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

Not Applicable

• Conditions: Multiple Sclerosis; Multiple Sclerosis, Secondary Progressive; Multiple Sclerosis, Relapsing-Remitting
• Interventions: Drug: DMT

• Registration Number: NCT04260711
• Lead Sponsor: Amsterdam UMC, location VUmc

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-01-21
• Study First Submitted QC: 2020-02-05
• Study First Posted: 2020-02-07
• Study Start: 2020-07-01
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-13
• Last Update Posted: 2020-10-19
• Primary Completion: 2023-08-01
• Study Completion: 2024-01-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 130

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Clinical relapses	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	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).

Secondary Outcome Measures

Name	Time	Method
EDSS (Expanded Disability Status Scale)	2 years	This score indicates disability on a scale of 0 to 10. A higher score indicates more disability.
9-hole peg test	2 years	9-hole peg test (9HPT): test on hand function, measured in seconds. A shorter time indicates a better hand function.
Timed 25-Foot Walk	2 years	Timed 25-foot walk (T25FW): walking test, measured in seconds. A shorter time indicates a better walking function.
Symbol Digits Modalities Test	2 years	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	2 years	Number of lesions on T1 post-contrast MRI
MRI-parameter: T2 post-contrast lesion number	2 years	Number of lesions on T2-MRI
Multiple Sclerosis Impact Scale (MSIS-29)	2 years	Questionnaire on the impact of MS on day-to-day life
Short Form health survey (SF-36)	2 years	Questionnaire on general health
Checklist Individual Strength (CIS20r)	2 years	Questionnaire on fatigue
Treatment Satisfaction Questionnaire for Medication (TSQM)	2 years	Questionnaire on treatment satisfaction
EuroQol 5 dimensions questionnaire (EQ-5D-5L)	2 years	Questionnaire on quality of life and costs
Medical consumption questionnaire (iMCQ)	2 years	Questionnaire on medical consumption
Productivity costs questionnaire (iPCQ)	2 years	Questionnaire on productivity
Neurofilament light level in serum	2 years	Neurofilament light levels in serum

Trial Locations

Locations (1)

Amsterdam UMC; 🇳🇱 Amsterdam, Netherlands