Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS).

NCT ID: NCT04260711

Last Updated: 2020-10-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-01
• Study Completion Date: 2024-01-01

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.

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Secondary Progressive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Discontinuation of DMT

Discontinuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)

Group Type: EXPERIMENTAL

DMT

Intervention Type: DRUG

Discontinuation of patients' own disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)

Continuation of DMT

Continuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

DMT

Discontinuation of patients' own disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)

Intervention Type: DRUG

Other Intervention Names

Interferon; Glatiramer acetate; Dimethylfumarate; Teriflunomide

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amsterdam UMC, location VUmc

OTHER

Sponsor Role: lead

Responsible Party

Eline Coerver

Corresponding investigator, (also: E.M.M. Strijbis (coordinating investigator) and J. Killestein (principal investigator))

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

J. Killestein, prof. dr.

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC, location VUmc

Locations

Amsterdam UMC

Amsterdam, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Eline Coerver, MSc

Role: CONTACT

e.coerver@amsterdamumc.nl

+31204440717

Eva Strijbis, dr.

Role: CONTACT

e.strijbis@amsterdamumc.nl

Facility Contacts

Eline Coerver, MSc

Role: primary

e.coerver@amsterdamumc.nl

References

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.

Reference Type: DERIVED

PMID: 39652340 (View on PubMed)

Other Identifiers

NL71260.029.19

Identifier Type: -

Identifier Source: org_study_id