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Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS) (DISCOMS)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03073603
Recruitment Status : Completed
First Posted : March 8, 2017
Last Update Posted : December 20, 2021
Sponsor:
Collaborators:
Patient-Centered Outcomes Research Institute
National Multiple Sclerosis Society
University of Alabama at Birmingham
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
Natural history research in Multiple Sclerosis (MS) suggests that risk of relapses and new Magnetic Resonance Imaging (MRI) changes diminish significantly as people age, especially in MS patients 55 or older. Thus, the need to continue MS medicines that reduce relapses and new MRI lesions may also decrease as people age, especially in those who have not had relapses or MRI scan changes for prolonged times. This study plans to learn more about the safety of stopping MS medication in this population, as compared to continuing on the medication.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: Discontinuation of disease modifying therapy Drug: Standard of Care Phase 4

Detailed Description:

Participants will be randomized (1:1) to one of two groups. One group will stay on their current MS medication (Continue group), and one group will discontinue their medication (Discontinue group). They will also have some extra assessments done at their regular routine MS clinic appointment and every 6 months for the next 18-24 months. The following items will be done in addition to any assessments or procedures they are already having done as part of their clinical care:

  • Questionnaires about the participant's quality of life including questions about health, mood, thinking, and social life
  • Questionnaires about the participant's MS symptoms
  • Test of the participant's attention, concentration, and thinking
  • Test of the participant's physical symptoms
  • In addition to any MRIs the participants may get as part of their routine care, they will also have an MRI 6 months from their enrollment into the study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 259 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS)
Actual Study Start Date : April 20, 2017
Actual Primary Completion Date : August 31, 2021
Actual Study Completion Date : August 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Drug Continuation Arm
Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include ~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.
Drug: Standard of Care
Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include ~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.

Experimental: Drug Discontinuation Arm
Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include ~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.
Drug: Discontinuation of disease modifying therapy
Participants who will discontinue their current MS drug. No other changes to their treatment occur.




Primary Outcome Measures :
  1. Safety as measured by the proportion of participants developing a new MS relapse and/or MRI Brain Lesion over the course of the study duration. [ Time Frame: 18-24 months, based on time of enrollment ]
    The outcome is the proportion of participants in each group developing a new MS relapse and/or MRI brain lesion over the course of the study duration. Count of Participants with either a new MS relapse and/or a new brain MRI lesion is reported.


Secondary Outcome Measures :
  1. Proportion with Significant, Confirmed Change in Physical Disability using the Expanded Disability Status Scale (EDSS) [ Time Frame: Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment. ]
    The EDSS is a neurological examination performed by a blinded rater. This assessment is collected at each study visit. Increase in the EDSS score shows disease activity or progression, and must be observed six months later to be confirmed. Whether a confirmed change is significant depends on the subject's EDSS at baseline: for those with a baseline EDSS of 5.5 points or fewer, the increase must be at least one point to be significant; for those with a baseline EDSS of 6.0 points or greater, a change of at least 0.5 points is considered significant. We will calculate the percentage in each group of those who had a significant, confirmed change at anytime during the follow-up period.

  2. Change in Neuro-QoL (quality of life) short form scores. [ Time Frame: Baseline, 18-24 Months, based on time of enrollment ]
    The Neuro-QOL Adult PRO short form measures are collected to evaluate self-reported overall quality of life and functioning in patients with a variety of neurological conditions including MS. The Neuro-Qol short form scales consist of 5-9 single scale item scales. Raw scores are then converted to a standardized score with mean 50 and standard deviation 10. The Neuro-QoL short forms used in this study with higher scores representing better outcomes are: Upper Extremity Function, Lower Extremity Function, Cognitive -- General Concerns, Cognitive -- Executive Function, Communication, Positive Affect and Well-Being, Satisfaction with Social Roles and Activities, and Ability to Participate in Social Roles and Activities. The short forms used with lower scores representing better outcomes are: Fatigue, Sleep Disturbance, Anxiety, Depression, and Emotional-Behavioral Dyscontrol.

  3. Change in SymptoMScreen composite score (SymptoMScreen - overall symptom severity). [ Time Frame: Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment. ]
    SymptoMScreen will be collected to assess overall symptom severity. Participants self-report across multiple neurological domains (mobility, hand function, spasticity, pain, sensory, bladder, fatigue, vision, dizziness, cognition, depression, and anxiety). This scale is a single page, validated measure that allows for quick assessment of multiple symptoms. Single item scores are rated as 0-6 with higher numbers representing increased limitations and symptom severity. Composite score is calculated by summing the single item scores with total score ranges from 0 to 72.

  4. Change in Patient-Determined Disease Steps (PDDS - disability). [ Time Frame: Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment. ]
    Patient-Determined Disease Steps will be collected to assess changes in disability from the patient's perspective. This outcome measure is a single question. The scores range from 0 to 8, and a participant with a low score has less perceived disability than a participant with a higher score.

  5. Change in Symbol Digit Modalities Test (SDMT - cognition). [ Time Frame: Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment. ]
    The SDMT measures patient attention, concentration, and speed of information processing and has been validated for discriminating patients from controls. Possible scores range from 0 to 110, with higher scores indicating a better outcome.

  6. Evaluation of the patient's Quality of Life using the MSIS-29 Scale [ Time Frame: Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment. ]
    The Multiple Sclerosis Impact Scale (MSIS-29) will be collected to assess changes in quality of life from the patient's perspective. The MSIS has 29 questions. Each question asks the participant to rank how impacted they are in a certain aspect of their life. The options are 1 through 4. 1 indicates not at all impacted while 4 indicates extremely impacted. The lower the final score, the less impacted the participant is overall. Scores on the physical impact scale range from 20-80 and from 9-36 on the psychological impact scale. We will compare the proportion in each group who have had a change of 7.5 points or more (considered a clinically meaningful change).


Other Outcome Measures:
  1. Total Number of New T2 Lesions on MRI [ Time Frame: Baseline, then every 6 months for 2 years with one exception at 18 months. ]
    MRIs will be reviewed to determine the total number of new T2 lesions that develop for each subject over the course of the study. Lesion counts will be performed by the central MRI facility.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with either Relapsing-remitting MS (RRMS), Secondary progressive MS (SPMS), or Primary progressive MS (PPMS) by McDonald 2010 criteria.
  • Patients defined by subtype based on 2013 updated phenotypic criteria.
  • Progression of MS defined by the local PI either:

    • prospectively with an EDSS change of at least 1.0 points over the last two years, or
    • retrospectively, with any significant change in motor function over at least one year, unrelated to relapse.
  • 55 years of age or older at time of randomization;
  • No evidence of recent new inflammatory disease activity (inactive by the Lublin criteria16) with no new relapse for at least five years and no new MRI lesion for at least three years
  • Using any of the FDA-approved MS DMTs (to include:

    • interferon β-1a,
    • interferon β-1b,
    • glatiramer acetate,
    • natalizumab,
    • fingolimod,
    • dimethyl fumarate,
    • ocrelizumab, or
    • teriflunomide; continuously for no less than 5 years.
  • Taking most recent DMT continuously* for no less than two years.
  • Willing to be randomized per this protocol; each patient will be questioned as to their willingness to stay in the trial regardless of the group to which group they are randomized.
  • Willing to follow the protocol
  • Able to undergo a brain MRI without anesthesia

    • Continuously will be defined as no less than 75% of all prescribed doses, with no time of greater than four weeks from last intended dose to have missed a dose (8 weeks for natalizumab, i.e. one missed dose).

Exclusion Criteria:

  • Any MS relapse in the last five years, as determined at the screen visit by the PI
  • Any new or definitely enlarging T2/FLAIR lesion or new gadolinium-enhancing lesion within the past three years (at least two scans separated by at least three years must be reviewed) on brain or spine MRI scan. Lesions must be 3mm or larger to be exclusionary.
  • Significant (as defined by the PI) intolerance of presently-used DMT
  • More than two courses of acute, systemic (IV or oral) steroids in the last 5 years or any use within the last year. Course is defined as three or more days continuously, and not to exceed 14 days. No use of chronic, systemic steroids, defined as 15 or more days, in the last 5 years. Any use of steroids to treat MS relapse, possible relapse, or pseudo-relapse in the last 5 years.

    • Use of inhaled or topical steroids are not an exclusion criteria.
    • Use of oral steroids for no greater than 14 days given for a non-MS condition is not exclusionary.
  • Prior use of the following in the past 5 years:

    • alemtuzumab,
    • mitoxantrone,
    • cyclophosphamide,
    • methotrexate,
    • cyclosporine,
    • rituximab,
    • siponimod, or
    • cladribine
  • Prior use of any experimental agent used as a DMT for MS in the last five years
  • Other significant medical or psychiatric illness, if uncontrolled. Examples:

    • uncontrolled hypertension,
    • uncontrolled diabetes,
    • uncontrolled asthma, or
    • uncontrolled depression
  • Cancers other than basal cell skin cancers within the last 5 years
  • Unable to give informed consent or follow the protocol
  • Unable to undergo brain MRI
  • Unwilling to be randomized per this protocol
  • History of other chronic neurological illnesses that might mimic MS with chronic or intermittent symptoms (i.e. ALS, myasthenia gravis, chronic neuropathy, etc.)

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): NCT03073603


Locations
Show Show 19 study locations
Sponsors and Collaborators
University of Colorado, Denver
Patient-Centered Outcomes Research Institute
National Multiple Sclerosis Society
University of Alabama at Birmingham
Investigators
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Principal Investigator: John Corboy, MD University of Colorado, Denver
  Study Documents (Full-Text)

Documents provided by University of Colorado, Denver:
Informed Consent Form  [PDF] January 10, 2020

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT03073603    
Other Study ID Numbers: 15-2388
First Posted: March 8, 2017    Key Record Dates
Last Update Posted: December 20, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases