Multiple SclerosisPhase 4DISCOMSNCT03073603

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

A Phase 4 study testing Discontinuation of disease modifying therapy in people with Multiple Sclerosis, run by University of Colorado, Denver at 19 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 55 years and older
Conditions the study is for: Multiple Sclerosis
What is being tested?: Discontinuation of disease modifying therapy
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 259 participants
Where: 19 sitesUnited States
Study dates: 20 Apr 2017to 31 Aug 2021
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 55 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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;

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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).

Who cannot join

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.

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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.)

Trial locations and contacts

19 sites in 1 country.

City, postcode or hospital

19 sites in 1 country

United States19 sites

University of Colorado Denver - Anschutz Medical Campus
Aurora, Colorado, 80045
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Virginia
Charlottesville, Virginia, 22908
Cleveland Clinic
Cleveland, Ohio, 44195
The Ohio State University
Columbus, Ohio, 43221
University of Kansas Medical Center
Kansas City, Kansas, 66103
University of Southern California
Los Angeles, California, 90033
University of Miami
Miami, Florida, 33136
Vanderbilt University
Nashville, Tennessee, 37215
NYU Langone Medical Center
New York, New York, 10016
Mt. Sinai University
New York, New York, 10029
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Oregon Health and Science University
Portland, Oregon, 97239
University of Rochester
Rochester, New York, 14642
Swedish Health Services
Seattle, Washington, 98122
Washington University St. Louis
St Louis, Missouri, 63139
Georgetown University
Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

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.

Read the 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.

Conditions: Multiple Sclerosis
Being tested: Discontinuation of disease modifying therapy, Standard of Care
Medical subject headings: Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Discontinuation of disease modifying therapyDrug
Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Standard of CareDrug
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.

Study groups in NCT03073603
Study group	Role	What they receive
Drug Continuation Arm	Active comparator	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. Receives: Drug: Standard of Care
Drug Discontinuation Arm	Experimental	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. Receives: Drug: Discontinuation of disease modifying therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 18-24 months, based on time of enrollment

Secondary outcomes (19)

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.
Measured: Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment.
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.
Measured: Baseline, 18-24 Months, based on time of enrollment
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.
Measured: Baseline, 18-24 Months, based on time of enrollment
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.
Measured: Baseline, 18-24 Months, based on time of enrollment
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.
Measured: Baseline, 18-24 Months, based on time of enrollment
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.
Measured: Baseline, 18-24 Months, based on time of enrollment
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.
Measured: Baseline, 18-24 Months, based on time of enrollment
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.
Measured: Baseline, 18-24 Months, based on time of enrollment
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.
Measured: Baseline, 18-24 Months, based on time of enrollment
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.
Measured: Baseline, 18-24 Months, based on time of enrollment
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.
Measured: Baseline, 18-24 Months, based on time of enrollment
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.
Measured: Baseline, 18-24 Months, based on time of enrollment
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.
Measured: Baseline, 18-24 Months, based on time of enrollment
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.
Measured: Baseline, 18-24 Months, based on time of enrollment
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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).
Measured: 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.
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).
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Apr 201731 Aug 2021

First posted8 Mar 2017
Study start20 Apr 2017
Primary completion31 Aug 2021
Study completion31 Aug 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Multiple SclerosisStudies of the same condition, open and under way.
More trials run by University of Colorado, DenverThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 259 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03073603
Sponsor's protocol ID: 15-2388
Acronym: DISCOMS
Status last verified: Aug 2023
First submitted: 18 Jan 2017
Last updated: 16 Aug 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Ben-Zacharia AB, Cutter G, Shor A, Morgan C, Engebretson E, Corboy J, Strauss SM. The association between BMI and cognition, disability, and quality of life markers in multiple sclerosis: DISCOMS secondary analysis. Ther Adv Neurol Disord. 2026 Aug 31;19:17562864261463625. doi: 10.1177/17562864261463625. eCollection 2026.
PubMed 42682723
Corboy JR, Fox RJ, Kister I, Cutter GR, Morgan CJ, Seale R, Engebretson E, Gustafson T, Miller AE; DISCOMS investigators. Risk of new disease activity in patients with multiple sclerosis who continue or discontinue disease-modifying therapies (DISCOMS): a multicentre, randomised, single-blind, phase 4, non-inferiority trial. Lancet Neurol. 2023 Jul;22(7):568-577. doi: 10.1016/S1474-4422(23)00154-0.
PubMed 37353277
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.
PubMed 33990101
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.
PubMed 31368401

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 16 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS)
ClinicalTrials.gov ID: NCT03073603
Acronym / sponsor ID: DISCOMS / 15-2388
Conditions: Multiple Sclerosis
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 259 participants (actual)
Lead sponsor: University of Colorado, DenverUniversity, hospital or other
Collaborators: Patient-Centered Outcomes Research Institute, National Multiple Sclerosis Society, University of Alabama at Birmingham
Study start: 20 Apr 2017 (actual)
Primary completion: 31 Aug 2021 (actual)
Study completion: 31 Aug 2021 (actual)
First posted: 8 Mar 2017 (actual)
Results: Posted 6 Oct 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Drug Continuation Arm	Active comparator	Drug: Standard of CareParticipants 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 Discontinuation Arm	Experimental	Drug: Discontinuation of disease modifying therapyParticipants 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.

Who may qualify

Ages: 55 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (21 listed)

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:
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

Key exclusion criteria (26 listed)

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.
Prior use of the following in the past 5 years:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Discontinuation of disease modifying therapyParticipants who will discontinue their current MS drug. No other changes to their treatment occur.	Drug	Drug Discontinuation Arm
Standard of CareParticipants 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	Drug Continuation Arm

Primary outcome

Number 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.

19 secondary outcomes

Number With Disability Progression Confirmed at 6 Months 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.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Upper Extremity Function
Time frame: Baseline, 18-24 Months, based on time of enrollment
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Lower Extremity Function
Time frame: Baseline, 18-24 Months, based on time of enrollment
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Fatigue
Time frame: Baseline, 18-24 Months, based on time of enrollment
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Sleep Disturbance
Time frame: Baseline, 18-24 Months, based on time of enrollment
Change in Neuro-QoL (Quality of Life) Short Form Scores -- General Concerns
Time frame: Baseline, 18-24 Months, based on time of enrollment
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Executive Function
Time frame: Baseline, 18-24 Months, based on time of enrollment
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Communication
Time frame: Baseline, 18-24 Months, based on time of enrollment
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Anxiety
Time frame: Baseline, 18-24 Months, based on time of enrollment
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Depression
Time frame: Baseline, 18-24 Months, based on time of enrollment
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Positive Affect and Well-Being
Time frame: Baseline, 18-24 Months, based on time of enrollment
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Emotional-Behavioral Dyscontrol
Time frame: Baseline, 18-24 Months, based on time of enrollment
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Satisfaction With Social Roles and Activities
Time frame: Baseline, 18-24 Months, based on time of enrollment
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Ability to Participate in Social Roles and Activities
Time frame: Baseline, 18-24 Months, based on time of enrollment
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. The change between baseline and Month 18-24 is reported.
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. The change between baseline and Month 18-24 is reported.
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 change between baseline and Month 18-24 is reported.
Evaluation of the Patient's Quality of Life Using the MSIS-29 Scale -- Physical Impact
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.
Evaluation of the Patient's Quality of Life Using the MSIS-29 Scale -- Psychological Impact
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.

Results and safety

Results posted to the registry on 6 Oct 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Drug Continuation Arm	128	106
Drug Discontinuation Arm	131	123

Primary outcome: Number 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. Count of participants. Unit: Participants

Measure	Drug Continuation Arm n = 128	Drug Discontinuation Arm n = 131
Value	6	16

Drug Continuation Arm vs Drug Discontinuation Arm: Difference in proportion: 0.0753 (95% CI 0.0063 to 0.1500), p = 0.521, Exact binomial test

19 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline to end of study (24 months). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Drug Continuation Arm	1 of 128 (0.8%)	66 of 128 (51.6%)	1 of 128
Drug Discontinuation Arm	1 of 131 (0.8%)	70 of 131 (53.4%)	2 of 131

Limitations and caveats (from the sponsor): Mostly white women; all participants in US; Relatively short follow-up (maximum 2 years); Most participants using older, injectable therapies for MS; Small numbers don't allow for significant subgroup analysis, eg not enough on high efficacy medications; Being a pragmatic study (real-world, insurance paid for MRI scans), and COVID pandemic resulted in more missing data than desirable; No brain volume data, a meaningful measure; No NfL or other serum or spinal fluid biomarker data.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42682723Ben-Zacharia AB, Cutter G, Shor A, Morgan C, Engebretson E, Corboy J, Strauss SM. The association between BMI and cognition, disability, and quality of life markers in multiple sclerosis: DISCOMS secondary analysis. Ther Adv Neurol Disord. 2026 Aug 31;19:17562864261463625. doi: 10.1177/17562864261463625. eCollection 2026.
Derived from this study: PubMed 37353277Corboy JR, Fox RJ, Kister I, Cutter GR, Morgan CJ, Seale R, Engebretson E, Gustafson T, Miller AE; DISCOMS investigators. Risk of new disease activity in patients with multiple sclerosis who continue or discontinue disease-modifying therapies (DISCOMS): a multicentre, randomised, single-blind, phase 4, non-inferiority trial. Lancet Neurol. 2023 Jul;22(7):568-577. doi: 10.1016/S1474-4422(23)00154-0.
Derived from this study: PubMed 33990101Hartung 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.
Derived from this study: PubMed 31368401McGinley 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

John Corboy, MD principal investigator

University of Colorado, Denver

19 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Discontinuation of disease modifying therapy in people with Multiple Sclerosis, run by University of Colorado, Denver at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03073603, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2023.