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

This study is currently recruiting participants.
Verified October 2017 by University of Colorado, Denver
Sponsor:
ClinicalTrials.gov Identifier:
NCT03073603
First Posted: March 8, 2017
Last Update Posted: October 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Patient-Centered Outcomes Research Institute
National Multiple Sclerosis Society
University of Alabama at Birmingham
Information provided by (Responsible Party):
University of Colorado, Denver
  Purpose
Natural history research in MS suggests that risk of relapses and new Magnetic Resonance Imaging (MRI) changes diminish significantly as people age, especially in MS patients 55 or older. Thus, the need to continue MS medicines that reduce relapses and new MRI lesions may also decrease as people age, especially in those who have not had relapses or MRI scan changes for prolonged times. This study plans to learn more about the safety of stopping MS medication in this population, as compared to continuing on the medication.

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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS)

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Number of patients with new disease activity upon discontinuation of therapy vs. those continuing therapy. [ Time Frame: Baseline, then every 6 months for 2 years with one exception at 18 months. ]
    In multiple sclerosis patients 55 years of age or older who have not had a new relapse or brain MRI scan change for at least five years while continuously taking a disease modifying therapy, the risk of having a new relapse or brain MRI lesion is no higher over a two year period of time in those who discontinue vs. those who continue disease modifying therapy.


Secondary Outcome Measures:
  • Evaluation of the patient's Quality of Life using the MSIS-29 Scale [ Time Frame: Baseline, then every 6 months for 2 years. ]
    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 the 4 indicated extremely impacted. The lower the final score, the less impacted the participant is overall. We will compare the groups for those who have had a change of eight points or more (considered a meaningful change) over the two years of the study.

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

  • Evaluation of Change in Physical Disability using the Expanded Disability Status Scale (EDSS) [ Time Frame: Baseline, then every 6 months for 2 years. ]
    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, with a change confirmed six months later considered to be significant. We will assess percentage of those who have had such a confirmed change at six months, anytime over the two year period of the study.


Other Outcome Measures:
  • Evaluation of the Patient's Disability using Patient-Determined Disease Steps [ Time Frame: Baseline, then every 6 months for 2 years. ]
    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.


Estimated Enrollment: 300
Actual Study Start Date: April 20, 2017
Estimated Study Completion Date: February 2021
Estimated Primary Completion Date: February 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Drug Continuation Arm
Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include ~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.
Drug: Standard of Care
Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include ~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.
Experimental: Drug Discontinuation Arm
Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include ~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.
Drug: Discontinuation of disease modifying therapy
Participants who will discontinue their current MS drug. No other changes to their treatment occur.

Detailed Description:

This study will have 2 different groups of research subjects. One of these groups will stay on their current MS medication, and one group will discontinue their medication. To decide which group the participant will be in, the investigators will use a method of chance. This method is like flipping a coin or rolling dice. This is called "randomization".

Participants will be randomized to one of the 2 groups as described above. They will also have some extra assessments done at their regular routine MS clinic appointment and every 6 months for the next 2 years. The following items will be done in addition to any assessments or procedures they are already having done as part of their clinical care and are the only items to be paid for by the study:

  • Some questionnaires about the participant's quality of life including questions about health, mood, thinking, and social life
  • Some questionnaires about the participant's MS symptoms
  • A test of the participant's attention, concentration, and thinking that involves adding and repeating numbers
  • A test of the participant's physical symptoms
  • Along with the MRIs the participants get as part of their routine care, they will also have one 6 months from their start in the study as part of the study.
  Eligibility

Information from the National Library of Medicine

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


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

Inclusion Criteria:

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

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

    • interferon β-1a,
    • interferon β-1b,
    • glatiramer acetate,
    • natalizumab,
    • fingolimod,
    • dimethyl fumarate, 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 5 years (at least 2 scans separated by at least 5 years must be reviewed) on brain or spine MRI scan
  • Significant (as defined by the PI) intolerance of presently-used DMT
  • Use of any non-FDA-approved DMT or systemic corticosteroids 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 10 years:

    • alemtuzumab,
    • mitoxantrone,
    • cyclophosphamide,
    • methotrexate,
    • cyclosporine, or
    • rituximab
  • 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 10 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.)
  Contacts and Locations
Information from the National Library of Medicine

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

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03073603


Contacts
Contact: Eric Engebretson, BA 303-724-8388 eric.engebretson@ucdenver.edu
Contact: Nicola Haakonsen, BS 303-724-6351 NICOLA.HAAKONSEN@UCDENVER.EDU

Locations
United States, Colorado
University of Colorado Denver - Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Nicola Haakonsen, B.S.    303-724-4644    NICOLA.HAAKONSEN@UCDENVER.EDU   
United States, District of Columbia
Georgetown University Not yet recruiting
Washington, D.C., District of Columbia, United States, 20007
Contact: Alexis Ahmad    202-444-2658    asc73@georgetown.edu   
United States, Florida
University of Miami Not yet recruiting
Miami, Florida, United States, 33136
Contact: Yanet Babcock    305-243-1088    ybabcock@med.miami.edu   
United States, Missouri
Washington University St. Louis Recruiting
Saint Louis, Missouri, United States, 63139
Contact: Courtney Dula    314-362-3402    dulac@wustl.edu   
United States, New York
NYU Langone Medical Center Recruiting
New York, New York, United States, 10016
Contact: Allyson Reid    646-501-7534    Allyson.Reid@nyumc.org   
Mt. Sinai University Recruiting
New York, New York, United States, 10029
Contact: Hennesys Disla    212-241-5329    hennesys.disla1@mssm.edu   
University of Rochester Recruiting
Rochester, New York, United States, 14642
Contact: Cindy Irish    585-275-6120    Cindy_Irish@URMC.Rochester.edu   
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Sneha Natarajan       Nataras@ccf.org   
The Ohio State University Recruiting
Columbus, Ohio, United States, 43221
Contact: Stephanie Scarberry    614-688-4678    Stephanie.Scarberry@osumc.edu   
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Anna Orban    503-494-3549    orban@ohsu.edu   
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Ashley Pinckney    215-349-5162    Ashley.Pinckney@uphs.upenn.edu   
Thomas Jefferson University Not yet recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Alexa Snively-Bologna    215-955-9575    Alexa.Snively-Bologna@jefferson.edu   
University of Pittsburgh Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Kerry Oddis    412-692-4918    oddikm@mail.magee.edu   
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37215
Contact: Jennifer Scott    615-322-4085    Jennifer.L.scott@vanderbilt.edu   
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Rachael Coleman    434-924-5717    RC4KZ@hscmail.mcc.virginia.edu   
Sponsors and Collaborators
University of Colorado, Denver
Patient-Centered Outcomes Research Institute
National Multiple Sclerosis Society
University of Alabama at Birmingham
Investigators
Principal Investigator: John Corboy, MD University of Colorado, Denver
  More Information

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT03073603     History of Changes
Other Study ID Numbers: 15-2388
First Submitted: January 18, 2017
First Posted: March 8, 2017
Last Update Posted: October 12, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases