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

October 13, 2020 updated by: Eline Coerver, Amsterdam UMC, location VUmc

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.

Study Overview

Study Type

Interventional

Enrollment (Anticipated)

130

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Discontinuation of DMT
Discontinuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)
Discontinuation of patients' own disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)
Other Names:
  • Glatiramer acetate
  • Interferon
  • Dimethylfumarate
  • Teriflunomide
NO_INTERVENTION: Continuation of DMT
Continuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
2 years
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).
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
EDSS (Expanded Disability Status Scale)
Time Frame: 2 years
This score indicates disability on a scale of 0 to 10. A higher score indicates more disability.
2 years
9-hole peg test
Time Frame: 2 years
9-hole peg test (9HPT): test on hand function, measured in seconds. A shorter time indicates a better hand function.
2 years
Timed 25-Foot Walk
Time Frame: 2 years
Timed 25-foot walk (T25FW): walking test, measured in seconds. A shorter time indicates a better walking function.
2 years
Symbol Digits Modalities Test
Time Frame: 2 years
Symbol Digits Modalities Test (SDMT): measures cognition. Scored with a number from 0 to 110, a higher score indicates better cognitive function.
2 years
MRI-parameter: T1 post-contrast lesion number
Time Frame: 2 years
Number of lesions on T1 post-contrast MRI
2 years
MRI-parameter: T2 post-contrast lesion number
Time Frame: 2 years
Number of lesions on T2-MRI
2 years
Multiple Sclerosis Impact Scale (MSIS-29)
Time Frame: 2 years
Questionnaire on the impact of MS on day-to-day life
2 years
Short Form health survey (SF-36)
Time Frame: 2 years
Questionnaire on general health
2 years
Checklist Individual Strength (CIS20r)
Time Frame: 2 years
Questionnaire on fatigue
2 years
Treatment Satisfaction Questionnaire for Medication (TSQM)
Time Frame: 2 years
Questionnaire on treatment satisfaction
2 years
EuroQol 5 dimensions questionnaire (EQ-5D-5L)
Time Frame: 2 years
Questionnaire on quality of life and costs
2 years
Medical consumption questionnaire (iMCQ)
Time Frame: 2 years
Questionnaire on medical consumption
2 years
Productivity costs questionnaire (iPCQ)
Time Frame: 2 years
Questionnaire on productivity
2 years
Neurofilament light level in serum
Time Frame: 2 years
Neurofilament light levels in serum
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: J. Killestein, prof. dr., Amsterdam UMC, location VUmc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 1, 2020

Primary Completion (ANTICIPATED)

August 1, 2023

Study Completion (ANTICIPATED)

January 1, 2024

Study Registration Dates

First Submitted

January 21, 2020

First Submitted That Met QC Criteria

February 5, 2020

First Posted (ACTUAL)

February 7, 2020

Study Record Updates

Last Update Posted (ACTUAL)

October 19, 2020

Last Update Submitted That Met QC Criteria

October 13, 2020

Last Verified

October 1, 2020

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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