Assessment of tDCS-Induced Neuronal Responses in Multiple Sclerosis (MS) With Advanced MRI

The objective of this trial is to measure the changes in neural activities during tDCS session using Magnetic Resonance Imaging (MRI). Participants (N=60) (20 Healthy Controls and 40 participants with neurological disorders, ie. multiple sclerosis) will be recruited to complete self-report measures and a brief cognitive assessment and then undergo an hour long stand-alone MRI scan while simultaneously undergoing tDCS stimulation. Methodology for this study is the administration of 15-minutes of of active tDCS during MRI acquisition compared to time without active tDCS.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Device: tDCS Administration during MRI; Device: Remotely-supervised Daily tDCS Administration; Device: Optional 15 minutes of imaging + simultaneous tDCS up to 4.0mA

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for MS Patients:

• Participants must be 18 years of age or older
• Standardized SDMT Z-score > - 3.0
• Fatigue Severity Scale score > 36
• Definite MS diagnosis as assessed by licensed physician any subtype including Relapsing Remitting (RRMS), Primary Progressive (PPMS) or Secondary Progressive (SPMS)
• Score of ≤ 7.0 on the Expanded Disability Status Scale
• Clinically stable without disease progression in the past 3 months
• Has stable and continuous access to internet service at home compatible with the study laptop (Wi-Fi or Ethernet cable)
• Adequate internet capacity for remote monitoring, as tested by http://www.speedtest.net/
• Adequate home facilities (enough space, access to quiet and distraction free area)
• Able to commit to the four-week period of training sessions with baseline and two follow-up visits

Exclusion Criteria for MS Patients:

• Extreme claustrophobia
• Relapse or steroid use in previous month
• History of mental retardation, pervasive developmental disorder, or other neurological condition associated with cognitive impairment
• Primary psychiatric disorder that would influence ability to participate
• Current uncontrolled seizure disorder
• Current substance abuse disorder
• 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, MRI-contraindicated implantations or metallic based-tattoos
• Pregnant or breastfeeding
• Wide Range Achievement Test-4th Edition (WRAT-4) Reading Recognition Scaled Score < 85
• Beck Depression Inventory - Fast Screen (BDI-FS) score > 9

Inclusion Criteria for Healthy Controls:

• Participants must be 18 years of age or older
• Standardized SDMT Z-score > - 3.0
• Have not been diagnosed with MS or other neurological disorder
• Adequate internet capacity for remote monitoring, as tested by http://www.speedtest.net/ (HC subgroup only)
• Adequate home facilities including enough space, access to quiet and distraction free area (HC subgroup only)
• Able to commit to the four-week period of training sessions with baseline and one follow-up visit (HC subgroup only)

Exclusion Criteria for Healthy Controls:

• Extreme claustrophobia
• History of mental retardation, pervasive developmental disorder or other neurological condition associated with cognitive impairment
• Primary psychiatric disorder that would influence ability to participate
• Current uncontrolled seizure disorder
• Current substance abuse disorder
• 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, MRI-contraindicated implantations or metallic based-tattoos
• Pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy Controls; Healthy Controls will be given approximately 15 minutes of active tDCS during MRI during the initial visit.	Device: tDCS Administration during MRI; All participants including healthy controls and MS patients will be given approximately 15 minutes of active tDCS during MRI. The simultaneous tDCS will be performed up to 2 mA dose intensity to determine CMRO2 changes from when the tDCS is on to when the tDCS is off. The stimulation consists of 15-min up to 2 mA tDCS using 5x5 cm electrode sponges with ~30s ramp-up and ramp-down periods.
Experimental: MS Patients; MS patients will be given approximately 15 minutes of active tDCS during MRI during the initial visit. After the first MRI visit, MS patients will receive remotely-supervised home tDCS treatment for a month to test the cumulative effects of tDCS. Participants will complete 20 x 2.0mA x 20 minute tDCS sessions paired with cognitive training over 4-week period (20 mins per day and weekend off) with electrodes placed to target the bilateral DLPFC. Around 3 months after the 20-session treatment, MS patients only will be asked to come to the clinic for neuropsychological assessments.	Device: tDCS Administration during MRI; All participants including healthy controls and MS patients will be given approximately 15 minutes of active tDCS during MRI. The simultaneous tDCS will be performed up to 2 mA dose intensity to determine CMRO2 changes from when the tDCS is on to when the tDCS is off. The stimulation consists of 15-min up to 2 mA tDCS using 5x5 cm electrode sponges with ~30s ramp-up and ramp-down periods.; Device: Remotely-supervised Daily tDCS Administration; While the first tDCS session will be performed at clinic under the full supervision, remaining sessions 2-20 (~ 1 month) will be completed at home with remote monitoring by the study technician. Participants in the HC subgroup who opt-in to the additional 15 minutes of imaging +tDCS may complete the first session remotely. For at-home tDCS administration, participants will be given the specially-designed tDCS device and headset, study laptop computer for secure video monitoring with study technician (must have internet access) and access to the cognitive training program, a detailed reference manual, and a training video. The device will produce up to 2.0 mA stimulation for around 20 minutes, and will not operate without the correct headset placement. The device will also automatically abort the session if optimal conditions are not maintained. It reports and records a completion code for each session.
Active Comparator: Healthy Control subgroup; The Healthy Control subgroup will be given approximately 15 minutes of active tDCS during MRI during the initial visit. Participants in the healthy control subgroup will be given the option to have an additional 15 minutes of brain imaging, which will include 10 minutes of simultaneous tDCS at up to 4.0mA, added to the end of their baseline scan. After the first MRI visit, HC subgroup patients will receive remotely-supervised home tDCS treatment for a month to test the cumulative effects of tDCS. Participants will complete 20 x 2.0mA x 20 minute tDCS sessions paired with cognitive training over 4-week period (20 mins per day and weekend off) with electrodes placed to target the bilateral DLPFC.	Device: tDCS Administration during MRI; All participants including healthy controls and MS patients will be given approximately 15 minutes of active tDCS during MRI. The simultaneous tDCS will be performed up to 2 mA dose intensity to determine CMRO2 changes from when the tDCS is on to when the tDCS is off. The stimulation consists of 15-min up to 2 mA tDCS using 5x5 cm electrode sponges with ~30s ramp-up and ramp-down periods.; Device: Remotely-supervised Daily tDCS Administration; While the first tDCS session will be performed at clinic under the full supervision, remaining sessions 2-20 (~ 1 month) will be completed at home with remote monitoring by the study technician. Participants in the HC subgroup who opt-in to the additional 15 minutes of imaging +tDCS may complete the first session remotely. For at-home tDCS administration, participants will be given the specially-designed tDCS device and headset, study laptop computer for secure video monitoring with study technician (must have internet access) and access to the cognitive training program, a detailed reference manual, and a training video. The device will produce up to 2.0 mA stimulation for around 20 minutes, and will not operate without the correct headset placement. The device will also automatically abort the session if optimal conditions are not maintained. It reports and records a completion code for each session.; Device: Optional 15 minutes of imaging + simultaneous tDCS up to 4.0mA; Participants in the healthy control subgroup who are willing may have an additional 15 minutes of imaging combined with 10 minutes of simultaneous tDCS of up to 4.0mA added at the end of their baseline scan. In this case, after the initial imaging and tDCS portion is complete, the participant will remain on the scanner for an additional 15 minutes during which brain imaging will continue and will be combined with 10 minutes of simultaneous tDCS up to 4.0mA. This will be a one-time add-on and will not be required at follow-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral Metabolic Rate of Oxygen (CMRO2)	Measured via MRI. CMRO2 is the amount of O2 the brain consumes per unit of time (in μmol O2/100g tissue per minute)	Baseline Visit
Cerebral Metabolic Rate of Oxygen (CMRO2)	Measured via MRI. CMRO2 is the amount of O2 the brain consumes per unit of time (in μmol O2/100g tissue per minute)	Intermediate Visit (Month 1)
Neuronal Reactivity (NR)	NR represents tDCS-induced global neural reactivity measured by CMRO2 levels in cells available to respond to neural stimuli. NR is measured as the percentage change of CMRO2 from no tDCS to real tDCS. tDCS will be administered in one visit and will last for approximately 15 minutes.	Baseline Visit (pre-tDCS, post-tDCS)
Neuronal Reactivity (NR)	NR represents tDCS-induced global neural reactivity measured by CMRO2 levels in cells available to respond to neural stimuli. NR is measured as the percentage change of CMRO2 from no tDCS to real tDCS.	Baseline, Intermediate Visit (Month 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life in Neurological Disorders (Neuro-QOL) Score	36-item assessment of quality of life measures in participants with neurological disorders. This questionnaire will be administered to MS patients only. The raw score is the sum of responses; this score is transformed to a standardized T-score with a mean of 50 and SD of 10. A T-score of 60 indicates worse (undesirable) self-reported health.	Baseline Visit
Quality of Life in Neurological Disorders (Neuro-QOL) Score	36-item assessment of quality of life measures in participants with neurological disorders. This questionnaire will be administered to MS patients only. The raw score is the sum of responses; this score is transformed to a standardized T-score with a mean of 50 and SD of 10. A T-score of 60 indicates worse (undesirable) self-reported health.	Intermediate Visit (Month 1)
Quality of Life in Neurological Disorders (Neuro-QOL) Score	36-item assessment of quality of life measures in participants with neurological disorders. This questionnaire will be administered to MS patients only. The raw score is the sum of responses; this score is transformed to a standardized T-score with a mean of 50 and SD of 10. A T-score of 60 indicates worse (undesirable) self-reported health.	Final Visit (Month 4)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2018
• Primary Completion (Actual): September 29, 2021
• Study Completion (Actual): September 29, 2021

Study Registration Dates

• First Submitted: June 11, 2018
• First Submitted That Met QC Criteria: June 11, 2018
• First Posted (Actual): June 20, 2018

Study Record Updates

• Last Update Posted (Actual): January 17, 2024
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Anodal transcranial stimulation (tDCS)
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: 18-00548

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data collection will be for pilot data and exploratory analysis.

Drug and device information, study documents

• 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.: No