Treatment of Cognitive Deficits in Multiple Sclerosis With High-Definition Transcranial Direct Current Stimulation

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

— MS-HDtDCS  

Official title:

Treatment of Cognitive Deficits in Multiple Sclerosis With High-Definition Transcranial Direct Current Stimulation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05958381
• Other study ID #: 23-521
• Secondary ID: HT94252310618E04
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 18, 2023
• Est. completion date: June 30, 2027

Study information

• Verified date: January 2024
• Source: The University of Texas at Dallas
• Contact: Ashna Adhikari, MS
• Phone: 972-833-3161
• Email: Ashna.Adhikari[@]UTDallas.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to test whether low level electric stimulation, called transcranial Direct Current Stimulation (tDCS), on the part of the brain (i.e., presupplementary motor area) thought to aid in memory will improve verbal retrieval in multiple sclerosis patients. The primary outcome measures are neuropsychological assessments of verbal retrieval, and the secondary measures are neuropsychological assessments of other cognitive abilities and electroencephalography (EEG) measures. Additionally, the study will examine the degree to which baseline assessments of cognition and concussion history predict responses to treatment over time, both on assessments administered within the intervention period and at follow-up.

Description:

Using two treatment arms, the study will examine improvement of verbal retrieval and other cognitive deficits associated with multiple sclerosis by comparing (1) 1 milliamp transcranial direct current stimulation (tDCS) active treatment applied to presupplementary motor area for 20 minutes over 10 sessions to (2) sham tDCS following the same schedule. Additionally, after completing the initial active or sham treatment and immediate and 2-month follow-up testing sessions, selected participants will be invited back for newly assigned treatment conditions, 20 minutes over 10 sessions and will be re-evaluated at immediate and 2-month follow-up testing sessions.

Patients with multiple sclerosis and observed cognitive deficits will be randomly assigned to one of the two treatment arms (and re-assigned for the second round of intervention, as described above). Primary outcome verbal retrieval measures, secondary neuropsychological and electroencephalography (EEG) measures, and prescreening assessments for study concussion history and contraindications for treatment will be collected prior to being assigned to a treatment arm (i.e., baseline).

Primary outcome verbal retrieval measures and secondary neuropsychological and electroencephalography (EEG) measures will be at baseline and two times following treatment competition (i.e., immediate and 2-months). For participants selected for the second round of intervention, primary outcome verbal memory measures and secondary neuropsychological and electroencephalography (EEG) measures will be collected again two times immediately following completion of the last treatment and 2-months afterward.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: June 30, 2027
• Est. primary completion date: June 29, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

º Diagnosed with relapsing-remitting multiple sclerosis (RRMS)

º Memory retrieval deficit based on neuropsychological testing done in our lab

º Must be fluent in speaking and reading English.

Exclusion Criteria:

º Relapse or acute MS exacerbation or a course of steroids in the two months preceding the testing

º Participants using benzodiazepines must have been on a stable dose for at least two months

º Potentially confounding psychological or neurological disorder, including:

• dementia of any type

• epilepsy or other seizure disorders

• severe traumatic brain injury

• brain tumor

• present drug abuse

• stroke

• blood vessel abnormalities in the brain

• Parkinson's disease

• Huntington's disease

º inability to give informed consent

º cranial implants

º skull defects that affect tDCS administration

º use of medications that interact with or potentially interact with tDCS effects, including:

• anti-convulsants

• L-dopa

• carbamazepine

• sulpiride

• pergolide

• lorazepam

• rivastigmine

• dextromethorphan

• D-cycloserine

• flunarizine

• ropinirole

• citalopram

• stimulants (dextroamphetamine/amphetamine/modafinil/armodafinil) must be stopped during enrollment

Related Conditions & MeSH terms

• Cognition Disorders
• Cognitive Dysfunction
• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Device:
• Transcranial Direct Current Stimulation
Transcranial direct current stimulation will be delivered via a Neuroelectrics Starstim tES. Stimulation will consist of 1 milliamp stimulation, with anodal stimulation delivered at electrode Fz (International 10/10 System for electroencephalography electrode placement) and electrodes F7, FP1, FP2, and F8 as returns. All electrodes are 1 cm diameter Ag/AgCl electrodes and make contact with the scalp via connective gel. Stimulation will linearly ramp up from 0 milliamps to 1 milliamp over 60 seconds, then remain at 1 milliamp of stimulation over 20 minutes, and finally ramping down at to 0 milliamps over 60 seconds.
• Sham transcranial direct current stimulation
Sham transcranial direct current stimulation will be delivered via a Neuroelectrics Starstim tES. The sham setup will consist of anodal electrode Fz (International 10/10 System for electroencephalography electrode placement) and electrodes F7, FP1, FP2, and F8 as returns. All electrodes are 1 cm diameter Ag/AgCl electrodes and make contact with the scalp via connective gel. Stimulation will linearly ramp up from 0 milliamps to 1 milliamp over 60 seconds, ramp down to 0 milliamps over 60 seconds and then be left off for 20 minutes.

Locations

Country	Name	City	State
United States	The University of Texas at Dallas	Richardson	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas at Dallas	University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment group differences in change from Baseline to 1-week Post-Treatment on Category Fluency	Evaluation of treatment group differences in change on Category Fluency from baseline to 1-week post-treatment.; Metric: Number of Correct Items Generated	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 1-week Post-Treatment
Primary	Treatment group differences in change from Baseline to 2-months Post-Treatment on Category Fluency	Evaluation of treatment group differences in change on Category Fluency from baseline to 2-months post-treatment.; Metric: Number of Correct Items Generated	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-month Post-Treatment
Primary	Treatment group differences in change from Baseline to 1-week Post-Treatment on COWAT	Evaluation of treatment group differences in change on COWAT from baseline to 1-week post-treatment.; Metric: Number of Correct Items Generated	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 1-week Post-Treatment
Primary	Treatment group differences in change from Baseline to 2-months Post-Treatment on COWAT	Evaluation of treatment group differences in change on COWAT from baseline to 2-months post-treatment.; Metric: Number of Correct Items Generated	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-months Post-Treatment
Secondary	Treatment group differences in change from Baseline to 1-week Post-Treatment on the Trail Making Test (Part A)	Evaluation of treatment group differences in change on the Trail Making Test (Part A) from baseline to 1-week post-treatment.; Metric: Time to Solution	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 1-week Post-Treatment
Secondary	Treatment group differences in change from Baseline to 1-week Post-Treatment on the Trail Making Test (Part B)	Evaluation of treatment group differences in change on the Trail Making Test (Part B) from baseline to 1-week post-treatment.; Metric: Time to Solution	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 1-week Post-Treatment
Secondary	Treatment group differences in change from Baseline to 1-week Post-Treatment on the Delis Kaplan Color Word Interference Test	Evaluation of treatment group differences in change on the Delis Kaplan Color Word Interference Test from baseline to 1-week post-treatment.; Metric: Time to Name Items	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 1-week Post-Treatment
Secondary	Treatment group differences in change from Baseline to 1-week Post-Treatment on on the Digit Span Forward	Evaluation of treatment group differences in change on the on the Digit Span Forward from baseline to 1-week post treatment.; Metric: Memory Span	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 1-week Post-Treatment
Secondary	Treatment group differences in change from Baseline to 1-week Post-Treatment on the Digit Span Backward	Evaluation of treatment group differences in change on the Digit Span Backward from baseline to 1-week post treatment.; Metric: Memory Span	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 1-week Post-Treatment
Secondary	Treatment group differences in change from Baseline to 1-week Post-Treatment on on the the Rey-Osterrieth Complex Figure Test	Evaluation of treatment group differences in change on the Rey-Osterrieth Complex Figure Test from baseline to 1-week post treatment.; Metric: Score	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 1-week Post-Treatment
Secondary	Treatment group differences in change from Baseline to 1-week Post-Treatment on the Digit Symbol Substitution Test	Evaluation of treatment group differences in change on the on the the Digit Symbol Substitution Test from baseline to 1-week post treatment.; Metric: Number of Items	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 1-week Post-Treatment
Secondary	Treatment group differences in change from Baseline to 1-week Post-Treatment on the Grooved Pegboard Test	Evaluation of treatment group differences in change on the Grooved Pegboard Test from baseline to 1-week post-treatment.; Metric: Completion Time	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 1-week Post-Treatment
Secondary	Treatment group differences in change from Baseline to 1-week Post-Treatment on the Semantic Object Retrieval Test	Evaluation of treatment group differences in change on the Semantic Object Retrieval Test from baseline to 1-week post-treatment.; Metric: Number of Correct Names Retrieved	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 1-week Post-Treatment
Secondary	Treatment group differences in change from Baseline to 1-week Post-Treatment on the Boston Naming Test	Evaluation of treatment group differences in change on the Boston Naming Test from baseline to 1-week post-treatment.; Metric: Number of Items Correctly Named	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 1-week Post-Treatment
Secondary	Treatment group differences in change from Baseline to 1-week Post-Treatment on the Auditory Verbal Learning Test	Evaluation of treatment group differences in change on the Auditory Verbal Learning Test from baseline to 1-week post-treatment.; Metric: Number of Items Remembered	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 1-week Post-Treatment
Secondary	Treatment group differences in change from Baseline to 2-months Post-Treatment on the Trail Making Test (Part A)	Evaluation of treatment group differences in change on the Trail Making Test (Part A) from baseline to 2-months post-treatment.; Metric: Time to Solution	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-months Post-Treatment
Secondary	Treatment group differences in change from Baseline to 2-months Post-Treatment on the Trail Making Test (Part B)	Evaluation of treatment group differences in change on the Trail Making Test (Part B) from baseline to 2-months post-treatment.; Metric: Time to Solution	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-months Post-Treatment
Secondary	Treatment group differences in change from Baseline to 2-months Post-Treatment on the Delis Kaplan Color Word Interference Test	Evaluation of treatment group differences in change on the Delis Kaplan Color Word Interference Test from baseline to 2-months post-treatment.; Metric: Time to Name Items	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-months Post-Treatment
Secondary	Treatment group differences in change from Baseline to 2-months Post-Treatment on the Digit Span Forward	Evaluation of treatment group differences in change on the on the Digit Span Forward from baseline to 2-months post-treatment.; Metric: Memory Span	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-months Post-Treatment
Secondary	Treatment group differences in change from Baseline to 2-months Post-Treatment on the Digit Span Backward	Evaluation of treatment group differences in change on the on the Digit Span Backward from baseline to 2-months post-treatment.; Metric: Memory Span	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-months Post-Treatment
Secondary	Treatment group differences in change from Baseline to 2-months Post-Treatment on the Rey-Osterrieth Complex Figure Test	Evaluation of treatment group differences in change on the on the Rey-Osterrieth Complex Figure Test from baseline to 2-months post-treatment.; Metric: Score	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-months Post-Treatment
Secondary	Treatment group differences in change from Baseline to 2-months Post-Treatment on the Digit Symbol Substitution Test	Evaluation of treatment group differences in change on the on the the Digit Symbol Substitution Test from baseline to 2-months post treatment.; Metric: Number of Items	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-months Post-Treatment
Secondary	Treatment group differences in change from Baseline to 2-months Post-Treatment on the Grooved Pegboard Test	Evaluation of treatment group differences in change on the Grooved Pegboard Test from baseline to 2-months post-treatment.; Metric: Completion Time	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-months Post-Treatment
Secondary	Treatment group differences in change from Baseline to 2-months Post-Treatment on the Semantic Object Retrieval Test	Evaluation of treatment group differences in change on the Semantic Object Retrieval Test from baseline to 2-months post-treatment.; Metric: Number of Correct Names Retrieved	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-months Post-Treatment
Secondary	Treatment group differences in change from Baseline to 2-months Post-Treatment on the Boston Naming Test	Evaluation of treatment group differences in change on the Boston Naming Test from baseline to 2-months post-treatment.; Metric: Number of Items Correctly Named	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-months Post-Treatment
Secondary	Treatment group differences in change from Baseline to 2-months Post-Treatment on the Auditory Verbal Learning Test	Evaluation of treatment group differences in change on the Auditory Verbal Learning Test from baseline to 2-months post-treatment.; Metric: Number of Items Remembered	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-months Post-Treatment
Secondary	Treatment group differences in change from Baseline to 1-week Post-Treatment on the Semantic Inhibition Task EEG spectral power	Evaluation of treatment group differences in change on the Semantic Inhibition Task EEG from baseline to 1-week post-treatment.; Metric: EEG spectral (theta) power	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 2-months Post-Treatment
Secondary	Treatment group differences in change from Baseline to 2-months Post-Treatment on the Semantic Inhibition Task EEG spectral power	Evaluation of treatment group differences in change on the Semantic Inhibition Task EEG from baseline to 2-months post-treatment.; Metric: EEG spectral (theta) power	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-months Post-Treatment
Secondary	Treatment group differences in change from Baseline to 1-week Post-Treatment on the Semantic Inhibition Task EEG Event-Related Potential (N2/P3)	Evaluation of treatment group differences in change on the Semantic Inhibition Task EEG from baseline to 1-week post-treatment.; Metric: EEG N2/P3 event-related potential amplitude	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 1-week Post-Treatment
Secondary	Treatment group differences in change from Baseline to 2-months Post-Treatment on the Semantic Inhibition Task EEG Event-Related Potential (N2/P3)	Evaluation of treatment group differences in change on the Semantic Inhibition Task EEG from baseline to 2-months post-treatment.; Metric: EEG N2/P3 event-related potential amplitude	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-months Post-Treatment
Secondary	Treatment group differences in change from Baseline to 1-week Post-Treatment on the Semantic Object Retrieval EEG spectral power	Evaluation of treatment group differences in change on the Semantic Object Retrieval EEG from baseline to 1-week post-treatment.; Metric: EEG spectral (theta) power	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 1-week Post-Treatment
Secondary	Treatment group differences in change from Baseline to 2-months Post-Treatment on the Semantic Object Retrieval EEG spectral power	Evaluation of treatment group differences in change on the Semantic Object Retrieval EEG from baseline to 2-months post-treatment.; Metric: EEG event-related potential amplitude	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 1-week Post-Treatment
Secondary	Treatment group differences in change from Baseline to 1-week Post-Treatment on the Semantic Object Retrieval EEG event-related potential	Evaluation of treatment group differences in change on the Semantic Object Retrieval EEG from baseline to 1-week post-treatment.; Metric: EEG late-onset (750 ms) event-related potential	Outcome measures will be assessed as change over a period of 6 weeks: Change from baseline to 1-week Post-Treatment
Secondary	Treatment group differences in change from Baseline to 2-months Post-Treatment on the Semantic Object Retrieval EEG event-related potential	Evaluation of treatment group differences in change on the Semantic Object Retrieval EEG from baseline to 2-months post-treatment.; Metric: EEG late-onset (750 ms) event-related potential	Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-months Post-Treatment