Back to resultsDiscontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS) (DISCOMS)
Primary Purpose
Multiple Sclerosis
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Discontinuation of disease modifying therapy
Standard of Care
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis
Eligibility 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.)
Sites / Locations
- University of Southern California
- University of Colorado Denver - Anschutz Medical Campus
- Georgetown University
- University of Miami
- University of Kansas Medical Center
- Massachusetts General Hospital
- Washington University St. Louis
- NYU Langone Medical Center
- Mt. Sinai University
- University of Rochester
- Cleveland Clinic
- The Ohio State University
- Oregon Health and Science University
- University of Pennsylvania
- Thomas Jefferson University
- University of Pittsburgh
- Vanderbilt University
- University of Virginia
- Swedish Health Services
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Drug Continuation Arm
Drug Discontinuation Arm
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Number of Participants Developing a New MS Relapse and/or MRI Brain Lesion Over the Course of the Study Duration
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
Number With Disability Progression Confirmed at 6 Months Using the Expanded Disability Status Scale (EDSS)
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 change at anytime during the follow-up period, which was then confirmed at 6 months later.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Upper Extremity Function
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.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Lower Extremity Function
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.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Fatigue
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.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Sleep Disturbance
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.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- General Concerns
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.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Executive Function
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.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Communication
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.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Anxiety
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.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Depression
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.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Positive Affect and Well-Being
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.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Emotional-Behavioral Dyscontrol
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.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Satisfaction With Social Roles and Activities
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.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Ability to Participate in Social Roles and Activities
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.
Change in SymptoMScreen Composite Score (SymptoMScreen - Overall Symptom Severity).
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.
Change in Patient-Determined Disease Steps (PDDS - Disability).
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.
Change in Symbol Digit Modalities Test (SDMT - Cognition).
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.
Evaluation of the Patient's Quality of Life Using the MSIS-29 Scale -- Physical Impact
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).
Evaluation of the Patient's Quality of Life Using the MSIS-29 Scale -- Psychological Impact
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).
Full Information
NCT ID
NCT03073603
First Posted
January 18, 2017
Last Updated
August 14, 2023
Sponsor
University of Colorado, Denver
Collaborators
Patient-Centered Outcomes Research Institute, National Multiple Sclerosis Society, University of Alabama at Birmingham
1. Study Identification
Unique Protocol Identification Number
NCT03073603
Brief Title
Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS)
Acronym
DISCOMS
Official Title
Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
April 20, 2017 (Actual)
Primary Completion Date
August 31, 2021 (Actual)
Study Completion Date
August 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
Patient-Centered Outcomes Research Institute, National Multiple Sclerosis Society, University of Alabama at Birmingham
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
259 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Drug Continuation Arm
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Drug Discontinuation Arm
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Discontinuation of disease modifying therapy
Intervention Description
Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Intervention Type
Drug
Intervention Name(s)
Standard of Care
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants Developing a New MS Relapse and/or MRI Brain Lesion Over the Course of the Study Duration
Description
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.
Time Frame
18-24 months, based on time of enrollment
Secondary Outcome Measure Information:
Title
Number With Disability Progression Confirmed at 6 Months Using the Expanded Disability Status Scale (EDSS)
Description
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 change at anytime during the follow-up period, which was then confirmed at 6 months later.
Time Frame
Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment.
Title
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Upper Extremity Function
Description
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.
Time Frame
Baseline, 18-24 Months, based on time of enrollment
Title
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Lower Extremity Function
Description
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.
Time Frame
Baseline, 18-24 Months, based on time of enrollment
Title
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Fatigue
Description
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.
Time Frame
Baseline, 18-24 Months, based on time of enrollment
Title
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Sleep Disturbance
Description
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.
Time Frame
Baseline, 18-24 Months, based on time of enrollment
Title
Change in Neuro-QoL (Quality of Life) Short Form Scores -- General Concerns
Description
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.
Time Frame
Baseline, 18-24 Months, based on time of enrollment
Title
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Executive Function
Description
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.
Time Frame
Baseline, 18-24 Months, based on time of enrollment
Title
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Communication
Description
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.
Time Frame
Baseline, 18-24 Months, based on time of enrollment
Title
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Anxiety
Description
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.
Time Frame
Baseline, 18-24 Months, based on time of enrollment
Title
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Depression
Description
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.
Time Frame
Baseline, 18-24 Months, based on time of enrollment
Title
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Positive Affect and Well-Being
Description
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.
Time Frame
Baseline, 18-24 Months, based on time of enrollment
Title
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Emotional-Behavioral Dyscontrol
Description
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.
Time Frame
Baseline, 18-24 Months, based on time of enrollment
Title
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Satisfaction With Social Roles and Activities
Description
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.
Time Frame
Baseline, 18-24 Months, based on time of enrollment
Title
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Ability to Participate in Social Roles and Activities
Description
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.
Time Frame
Baseline, 18-24 Months, based on time of enrollment
Title
Change in SymptoMScreen Composite Score (SymptoMScreen - Overall Symptom Severity).
Description
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.
Time Frame
Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment. The change between baseline and Month 18-24 is reported.
Title
Change in Patient-Determined Disease Steps (PDDS - Disability).
Description
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.
Time Frame
Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment. The change between baseline and Month 18-24 is reported.
Title
Change in Symbol Digit Modalities Test (SDMT - Cognition).
Description
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.
Time Frame
Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment. The change between baseline and Month 18-24 is reported.
Title
Evaluation of the Patient's Quality of Life Using the MSIS-29 Scale -- Physical Impact
Description
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).
Time Frame
Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment. The change between baseline and Month 18-24 is reported.
Title
Evaluation of the Patient's Quality of Life Using the MSIS-29 Scale -- Psychological Impact
Description
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).
Time Frame
Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment. The change between baseline and Month 18-24 is reported.
Other Pre-specified Outcome Measures:
Title
Total Number of New T2 Lesions on MRI
Description
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.
Time Frame
Baseline, then every 6 months for 2 years with one exception at 18 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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.)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Corboy, MD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
University of Colorado Denver - Anschutz Medical Campus
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Georgetown University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66103
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Washington University St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63139
Country
United States
Facility Name
NYU Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Mt. Sinai University
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43221
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37215
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Swedish Health Services
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33990101
Citation
Hartung HP, Meuth SG, Miller DM, Comi G. Stopping disease-modifying therapy in relapsing and progressive multiple sclerosis. Curr Opin Neurol. 2021 Aug 1;34(4):598-603. doi: 10.1097/WCO.0000000000000960.
Results Reference
derived
PubMed Identifier
31368401
Citation
McGinley MP, Cola PA, Fox RJ, Cohen JA, Corboy JJ, Miller D. Perspectives of individuals with multiple sclerosis on discontinuation of disease-modifying therapies. Mult Scler. 2020 Oct;26(12):1581-1589. doi: 10.1177/1352458519867314. Epub 2019 Aug 1.
Results Reference
derived
Learn more about this trial
Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS)
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