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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04260711
Recruitment Status : Recruiting
First Posted : February 7, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
Eline Coerver, VU University Medical Center

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.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Multiple Sclerosis, Secondary Progressive Drug: DMT Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
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.
Actual Study Start Date : July 1, 2020
Estimated Primary Completion Date : August 1, 2023
Estimated Study Completion Date : January 1, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Discontinuation of DMT
Discontinuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)
Drug: DMT
Discontinuation of patients' own disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)
Other Names:
  • Interferon
  • Glatiramer acetate
  • Dimethylfumarate
  • Teriflunomide

No Intervention: Continuation of DMT
Continuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)



Primary Outcome Measures :
  1. 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. 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).


Secondary Outcome Measures :
  1. 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. 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.

  3. 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.

  4. 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.

  5. MRI-parameter: T1 post-contrast lesion number [ Time Frame: 2 years ]
    Number of lesions on T1 post-contrast MRI

  6. MRI-parameter: T2 post-contrast lesion number [ Time Frame: 2 years ]
    Number of lesions on T2-MRI

  7. Multiple Sclerosis Impact Scale (MSIS-29) [ Time Frame: 2 years ]
    Questionnaire on the impact of MS on day-to-day life

  8. Short Form health survey (SF-36) [ Time Frame: 2 years ]
    Questionnaire on general health

  9. Checklist Individual Strength (CIS20r) [ Time Frame: 2 years ]
    Questionnaire on fatigue

  10. Treatment Satisfaction Questionnaire for Medication (TSQM) [ Time Frame: 2 years ]
    Questionnaire on treatment satisfaction

  11. EuroQol 5 dimensions questionnaire (EQ-5D-5L) [ Time Frame: 2 years ]
    Questionnaire on quality of life and costs

  12. Medical consumption questionnaire (iMCQ) [ Time Frame: 2 years ]
    Questionnaire on medical consumption

  13. Productivity costs questionnaire (iPCQ) [ Time Frame: 2 years ]
    Questionnaire on productivity

  14. Neurofilament light level in serum [ Time Frame: 2 years ]
    Neurofilament light levels in serum



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04260711


Contacts
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Contact: Eline Coerver, MSc +31204440717 e.coerver@amsterdamumc.nl
Contact: Eva Strijbis, dr. e.strijbis@amsterdamumc.nl

Locations
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Netherlands
Amsterdam UMC Recruiting
Amsterdam, Netherlands
Contact: Eline Coerver, MSc       e.coerver@amsterdamumc.nl   
Sponsors and Collaborators
VU University Medical Center
Investigators
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Principal Investigator: J. Killestein, prof. dr. Amsterdam UMC, location VUmc
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Responsible Party: Eline Coerver, Corresponding investigator, (also: E.M.M. Strijbis (coordinating investigator) and J. Killestein (principal investigator)), VU University Medical Center
ClinicalTrials.gov Identifier: NCT04260711    
Other Study ID Numbers: NL71260.029.19
First Posted: February 7, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eline Coerver, VU University Medical Center:
multiple sclerosis
disease modifying therapy
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Multiple Sclerosis, Chronic Progressive
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Interferons
Glatiramer Acetate
Dimethyl Fumarate
(T,G)-A-L
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Antirheumatic Agents
Dermatologic Agents