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

Multiple Sclerosis Clinical Trial

— DOT-MS  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04260711
• Other study ID #: NL71260.029.19
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2020
• Est. completion date: January 1, 2024

Study information

• Verified date: October 2020
• Source: VU University Medical Center
• Contact: Eline Coerver, MSc
• Phone: +31204440717
• Email: e.coerver[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: January 1, 2024
• Est. primary completion date: August 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Multiple Sclerosis, Relapsing-Remitting
• Multiple Sclerosis, Secondary Progressive
• Sclerosis

Intervention

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

Locations

Country	Name	City	State
Netherlands	Amsterdam UMC	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
VU University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

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