Cognitive Markers in Prodromal MS

NYU Langone Health (Other)
Overall Status
Recruiting ID
National Multiple Sclerosis Society (Other)

Study Details

Study Description

Brief Summary

The focus of this work is the evaluation of a measure of cognitive functioning- intra-individual variability (IIV) - derived from a computer-based continuous reaction time (RT) task (Cogstate) as an early marker of prodromal MS.

Condition or Disease Intervention/Treatment Phase
  • Device: Active tDCS

Detailed Description

This study is a prospective observational clinical study, where the researchers will recruit adults with early MS (n=60) to complete a cognitive assessment and an optional gait assessment using Runscribe and G-sensor. Thirty-five [35] participants will also have a single 60-minute investigational MRI combined with 20 minutes of simultaneous tDCS. The MRI will repeat the protocol from the researchers' current study ( Identifier: NCT03564496, IRB i18-00548) using simultaneous transcranial direct current stimulation (tDCS) during the imaging acquisition.

Study Design

Study Type:
Anticipated Enrollment :
50 participants
Intervention Model:
Parallel Assignment
None (Open Label)
Primary Purpose:
Official Title:
Intra-Individual Variability in Cognitive Performance as a Marker of Prodromal Disability in MS
Actual Study Start Date :
Jan 18, 2022
Anticipated Primary Completion Date :
Jun 18, 2024
Anticipated Study Completion Date :
Jun 18, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Group with tDCS-MRI

Participants will have a cognitive assessment, an optional gait assessment, and a 1-hour MRI brain scan combined with 20 minutes of simultaneous tDCS. Participants may also complete the MRI on a separate visit.

Device: Active tDCS
The tDCS-MRI scan will last approximately one hour. The first 20 minutes of the MRI will not include tDCS stimulation. After 20 minutes, the tDCS device will ramp up to 2.0mA and deliver 2.0mA for 20 minutes. Then the tDCS will ramp down (30 seconds) and the final 20 minutes will be without stimulation.

No Intervention: Group without tDCS- MRI

Participants will have include a cognitive assessment and an optional gait assessment

Outcome Measures

Primary Outcome Measures

  1. Cerebral metabolic rate of oxygen (CMRO2) [4 minutes]

    To quantify absolute CMRO2, both TRUST MRI for quantification of venous oxygenation (Yv) and phase contrast (PC) MRI for quantification of total blows are needed. The total scan time for CMRO2 MRI is approximately 4 minutes.

  2. Intra-Individual Variability (IIV) as measured by Cogstate Brief Battery (CBB) [Day 1 (Visit 1)]

    The core Cogstate RT tasks involve a deck of cards on a green background screen and the participant answers "yes" or "no" by hitting a keyboard key ("D" or "K") across repeated trials. Each task first includes instructions and practice period before the test begins and takes approximately 3-4 minutes to complete (for a total of ~7 minutes). The representative timed RT scores are provided by the Detection task (indicating when a card is revealed; DET/simple RT), Identification task ("is the card revealed black or red?"; IDN/choice RT), and One-Back ("Is this the card that you just saw?"). Performance is characterized by near complete accuracy (i.e. all, or almost all, items are answered correctly), and validity checks are built into the scoring. IIV is calculated as intraindividual standardized deviations (ISD) in RTs across both tasks, measured in milliseconds and with log10 transformation.

Secondary Outcome Measures

  1. Wide Range Achievement Test- 4th Edition (WRAT-4) Reading Recognition Score [Day 1 (Visit 1)]

    WRAT-4 is a brief test of single word reading recognition that provides a proxy of literacy and general intellectual ability. Standard scores for the WRAT-4 subtests range from a low of 55 to a high of 145. The higher the score, the higher the level of literacy and general intellectual ability.

  2. Brief International Cognitive Assessment for MS (BICAMS) Symbol Digit Modalities Test (SDMT) Score [Day 1 (Visit 1)]

    SDMT is 90-second cognitive task in which the participant is shown a sheet containing rows of symbols. Each symbol corresponds to a specific number. The participant's task is to say out loud the number associated with each symbol. SDMT is used as a general cognitive screen to detect severe cognitive impairment. The final score is the correct number of substitutions in 90 seconds, scores range between 0 and 110. The lower the score, the more severe the cognitive impairment.

  3. BICAMS Rey Auditory Verbal Learning Test (RAVLT) Score [Day 1 (Visit 1)]

    RAVLT is a well-recognized measure of a person's ability to encode, combine, store and recover verbal information in different stages of immediate memory. consists of presenting a list of 15 words across consecutive trials. The list is read aloud to the participant, and then the participant is immediately asked to recall as many words as one remembers. This procedure is repeated for 5 consecutive trials (Trials 1 to 5). The total score is the sum of trials 1-5 and ranges from 0-75. The lower the score, the more severe the cognitive impairment.

  4. BICAMS Brief Visuospatial Memory Test Revised (BVMT-R) Score [Day 1 (Visit 1)]

    Visual/spatial memory is assessed in BICAMS using the BVMT-R. In this test, six abstract designs are presented for 10 sec. The display is removed from view and patients render the stimuli via pencil on paper manual responses. Each design receives from 0 to 2 points representing accuracy and location. There are three Learning Trials, and the score is reported as the total number of points earned over the trials. Thus, scores range from 0 to 12 per trial; total score range is 0 to 36 for all three trials. The lower the score, the more severe the cognitive impairment.

Eligibility Criteria


Ages Eligible for Study:
23 Years to 59 Years
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Inclusion Criteria:
  • Ages 23-59 years old (inclusive)

  • Prodromal MS (defined by radiologically isolated syndrome ≤ 6 months from first MRI or clinically isolated syndrome ≤ 3 months from first clinical event)

Exclusion Criteria:
  • Below average estimated premorbid cognitive functioning (based on WRAT-4 reading recognition standard z-score < 85).

  • Presence of severe cognitive impairment (based on SDMT age normative z-score <-3.0).

  • Primary psychiatric disorder that would influence ability to participate.

  • Current uncontrolled seizure disorder.

  • Current substance abuse disorder.

  • History of head trauma in the past year (e.g., head injury, brain surgery) or medical device implanted in the head (such as Deep Brain Stimulator) or in the neck (such as a Vagus Nerve Stimulator).

  • Pregnant or breastfeeding

Additional Exclusion Criteria for tDCS-MRI Participants

  • Extreme claustrophobia

  • Any skin disorder/sensitive skin (e.g., eczema, severe rashes), blisters, open wounds, burn including sunburns, cuts or irritation, or other skin defects which compromise the integrity of the skin at or near stimulation locations (where electrodes are placed)

  • Treatment for a communicable skin disorder currently or over the past 12 months

  • Have any irremovable piercings, metallic based-tattoos, or MRI-contraindicated implants (e.g. pacemakers and defibrillators)

Contacts and Locations


Site City State Country Postal Code
1 NYU Langone Health New York New York United States 10016

Sponsors and Collaborators

  • NYU Langone Health
  • National Multiple Sclerosis Society


  • Principal Investigator: Leigh Charvet, MD, NYU Langone Health

Study Documents (Full-Text)

None provided.

More Information


None provided.
Responsible Party:
NYU Langone Health Identifier:
Other Study ID Numbers:
  • 21-01385
First Posted:
Sep 16, 2022
Last Update Posted:
Sep 16, 2022
Last Verified:
Sep 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:
Studies a U.S. FDA-regulated Drug Product:
Studies a U.S. FDA-regulated Device Product:
Product Manufactured in and Exported from the U.S.:
Additional relevant MeSH terms:

Study Results

No Results Posted as of Sep 16, 2022