 years
EuroQol 5 dimensions questionnaire (EQ-5D-5L)
Questionnaire on quality of life and costs
Measured: 2 years
Medical consumption questionnaire (iMCQ)
Questionnaire on medical consumption
Measured: 2 years
Productivity costs questionnaire (iPCQ)
Questionnaire on productivity
Measured: 2 years
Neurofilament light level in serum
Neurofilament light levels in serum
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2020
- Study start1 Jul 2020
- Primary completion1 Aug 2023 (estimated)
- Study completion1 Jan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eline Coerver, Amsterdam UMC, location VUmc
- Investigators
- J. Killestein, prof. dr., Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04260711
- Sponsor's protocol ID
- NL71260.029.19
- Acronym
- DOT-MS
- Status last verified
- Oct 2020
- First submitted
- 21 Jan 2020
- Last updated
- 19 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Coerver EME, Fung WH, de Beukelaar J, Bouvy WH, Canta LR, Gerlach OHH, Hoitsma E, Hoogervorst ELJ, de Jong BA, Kalkers NF, van Kempen ZLE, Lovenich H, van Munster CEP, van Oosten BW, Smolders J, Vennegoor A, Zeinstra EMPE, Barrantes-Cepas M, Kooij G, Schoonheim MM, Lissenberg-Witte BI, Teunissen CE, Moraal B, Barkhof F, Uitdehaag BMJ, Mostert J, Killestein J, Strijbis EMM. Discontinuation of First-Line Disease-Modifying Therapy in Patients With Stable Multiple Sclerosis: The DOT-MS Randomized Clinical Trial. JAMA Neurol. 2025 Feb 1;82(2):123-131. doi: 10.1001/jamaneurol.2024.4164.
PubMed 39652340
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04260711
- Acronym / sponsor ID
- DOT-MS / NL71260.029.19
- Conditions
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Secondary Progressive
- Keywords
- multiple sclerosis, disease modifying therapy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- 1 Aug 2023 (estimated)
- Study completion
- 1 Jan 2024 (estimated)
- First posted
- 7 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Discontinuation of DMT | Experimental | Drug: DMTDiscontinuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide) |
| Continuation of DMT | No intervention | –Continuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (3 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DMTAlso: Interferon, Glatiramer acetate, Dimethylfumarate, TeriflunomideDiscontinuation of patients' own disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide) | Drug | Discontinuation of DMT |
Primary outcome
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).
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).
14 secondary outcomes
EDSS (Expanded Disability Status Scale)
Time frame: 2 years
9-hole peg test
Time frame: 2 years
Timed 25-Foot Walk
Time frame: 2 years
Symbol Digits Modalities Test
Time frame: 2 years
MRI-parameter: T1 post-contrast lesion number
Time frame: 2 years
MRI-parameter: T2 post-contrast lesion number
Time frame: 2 years
Multiple Sclerosis Impact Scale (MSIS-29)
Time frame: 2 years
Short Form health survey (SF-36)
Time frame: 2 years
Checklist Individual Strength (CIS20r)
Time frame: 2 years
Treatment Satisfaction Questionnaire for Medication (TSQM)
Time frame: 2 years
EuroQol 5 dimensions questionnaire (EQ-5D-5L)
Time frame: 2 years
Medical consumption questionnaire (iMCQ)
Time frame: 2 years
Productivity costs questionnaire (iPCQ)
Time frame: 2 years
Neurofilament light level in serum
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2020.
- Derived from this study: PubMed 39652340Coerver EME, Fung WH, de Beukelaar J, Bouvy WH, Canta LR, Gerlach OHH, Hoitsma E, Hoogervorst ELJ, de Jong BA, Kalkers NF, van Kempen ZLE, Lovenich H, van Munster CEP, van Oosten BW, Smolders J, Vennegoor A, Zeinstra EMPE, Barrantes-Cepas M, Kooij G, Schoonheim MM, Lissenberg-Witte BI, Teunissen CE, Moraal B, Barkhof F, Uitdehaag BMJ, Mostert J, Killestein J, Strijbis EMM. Discontinuation of First-Line Disease-Modifying Therapy in Patients With Stable Multiple Sclerosis: The DOT-MS Randomized Clinical Trial. JAMA Neurol. 2025 Feb 1;82(2):123-131. doi: 10.1001/jamaneurol.2024.4164.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eva Strijbis, dr. contact
J. Killestein, prof. dr. principal investigator
Amsterdam UMC, location VUmc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing DMT in people with Multiple Sclerosis and Multiple Sclerosis, Relapsing-Remitting, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eline Coerver, MSc (+31204440717, e.coerver@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical relapses (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04260711, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2020.