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

NCT04260711 | Unknown DMC

• 1 other identifier: NL71260.029.19
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

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

Keywords

multiple sclerosis; disease modifying therapy

Outcome Measures

Primary Outcomes (2)

• 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).

  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).

  2 years

Secondary Outcomes (14)

• EDSS (Expanded Disability Status Scale)

  2 years

• 9-hole peg test

  2 years

• Timed 25-Foot Walk

  2 years

• Symbol Digits Modalities Test

  2 years

• MRI-parameter: T1 post-contrast lesion number

  2 years

Study Arms (2)

Discontinuation of DMT

EXPERIMENTAL

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

Drug: DMT

Continuation of DMT

NO INTERVENTION

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

Interventions

DMT DRUG

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

Also known as: Interferon, Glatiramer acetate, Dimethylfumarate, Teriflunomide

Discontinuation of DMT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

Amsterdam UMC

Amsterdam, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 39652340 DERIVED

MeSH Terms

Conditions

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

Interventions

Interferons; Glatiramer Acetate; Dimethyl Fumarate; teriflunomide

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• J. Killestein, prof. dr.

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eline Coerver, MSc

CONTACT

+31204440717; e.coerver@amsterdamumc.nl

Eva Strijbis, dr.

CONTACT

e.strijbis@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Corresponding investigator, (also: E.M.M. Strijbis (coordinating investigator) and J. Killestein (principal investigator))

Study Record Dates

• First Submitted: January 21, 2020
• First Posted: February 7, 2020
• Study Start: July 1, 2020
• Primary Completion: August 1, 2023
• Study Completion: January 1, 2024
• Last Updated: October 19, 2020

Record last verified: 2020-10

Locations

NL (1)