Trial Outcomes & Findings for Cognitive Markers in Prodromal MS (NCT NCT05543915)

Last Updated: 2025-07-14

Results Overview

CMRO2 is the amount of O2 the brain consumes per unit of time (in μmol O2/100g tissue per minute). 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.

Recruitment status

COMPLETED

Study phase

Target enrollment

60 participants

Primary outcome timeframe

Day 1 (Visit 1 - approximately 4 minutes)

Results posted on

2025-07-14

Participant Flow

Participant milestones

Participant milestones
Measure	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. 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.	Group Without tDCS- MRI Participants will have include a cognitive assessment and an optional gait assessment
Overall Study STARTED	30	30
Overall Study COMPLETED	30	29
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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. 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.	Group Without tDCS- MRI Participants will have include a cognitive assessment and an optional gait assessment
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Cognitive Markers in Prodromal MS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group With tDCS-MRI n=30 Participants 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. 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.	Group Without tDCS- MRI n=29 Participants Participants will have include a cognitive assessment and an optional gait assessment	Total n=59 Participants Total of all reporting groups
Age, Continuous	34 years STANDARD_DEVIATION 8.3 • n=5 Participants	37 years STANDARD_DEVIATION 8.7 • n=7 Participants	36 years STANDARD_DEVIATION 8.8 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	23 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	19 Participants n=5 Participants	3 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	19 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	4 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	16 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants	29 participants n=7 Participants	59 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 (Visit 1 - approximately 4 minutes)

Population: Note - assessed in the "Group with tDCS-MRI" arm only.

Outcome measures

Outcome measures
Measure	Group With tDCS-MRI n=29 Participants 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. 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.	Group Without tDCS- MRI Participants will have include a cognitive assessment and an optional gait assessment
Cerebral Metabolic Rate of Oxygen (CMRO2)	8.17 micro-mol/100g/min Standard Deviation 12.99	—

PRIMARY outcome

Timeframe: Day 1 (Visit 1)

The core Cogstate Reaction Time (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.

Outcome measures

Outcome measures
Measure	Group With tDCS-MRI n=30 Participants 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. 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.	Group Without tDCS- MRI n=29 Participants Participants will have include a cognitive assessment and an optional gait assessment
Intra-Individual Variability (IIV) as Measured by Cogstate Brief Battery (CBB)	0.37 log10(ms) Standard Deviation 0.64	0.34 log10(ms) Standard Deviation 0.64

SECONDARY outcome

Timeframe: 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 raw 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. The raw score is converted to a Z-score with a central value of 0. Standard deviations below the mean indicate a worse outcome; a Z-score of -1.5 or lower suggests a significant deviation from the average performance, potentially indicating cognitive impairment.

Outcome measures

Outcome measures
Measure	Group With tDCS-MRI n=30 Participants 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. 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.	Group Without tDCS- MRI n=29 Participants Participants will have include a cognitive assessment and an optional gait assessment
Brief International Cognitive Assessment for MS (BICAMS) Symbol Digit Modalities Test (SDMT) Z-Score	-1.09 Z-score Standard Deviation 1.25	-1.03 Z-score Standard Deviation 1.28

SECONDARY outcome

Timeframe: 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. The raw score is converted to a Z-score with a central value of 0. Standard deviations below the mean indicate a worse outcome; a Z-score of -1.5 or lower indicates impairment, meaning the individual's performance is significantly below the average of their peer group.

Outcome measures

Outcome measures
Measure	Group With tDCS-MRI n=30 Participants 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. 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.	Group Without tDCS- MRI n=29 Participants Participants will have include a cognitive assessment and an optional gait assessment
BICAMS Rey Auditory Verbal Learning Test (RAVLT) Z-Score	-0.17 Z-score Standard Deviation 0.87	-0.25 Z-score Standard Deviation 0.91

SECONDARY outcome

Timeframe: 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. The raw score is converted to a Z-score with a central value of 0. Standard deviations below the mean indicate a worse outcome; a Z-score of -1.5 or lower on the BVMT-R is generally considered indicative of cognitive impairment.

Outcome measures

Outcome measures
Measure	Group With tDCS-MRI n=30 Participants 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. 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.	Group Without tDCS- MRI n=29 Participants Participants will have include a cognitive assessment and an optional gait assessment
BICAMS Brief Visuospatial Memory Test Revised (BVMT-R) Z-Score	0.14 Z-score Standard Deviation 1.33	-0.02 Z-score Standard Deviation 0.85

Adverse Events

Group With tDCS-MRI

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Group Without tDCS- MRI

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Group With tDCS-MRI n=30 participants at risk 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. 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.	Group Without tDCS- MRI n=29 participants at risk Participants will have include a cognitive assessment and an optional gait assessment
Skin and subcutaneous tissue disorders Localized warmth sensation at the electrode site	3.3% 1/30 • 1 day (during baseline session). Participant self-report.	0.00% 0/29 • 1 day (during baseline session). Participant self-report.

Additional Information

Guiseppina Pilloni

NYU Langone Health

Phone: 646-501-9274

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place