search
Back to results

Cognitive Markers in Prodromal MS

Primary Purpose

Multiple Sclerosis

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Active tDCS
Sponsored by
NYU Langone Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional screening trial for Multiple Sclerosis

Eligibility Criteria

23 Years - 59 Years (Adult)All SexesDoes not accept 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)

Sites / Locations

  • NYU Langone HealthRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Group with tDCS-MRI

Group without tDCS- MRI

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Cerebral metabolic rate of oxygen (CMRO2)
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.
Intra-Individual Variability (IIV) as measured by Cogstate Brief Battery (CBB)
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

Wide Range Achievement Test- 4th Edition (WRAT-4) Reading Recognition Score
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.
Brief International Cognitive Assessment for MS (BICAMS) Symbol Digit Modalities Test (SDMT) Score
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.
BICAMS Rey Auditory Verbal Learning Test (RAVLT) Score
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.
BICAMS Brief Visuospatial Memory Test Revised (BVMT-R) Score
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.

Full Information

First Posted
September 13, 2022
Last Updated
February 1, 2023
Sponsor
NYU Langone Health
Collaborators
National Multiple Sclerosis Society
search

1. Study Identification

Unique Protocol Identification Number
NCT05543915
Brief Title
Cognitive Markers in Prodromal MS
Official Title
Intra-Individual Variability in Cognitive Performance as a Marker of Prodromal Disability in MS
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 18, 2022 (Actual)
Primary Completion Date
June 18, 2024 (Anticipated)
Study Completion Date
June 18, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
Collaborators
National Multiple Sclerosis Society

4. Oversight

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

5. 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.
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 (ClinicalTrials.gov Identifier: NCT03564496, IRB i18-00548) using simultaneous transcranial direct current stimulation (tDCS) during the imaging acquisition.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis

7. Study Design

Primary Purpose
Screening
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group with tDCS-MRI
Arm Type
Experimental
Arm Description
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.
Arm Title
Group without tDCS- MRI
Arm Type
No Intervention
Arm Description
Participants will have include a cognitive assessment and an optional gait assessment
Intervention Type
Device
Intervention Name(s)
Active tDCS
Intervention Description
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.
Primary Outcome Measure Information:
Title
Cerebral metabolic rate of oxygen (CMRO2)
Description
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.
Time Frame
4 minutes
Title
Intra-Individual Variability (IIV) as measured by Cogstate Brief Battery (CBB)
Description
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.
Time Frame
Day 1 (Visit 1)
Secondary Outcome Measure Information:
Title
Wide Range Achievement Test- 4th Edition (WRAT-4) Reading Recognition Score
Description
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.
Time Frame
Day 1 (Visit 1)
Title
Brief International Cognitive Assessment for MS (BICAMS) Symbol Digit Modalities Test (SDMT) Score
Description
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.
Time Frame
Day 1 (Visit 1)
Title
BICAMS Rey Auditory Verbal Learning Test (RAVLT) Score
Description
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.
Time Frame
Day 1 (Visit 1)
Title
BICAMS Brief Visuospatial Memory Test Revised (BVMT-R) Score
Description
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.
Time Frame
Day 1 (Visit 1)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
23 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Luis Fernandez
Phone
929-455-5090
Email
Luis.Fernandez2@nyulnagone.org
First Name & Middle Initial & Last Name or Official Title & Degree
Matthew Lustberg
Email
matthew.luistberg@nyulangone.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leigh Charvet, MD
Organizational Affiliation
NYU Langone Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luis Fernandez
Phone
929-455-5090
Email
Luis.Fernandez2@nyulnagone.org
First Name & Middle Initial & Last Name & Degree
Matthew Lustberg
Email
matthew.lustberg@nyulangone.org
First Name & Middle Initial & Last Name & Degree
Leigh Charvet, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Cognitive Markers in Prodromal MS

We'll reach out to this number within 24 hrs