Multiple Sclerosis
Conditions
Keywords
Anodal transcranial stimulation (tDCS)
Brief summary
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.
Interventions
DEVICEtDCS 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.
DEVICERemotely-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.
DEVICEOptional 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.
Sponsors
NYU Langone Health
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cerebral Metabolic Rate of Oxygen (CMRO2) | Baseline Visit | Measured via MRI. CMRO2 is the amount of O2 the brain consumes per unit of time (in μmol O2/100g tissue per minute) |
| Neuronal Reactivity (NR) | Baseline Visit (pre-tDCS, post-tDCS) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life in Neurological Disorders (Neuro-QOL) Score | Baseline Visit | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Controls Healthy Controls will be given approximately 15 minutes of active tDCS during MRI during the initial visit. | 26 |
| 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. | 36 |
| 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. | 6 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Screen failure | 0 | 3 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Healthy Controls | Total | Healthy Control Subgroup | MS Patients |
|---|---|---|---|---|
| Age, Continuous | 36 years STANDARD_DEVIATION 15.8 | 39.6 years STANDARD_DEVIATION 15 | 36 years STANDARD_DEVIATION 14.54 | 47 years STANDARD_DEVIATION 14.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 60 Participants | 5 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 7 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 11 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 12 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) White | 10 Participants | 38 Participants | 5 Participants | 23 Participants |
| Region of Enrollment United States | 26 Participants | 68 Participants | 6 Participants | 36 Participants |
| Sex: Female, Male Female | 15 Participants | 41 Participants | 3 Participants | 23 Participants |
| Sex: Female, Male Male | 11 Participants | 27 Participants | 3 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 36 | 0 / 6 |
| other Total, other adverse events | 20 / 26 | 27 / 36 | 0 / 6 |
| serious Total, serious adverse events | 0 / 26 | 0 / 36 | 0 / 6 |
Outcome results
Primary
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)
Time frame: Baseline Visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Controls | Cerebral Metabolic Rate of Oxygen (CMRO2) | 165.84 µmol/100g/min | Standard Deviation 25.32 |
| MS Patients | Cerebral Metabolic Rate of Oxygen (CMRO2) | 128.3 µmol/100g/min | Standard Deviation 14 |
| Healthy Control Subgroup | Cerebral Metabolic Rate of Oxygen (CMRO2) | 159.4 µmol/100g/min | Standard Deviation 21.8 |
Primary
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)
Time frame: Intermediate Visit (Month 1)
Population: Only the Healthy Control subgroup and MS patients were evaluated for this outcome measure. The Healthy Control group was not evaluated because they did not receive any additional sessions after the first visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Controls | Cerebral Metabolic Rate of Oxygen (CMRO2) | 146.42 µmol/100g/min | Standard Deviation 27.71 |
| MS Patients | Cerebral Metabolic Rate of Oxygen (CMRO2) | 140.59 µmol/100g/min | Standard Deviation 13.83 |
Primary
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.
Time frame: Baseline Visit (pre-tDCS, post-tDCS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Controls | Neuronal Reactivity (NR) | 9.84 percentage change of CMRO2 | Standard Deviation 10.8 |
| MS Patients | Neuronal Reactivity (NR) | 12.45 percentage change of CMRO2 | Standard Deviation 13.8 |
| Healthy Control Subgroup | Neuronal Reactivity (NR) | 15.61 percentage change of CMRO2 | Standard Deviation 4.69 |
Primary
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.
Time frame: Baseline, Intermediate Visit (Month 1)
Population: Only the Healthy Control subgroup and MS patients were evaluated for this outcome measure. The Healthy Control group was not evaluated because they did not receive any additional sessions after the first visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Controls | Neuronal Reactivity (NR) | 4.32 percentage change of CMRO2 | Standard Deviation 8.44 |
| MS Patients | Neuronal Reactivity (NR) | 22.5 percentage change of CMRO2 | Standard Deviation 6.88 |
Secondary
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.
Time frame: Baseline Visit
Population: Only MS patients were evaluated for this outcome measure. The Healthy Control group and Health Control subgroup were not administered the Neuro-QOL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Controls | Quality of Life in Neurological Disorders (Neuro-QOL) Score | 50.81 T-score | Standard Deviation 13.04 |
Secondary
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.
Time frame: Intermediate Visit (Month 1)
Population: Only MS patients were evaluated for this outcome measure. The Healthy Control group and Health Control subgroup were not administered the Neuro-QOL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Controls | Quality of Life in Neurological Disorders (Neuro-QOL) Score | 36.38 T-score | Standard Deviation 13.16 |
Secondary
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.
Time frame: Final Visit (Month 4)
Population: Only MS patients were evaluated for this outcome measure. The Healthy Control group and Health Control subgroup were not administered the Neuro-QOL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Controls | Quality of Life in Neurological Disorders (Neuro-QOL) Score | 39.12 T-score | Standard Deviation 12.65 |