Traditional Versus Early Aggressive Therapy for Multiple Sclerosis Trial (TREAT-MS)

February 28, 2024 updated by: Johns Hopkins University

A Pragmatic Trial to Evaluate the Intermediate-term Effects of Early, Aggressive Versus Escalation Therapy in People With Multiple Sclerosis

FDA-approved multiple sclerosis (MS) disease-modifying therapies (DMTs) target the relapsing phase of MS but have minimal impact once the progressive phase has begun. It is unclear if, in the relapsing phase, there is an advantage of early aggressive therapy with respect to preventing long-term disability. The infectious risks and other complications associated with higher-efficacy treatments highlight the need to quantify their effectiveness in preventing disability.

The TRaditional versus Early Aggressive Therapy for MS (TREAT-MS) trial is a pragmatic, randomized controlled trial that has two primary aims: 1) to evaluate, jointly and independently among patients deemed at higher risk vs. lower risk for disability accumulation, whether an "early aggressive" therapy approach, versus starting with a traditional, first-line therapy, influences the intermediate-term risk of disability, and 2) to evaluate if, among patients deemed at lower risk for disability who start on first-line MS therapies but experience breakthrough disease, those who switch to a higher-efficacy versus a new first-line therapy have different intermediate-term risk of disability.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

FDA-approved multiple sclerosis (MS) disease-modifying therapies (DMTs) target the relapsing phase of MS but have minimal impact once the progressive phase has begun. It is unclear if, in the relapsing phase, there is an advantage of early aggressive therapy with respect to preventing long-term disability. The infectious risks and other complications associated with higher-efficacy treatments highlight the need to quantify their effectiveness in preventing disability.

The TRaditional versus Early Aggressive Therapy for MS (TREAT-MS) trial is a pragmatic, randomized controlled trial that has two primary aims: 1) to evaluate, jointly and independently among patients deemed at higher risk vs. lower risk for disability accumulation, whether an "early aggressive" therapy approach, versus starting with a traditional, first-line therapy, influences the intermediate-term risk of disability, and 2) to evaluate if, among patients deemed at lower risk for disability who start on first-line MS therapies but experience breakthrough disease, those who switch to a higher-efficacy versus a new first-line therapy have different intermediate-term risk of disability.

Hypotheses/Objectives: The main hypothesis is that intermediate-term disability will be reduced by earlier use of higher-efficacy medications. Additional objectives include a) evaluating the magnitude of the treatment effect in patients deemed to be at higher risk versus lower risk of longer-term disability (we hypothesize that the effect size will be greater in the former group) and b) evaluating if, among those without indications of a high risk of longer-term disability, breakthrough disease can be successfully managed by switching to a different first-line therapy or if escalation is required at that time (we hypothesize that switching to a higher-efficacy therapy will be more effective in preventing disability in this group).

There is a great unmet need to identify the most appropriate treatment strategy for people with MS, especially early in the disease course when it may be possible to maximize an individual's chance for preventing long-term disability. There is a paucity of evidence-based guidelines to help clinicians, patients, and payers determine which treatment strategy is best for an individual with MS. Making treatment decisions is a daunting task, and the individualized benefit-risk assessment becomes increasingly difficult as new therapies emerge. Without the availability of direct comparative trials, clinicians and patients are forced to scrutinize observational studies that only provide basic insights into what may be the best treatment path moving forward. It is equally challenging to define what constitutes a suboptimal response to a DMT for an individual patient. Clinicians lack guidance on when to switch therapies and whether to consider a different first-line or if clinicians should escalate immediately to higher-efficacy therapies, so further consensus is needed to determine the optimal time to switch therapies and escalate therapy if an individual is on a first-line therapy from the start. The TREAT-MS trial will help inform patients and the broader health care community on whether patients would most benefit from early, possibly more risky aggressive therapy or if starting with a less aggressive (and, often, less risky) therapy, followed by a switch if breakthrough disease occurs, is warranted. In addition, this study may help identify specific patient populations and/or short-term clinical and paraclinical biomarkers that are strongly predictive of long-term disability that can ensue from MS.

Accrual of sustained disability is the most feared complication for people with MS, and the patient's own perception of their well-being or ill-being has a profound impact on their quality of life. The heterogeneity and unpredictability of MS, along with lack of agreed upon treatment guidelines, augments this fear, leading to a significant negative impact on quality of life. Even patients who are deemed to have "mild" MS experience a significant negative impact on their health-related quality of life that is similar in magnitude to what patients with other severe chronic conditions (i.e., congestive heart failure and chronic obstructive pulmonary disease) report. An extremely important goal for any intervention is to help improve or maintain a high quality of life; therefore, in addition to classic clinical endpoints (e.g. slowing disability progression), the TREAT-MS trial will capture several important and meaningful PROs that will shed light on what treatment strategies may be the best from a patient-centered perspective.

COVID-19 Related Substudy:

Since early 2020, the coronavirus disease 2019 (COVID-19) pandemic has caused clinical care and research disruptions nationwide, including for patients enrolled in the TREAT-MS trial. Many patients with MS, as well as their clinicians, are fearful that MS or the MS therapy they are using may increase the risk or severity of COVID-19 infection. Whether a person with early MS is more likely to experience more severe COVID-19 if treated with a higher-efficacy therapy is not known. Further, whether COVID-19-induced disruptions in therapy or other clinical care increase MS disease activity or MS symptoms is not clear but is relevant, particularly since greater MS activity in the early therapeutic course is associated in observational studies with worse long-term outcomes. Moreover, it is unclear if pre-pandemic anxiety and depression, common comorbidities in people with MS, contribute to decisions to delay care, overall or differently depending on therapeutic strategy (higher-efficacy vs. traditional). TREAT-MS provides an optimal cohort in which to investigate the effect of the COVID-19 pandemic on MS outcomes.

COVID-19 Substudy Aim 1. To evaluate if patients enrolled in TREAT-MS delayed or altered their disease-modifying therapy schedule or other MS care, and whether such alterations are associated with a greater degree of breakthrough inflammatory disease activity or the development of new (or worsening baseline) MS symptoms.

COVID-19 Substudy Aim 2: To evaluate if patients with MS treated with higher-efficacy, versus traditional, therapies differ in the risk of severe COVID-19 infection, defined as requiring hospitalization (with or without intubation) or mortality due to COVID-19.

Study Type

Interventional

Enrollment (Estimated)

900

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama at Birmingham
        • Contact:
        • Contact:
        • Principal Investigator:
          • William Meador, MD
      • Mobile, Alabama, United States, 36604
    • Arizona
      • Phoenix, Arizona, United States, 85013
    • California
      • Carmichael, California, United States, 95608
        • Recruiting
        • CommonSpirit Health Research Institute
        • Contact:
        • Principal Investigator:
          • Sabeen Lulu, MD
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai Medical Center
        • Principal Investigator:
          • Nancy Sicotte, MD
        • Contact:
      • Los Angeles, California, United States, 90095
        • Terminated
        • University of California, Los Angeles
      • San Diego, California, United States, 92037
        • Recruiting
        • University of California, San Diego
        • Contact:
        • Principal Investigator:
          • Jennifer S. Graves, MD, PhD, MAS
      • San Francisco, California, United States, 94158
        • Recruiting
        • University of California, San Francisco
        • Contact:
        • Principal Investigator:
          • Emmanuelle L Waubant, MD, PhD
        • Contact:
    • Delaware
      • Newark, Delaware, United States, 19713
        • Recruiting
        • Christiana Care Health Services, Inc.
        • Contact:
        • Principal Investigator:
          • Jason Silversteen, DO
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Recruiting
        • Georgetown University
        • Contact:
        • Principal Investigator:
          • Benjamin Osborne, MD
        • Contact:
    • Florida
      • Gainesville, Florida, United States, 32611
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami
        • Contact:
        • Principal Investigator:
          • Leticia Tornes, MD
        • Contact:
      • Tampa, Florida, United States, 33612
        • Recruiting
        • University of South Florida Health
        • Principal Investigator:
          • Derrick Robertson, MD
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • Rush University Medical Center
        • Principal Investigator:
          • Thomas Shoemaker, MD
        • Contact:
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • The University of Kansas Medical Center (KUMC)
        • Contact:
        • Principal Investigator:
          • Sharon Lynch, MD
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Withdrawn
        • University of Louisville
      • Louisville, Kentucky, United States, 40207
        • Recruiting
        • Norton Neurology MS Services
        • Contact:
        • Principal Investigator:
          • Geeta A Ganesh, MD, MPH
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • The Johns Hopkins Hospital
        • Principal Investigator:
          • Ellen M Mowry, MD, MCR
        • Principal Investigator:
          • Scott D Newsome, DO
        • Contact:
        • Contact:
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland, Baltimore
        • Contact:
        • Principal Investigator:
          • Daniel Harrison, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
        • Principal Investigator:
          • Eric C. Klawiter, MD, MSc
      • Worcester, Massachusetts, United States, 01655
        • Recruiting
        • University of Massachusetts Medical School
        • Contact:
        • Principal Investigator:
          • Carolina Ionete, MD
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Contact:
        • Principal Investigator:
          • Tiffany Braley, MD
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Wayne State University
        • Principal Investigator:
          • Evanthia Bernitsas, MD
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic
        • Contact:
        • Contact:
        • Principal Investigator:
          • W. Oliver Tobin, MB, BCh, BAO, PhD
    • Montana
      • Billings, Montana, United States, 59101
      • Great Falls, Montana, United States, 59405
        • Terminated
        • Advanced Neurology Specialists
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Recruiting
        • University of Nebraska Medical Center
        • Contact:
        • Principal Investigator:
          • Rana K Zabad, MD, FAAN
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Hackensack University Medical Center
        • Principal Investigator:
          • Krupa Pandey, MD
        • Contact:
      • Livingston, New Jersey, United States, 07039
        • Withdrawn
        • RWJBarnabas Health Multiple Sclerosis Comprehensive Care Center
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai
        • Contact:
        • Principal Investigator:
          • Ilana Katz Sand, MD
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Medical Center
        • Contact:
        • Principal Investigator:
          • Claire Riley, MD
      • New York, New York, United States, 10016
        • Recruiting
        • New York University School of Medicine
        • Principal Investigator:
          • Tyler Smith, MD
        • Contact:
      • Rochester, New York, United States, 14642
        • Withdrawn
        • University of Rochester Medical Center
      • Stony Brook, New York, United States, 11794-8121
        • Withdrawn
        • Stony Brook University
    • North Carolina
      • Charlotte, North Carolina, United States, 28207
        • Withdrawn
        • Novant Health Neurology and Sleep
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Active, not recruiting
        • University of Cincinnati
      • Columbus, Ohio, United States, 43214
        • Recruiting
        • OhioHealth Research Institute
        • Contact:
        • Principal Investigator:
          • Geoffrey Eubank, MD
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • Oklahoma Medical Research Foundation
        • Contact:
        • Principal Investigator:
          • Gabriel Pardo, MD
    • Oregon
      • Portland, Oregon, United States, 97225
        • Recruiting
        • Providence Health and Services - Oregon
        • Contact:
        • Principal Investigator:
          • Stanley Cohan, MD, PhD
        • Contact:
    • Pennsylvania
      • Danville, Pennsylvania, United States, 17822
        • Recruiting
        • Geisinger Clinic
        • Contact:
        • Contact:
        • Principal Investigator:
          • Megan Esch, MD
      • Pittsburgh, Pennsylvania, United States, 15212
        • Recruiting
        • Allegheny Health Network Research Institute
        • Principal Investigator:
          • Troy Desai, MD
        • Contact:
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37215
        • Recruiting
        • Vanderbilt Comprehensive MS Center
        • Principal Investigator:
          • Siddharama Pawate, MD
        • Contact:
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75246
        • Terminated
        • Baylor Scott and White Health
      • Dallas, Texas, United States, 75390-8806
      • Round Rock, Texas, United States, 78681
        • Active, not recruiting
        • Central Texas Neurology Consultants
    • Utah
      • Salt Lake City, Utah, United States, 84108
        • Recruiting
        • University of Utah
        • Contact:
        • Principal Investigator:
          • John W Rose, MD
    • Vermont
      • Burlington, Vermont, United States, 05405
        • Recruiting
        • The University of Vermont and State Agricultural College
        • Principal Investigator:
          • Andrew Solomon, MD
        • Contact:
    • Virginia
      • Christiansburg, Virginia, United States, 24073
        • Recruiting
        • Blacksburg Neurology
        • Contact:
        • Principal Investigator:
          • Jill Cramer, MD
      • Norfolk, Virginia, United States, 23502
        • Terminated
        • Neurology Consultants of Tidewater
    • Washington
      • Seattle, Washington, United States, 98122
        • Recruiting
        • Swedish Health Services
        • Contact:
        • Principal Investigator:
          • Peiqing Qian, MD
      • Seattle, Washington, United States, 98133
        • Recruiting
        • University of Washington
        • Contact:
        • Principal Investigator:
          • Gloria von Geldern, MD
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin
        • Contact:
        • Principal Investigator:
          • Ahmed Obeidat, MD
        • Contact:
          • Samantha O'Dell, BA
          • Phone Number: 414-955-0628
          • Email: sodell@mcw.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Aged 18-60 years
  • Meets 2017 McDonald criteria for relapsing-remitting MS [patients with clinically isolated syndrome (CIS) are not eligible]
  • Must be EITHER John Cunningham (JC) virus antibody negative or low positive (index antibody titer <0.9), OR negative for: Hepatitis B and C, tuberculosis
  • HIV negative
  • No chemotherapy in past year; if patient has prior history of chemotherapy or malignancy, documentation in chart explaining why potential risks of higher-efficacy therapy are justified

Exclusion Criteria:

  • Prior treatment with rituximab, ocrelizumab, ofatumumab, alemtuzumab, mitoxantrone or cladribine
  • Prior treatment with any other MS DMT for more than 6 months
  • Prior treatment with experimental aggressive therapies (e.g., T-cell vaccine, total lymphoid radiation, stem cells)
  • Treatment with teriflunomide within past 2 years (even for ≤ 6 months), unless rapid wash out done (i.e., with cholestyramine or activated charcoal)
  • Treatment in the past 6 months with any MS DMT
  • Prior treatment with any other investigational immune-modulating /suppressing drug for MS not listed above
  • Pregnant or breast-feeding
  • Women of child-bearing age who are planning or strongly considering conception during the study time frame

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Early Aggressive Therapy

Higher efficacy disease-modifying therapy (Early Aggressive Therapy) for treatment of multiple sclerosis

Early Aggressive Therapy choices and maximum allowable doses:

  • Natalizumab (Tysabri), 300 mg IV every 4 wks
  • Alemtuzumab (Lemtrada), 12 mg IV daily (QD) for 5 days; 1 year later: 12 mg IV QD for 3 days
  • Ocrelizumab (Ocrevus), 300 mg IV every 2 wks (for 2 doses) at initiation; then 600 mg IV every 6 mths
  • Rituximab (Rituxan), 1000 mg IV every 2 wks (for 2 doses); may repeat every 16-24 wks
  • Cladribine (Mavenclad), 3.5 mg per kg body weight orally divided into 2 yrly treatment courses (1.75 mg per kg body weight each year); each yrly treatment course is divided into 2 treatment cycles; administer cycle dosage as 1 or 2 tablets QD over 4-5 consecutive days
  • Ofatumumab (Kesimpta), 20 mg SC wkly for wks 0, 1 and 2; 20 mg subcutaneously (SC) monthly starting at wk 4
  • Ublituximab-xiiy (Briumvi), 150 mg IV (first dose); 450 mg IV 2 wks after first dose; 450 mg IV q 24 wks
Other: Natalizumab, Alemtuzumab, Ocrelizumab, Rituximab, Cladribine, Ofatumumab, Ublituximab-xiiy
Early Aggressive Therapy
Other Names:
  • Tysabri, Lemtrada, Ocrevus, Rituxan, Mavenclad, Kesimpta, Briumvi
Active Comparator: Traditional Therapy

First-line disease-modifying therapy (Traditional Therapy) for treatment of multiple sclerosis

Traditional Therapy choices and maximum allowable doses:

  • Glatiramer acetate (Copaxone, Glatopa, and other generics), 20 mg SC daily, or 40 mg SC 3 times a wk
  • Intramuscular (IM) interferon (Avonex), 30 mcg IM weekly
  • SC interferon (Betaseron, Extavia, Rebif), 0.25 mg SC every other day (Betaseron, Extavia); 44 mcg SC 3 times a wk (Rebif)
  • Pegylated interferon (Plegridy), 125 mcg SC every 14 days
  • Teriflunomide (Aubagio), 14 mg PO QD
  • Dimethyl fumarate (Tecfidera and generics), 240 mg PO twice a day (BID)
  • Diroximel fumarate (Vumerity), 462 mg PO BID
  • Monomethyl fumarate (Bafiertam), 190 mg PO BID
  • Fingolimod (Gilenya and generics), 0.5 mg PO QD
  • Siponimod (Mayzent), 1 mg PO QD or 2 mg PO QD
  • Ozanimod (Zeposia), 0.92 mg PO QD
  • Ponesimod (Ponvory), 20 mg PO QD
  • Fingolimod ODT (Tascenso), 0.25 mg PO QD if <=40 kg; 0.5 mg PO QD if > 40 kg
Other: Glatiramer acetate, Interferons (intramuscular, subcutaneous, pegylated) Teriflunomide, Fumarates (dimethyl, diroximel, monomethyl) Fingolimod, Siponimod, Ozanimod, Ponesimod
Traditional Therapy
Other Names:
  • Copaxone, Glatopa, Avonex, Betaseron, Extavia, Rebif, Plegridy, Aubagio, Tecfidera, Vumerity, Bafiertam, Gilenya, Mayzent, Zeposia, Ponvory, Tascenso

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to sustained disability progression
Time Frame: From date of randomization until the date of first documented sustained disability progression, up to 75 months
Time to sustained disability progression is measured by the Expanded Disability Status Scale plus (EDSS+): a composite endpoint that includes EDSS change (change at any 6 month time point of > 1.0 point if baseline EDSS is < 5.5 or of > 0.5 if baseline EDSS is > 6.0, that is sustained 6 months later) OR 20% worsening on either of two specific components of the Multiple Sclerosis Functional Composite (MSFC), the timed 25-foot walk test (T25FWT) and the nine hole peg test (9HPT) that is sustained 6 months later.
From date of randomization until the date of first documented sustained disability progression, up to 75 months
Change in Overall Burden of MS
Time Frame: up to 48 weeks from enrollment into COVID-19 related substudy
The change in overall burden of MS will be defined for the COVID-19 related substudy as the occurrence of breakthrough disease (relapses or new MRI activity) or the development of new (or worsening baseline) MS symptoms, which are (for TREAT-MS) and will continue to be (during the substudy) documented at clinical visits, whether in-person or on tele-visits.
up to 48 weeks from enrollment into COVID-19 related substudy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Severe COVID-19 Infection
Time Frame: up to 48 weeks from enrollment into COVID-19 related substudy
Severe COVID-19 infection will be defined as an outcome of "hospitalization or death" due to confirmed or suspected COVID-19 infection
up to 48 weeks from enrollment into COVID-19 related substudy
Patient-Determined Disease Steps (PDDS)
Time Frame: up to 87 months
PDDS is a self-assessment scale of disability due to MS on a scale from 0 to 8 and will be administered as an electronic patient-reported outcome (PRO).
up to 87 months
Multiple Sclerosis Functional Composite (MSFC) Composite Score
Time Frame: up to 87 months
The MSFC consists of the timed 25 foot walk test, the 9-hole peg test, and the Paced Auditory Serial Addition Test (PASAT) and a composite MSFC z-score will be evaluated.
up to 87 months
Timed 25 Foot Walk Test
Time Frame: up to 87 months
Time taken to complete the timed 25 foot walk test, measured twice in units of seconds, will be averaged and evaluated.
up to 87 months
Nine-hole Peg Test
Time Frame: up to 87 months
Time taken to complete the nine-hole peg test, measured twice for each hand (dominant and non-dominant) in units of seconds, will be averaged for each hand and evaluated.
up to 87 months
Paced Auditory Serial Addition Test (PASAT)
Time Frame: up to 87 months
The paced auditory serial addition test that measures processing speed will be administered once; number and percent correct will be evaluated.
up to 87 months
Low contrast visual acuity
Time Frame: up to 87 months
Low-contrast letter acuity (binocular, 2.5% contrast Sloan charts)
up to 87 months
Patient-reported incomplete relapse recovery
Time Frame: up to 87 months
Among participants identified to have a relapse, relapse recovery will be defined as complete or incomplete based on patient self-report.
up to 87 months
Neurologic exam-based incomplete relapse recovery
Time Frame: up to 87 months
Among participants identified to have a relapse, relapse recovery will be defined as complete or incomplete based on neurologic examination (those who have increased Functional System scores, corresponding to the relapse symptoms, of 1.0 point or greater for at least 6 months after the relapse onset, without subsequent accrual of worsening in that same Functional System (e.g. more indicative of progression), will be considered to have incomplete relapse recovery).
up to 87 months
Cognition using Symbol Digit Modality Test (SDMT)
Time Frame: up to 87 months
The SDMT is commonly used in MS to assess processing speed and will be administered orally and used to evaluate changes in cognition throughout the study.
up to 87 months
Multiple Sclerosis Impact Scale (MSIS-29)
Time Frame: up to 87 months
The MSIS-29 will be used to evaluate the impact of MS on the participants and will be administered as an electronic PRO.Multiple Sclerosis Impact Scale (MSIS-29) is an instrument used for measuring the physical (20 items) and psychological (nine items) impact of multiple sclerosis.
up to 87 months
Quality of Life in Neurological Disorders (Neuro-QoL): Anxiety Subscale
Time Frame: up to 87 months
The Anxiety Subscale of Neuro-QoL will be administered as an electronic PRO.
up to 87 months
Quality of Life in Neurological Disorders (Neuro-QoL): Depression Subscale
Time Frame: up to 87 months
The Depression Subscale of Neuro-QoL will be administered as an electronic PRO.
up to 87 months
Quality of Life in Neurological Disorders (Neuro-QoL): Fatigue Subscale
Time Frame: up to 87 months
The Fatigue Subscale of Neuro-QoL will be administered as an electronic PRO.
up to 87 months
Quality of Life in Neurological Disorders (Neuro-QoL): Upper Extremity Function
Time Frame: up to 87 months
The Upper Extremity Function Subscale of Neuro-QoL will be administered as an electronic PRO.
up to 87 months
Quality of Life in Neurological Disorders (Neuro-QoL): Lower Extremity Function
Time Frame: up to 87 months
The Lower Extremity Function Subscale of Neuro-QoL will be administered as an electronic PRO.
up to 87 months
Quality of Life in Neurological Disorders (Neuro-QoL): Cognitive Function
Time Frame: up to 87 months
The Cognitive Function Subscale of Neuro-QoL will be administered as an electronic PRO.
up to 87 months
Quality of Life in Neurological Disorders (Neuro-QoL): Positive Affect/Well-being
Time Frame: up to 87 months
The Positive Affect/Well-being Subscale of Neuro-QoL will be administered as an electronic PRO.
up to 87 months
Quality of Life in Neurological Disorders (Neuro-QoL): Sleep Disturbance
Time Frame: up to 87 months
The Sleep Disturbance Subscale of Neuro-QoL will be administered as an electronic PRO.
up to 87 months
Quality of Life in Neurological Disorders (Neuro-QoL): Ability to Participate in Social Roles and Activities
Time Frame: up to 87 months
The Ability to Participate in Social Roles and Activities Subscale of Neuro-QoL will be administered as an electronic PRO.
up to 87 months
Quality of Life in Neurological Disorders (Neuro-QoL): Satisfaction with Social Roles and Activities
Time Frame: up to 87 months
The Satisfaction with Social Roles and Activities Subscale of Neuro-QoL will be administered as an electronic PRO.
up to 87 months
Quality of Life in Neurological Disorders (Neuro-QoL): Stigma
Time Frame: up to 87 months
The Stigma Subscale of Neuro-QoL will be administered as an electronic PRO.
up to 87 months
Employment status
Time Frame: up to 87 months
The incidence of change in employment to "disabled" or "looking for work, unemployed," will be evaluated for all participants through an electronic PRO.
up to 87 months
Marital status
Time Frame: up to 87 months
Incident divorce or separation, among those who previously were married or in a domestic partnership, will be evaluated for all participants through an electronic PRO.
up to 87 months
Serious Adverse Events (SAEs)
Time Frame: up to 87 months
SAEs (clinically significant infections, malignancies, or the development of other serious comorbidities, as well as unplanned hospitalizations [for non-elective issues, excluding MS relapse] and death)
up to 87 months
Adverse event resulting in a decision to change disease-modifying therapy
Time Frame: up to 87 months
Adverse events meaningful enough to lead to medication discontinuation
up to 87 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain Magnetic Resonance Imaging (MRI) evidence of neurodegeneration
Time Frame: From 6 months after starting 1st therapy up to 87 months after randomization
Changes in brain MRI measures of neurodegeneration, including whole brain and normalized gray matter volumes, cortical thickness, subcortical gray matter compartment volumes, and measures of T2 lesion burden.
From 6 months after starting 1st therapy up to 87 months after randomization
Number of relapses
Time Frame: up to 87 months
The number of relapses (new or worsening neurologic symptoms lasting for 24 hours or more in the absence of fever).
up to 87 months
Number of new brain lesions on MRI
Time Frame: up to 87 months
The number of new/enlarging T2-weighted hyperintense lesions and T1-weighted hypointense lesions will be quantified on each MRI scan
up to 87 months
Retinal layer thickness by Optical Coherence Tomography (OCT)
Time Frame: up to 87 months
Retinal nerve fiber layer and ganglion cell/inner plexiform thickness will be evaluated among patients at centers and offices with access to OCT as standard of care
up to 87 months
Number of new medications, escalated dosage of medications, and non-pharmacologic interventions for MS-related symptoms
Time Frame: up to 87 months
As an exploratory outcome, the number of newly-prescribed or dose-escalated medications used for treating MS symptoms (including pain, weakness, numbness/tingling, trouble walking, cognitive problems, fatigue, depression, anxiety, visual dysfunction, spasticity, vertigo, or bladder/bowel/sexual dysfunction) during the trial will be evaluated using the electronic health record. In addition, non-pharmacologic interventions (and referrals to other healthcare providers) for symptom management will also be captured.
up to 87 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Collaborators

Patient-Centered Outcomes Research Institute
National Multiple Sclerosis Society

Investigators

  • Principal Investigator: Ellen M. Mowry, MD, MCR, Johns Hopkins University
  • Principal Investigator: Scott D. Newsome, DO, Johns Hopkins University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 2, 2018

Primary Completion (Estimated)

August 1, 2025

Study Completion (Estimated)

August 1, 2025

Study Registration Dates

First Submitted

February 21, 2018

First Submitted That Met QC Criteria

April 12, 2018

First Posted (Actual)

April 18, 2018

Study Record Updates

Last Update Posted (Actual)

March 1, 2024

Last Update Submitted That Met QC Criteria

February 28, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00143534

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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