Cathodal tDCS in MCI: A Randomized, Double-Blind, Sham-Controlled Pilot Study

Study Overview
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Brief Summary
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This study evaluates the application of non-invasive brain stimulation in the treatment of Mild Cognitive Impairment (MCI) in adults aged 55-85. Half of the participants will receive transcranial direct current stimulation (tDCS), while the other half will receive sham (like placebo) stimulation.

Detailed Description
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The purpose of this study is to investigate whether giving transcranial direct current stimulation (tDCS) treatment using an investigational device called the Soterix tES Device (tDCS device) on the right side of the brain can improve performance on cognitive tests. Investigational means that the tDCS device is not approved by the U.S. Food and Drug Administration (FDA) for the use in this study. tDCS is a non-invasive way to electrically stimulate the brain. The tDCS device is portable and runs on two 9-volt batteries. Electrodes from the tDCS device carry weak electrical current through the scalp and skull and into the brain. When the direction of the electric current flow is called cathodal, the brain under the site of stimulation reduces its activity. When tasks are performed, certain parts of the brain are activated. Research studies have shown that younger adults and older adults activate similar parts of the brain when performing the same task (a memory task, for example). However, other researchers found older adults who scored worse on memory tasks, and those with Mild Cognitive Impairment, activated an additional part of the brain so both sides of the brain are activated. Researchers are not sure whether this additional activation is helpful or not. Investigators in this study believe that this extra activation may be contributing to worse performance on tasks. It may be possible to use tDCS to reduce the brain activity on the extra activation (right) side in older adults, to resemble an activation pattern seen in younger adults (or higher scoring cohort). Using cathodal tDCS to reduce brain activity might help the brain in performing tasks.

Official Title
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Cathodal Transcranial Direct Current Stimulation (tDCS) in Mild Cognitive Impairment (MCI): A Randomized, Double-Blind, Sham-Controlled Pilot Study

Conditions
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Mild Cognitive Impairment, Cognitive Impairment, Neurocognitive Dysfunction

Intervention / Treatment
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* Device: Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female outpatients with confirmed MCI diagnosis Age 55-85 Right handed (tested using the Edinburgh handedness inventory) Total PHQ-8 of ≤ 16 which signifies no severe depression All participants and/or caregivers must be able to provide informed consent Exclusion Criteria: Neurodegenerative disease (e.g. Parkinson's, Huntington's, Multiple Sclerosis) other than MCI Previous brain lesion Intracranial abnormality such as prior stroke History of seizure disorder or epilepsy A true positive response, after patient clarification, to any question on the modified TMS/tDCS Adult Safety Screen questionnaire that would impact patient safety Any history of brain stimulation treatment (e.g., electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), vagal nerve therapy (VNS), deep brain stimulation (DBS)) Use of any investigational drug within 4 weeks Cardiac pacemakers, implanted medication pumps, intracardiac lines; acute or unstable cardiac disease; intracranial implants (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head (exception: mouth/dental work) that cannot be safely removed Known or suspected pregnancy (extremely unlikely as the age range for this study is 55-85 years)

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized 1:1 to active or sham transcranial direct current stimulation (tDCS) intervention
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active tDCS<br>Active tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The active tDCS intervention include stimulation for 15 minutes at 1mA. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week. | Device: Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001<br>* Transcranial direct current stimulation works by sending constant, low direct current through the electrodes. When these electrodes are placed in the region of interest, the current induces intracerebral current flow. This current flow then either increases or decreases the neuronal excitability in the specific area being stimulated based on which type of stimulation is being used. This change of neuronal excitability leads to alteration of brain function, which can be used in various therapies as well as to provide more information about the functioning of the human brain.<br>* Other names: Cathodal tDCS;|
| Sham Comparator: Sham tDCS<br>Sham tDCS uses the Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001. The sham tDCS intervention lasts for 15 minutes. The cathode electrode will be placed over the right dorsolateral prefrontal cortex with reference electrode (anode) over the left dorsolateral prefrontal cortex. Both electrodes are covered by saline-soaked sponges that are held against the scalp by a pair of large, adjustable head straps. Treatment sessions will last for 15 minutes. 5 consecutive treatment sessions will be completed within 1 week. | Device: Soterix Medical 1x1 Low Intensity Transcranial Electrical Stimulator (tES) Model 2001<br>* Transcranial direct current stimulation works by sending constant, low direct current through the electrodes. When these electrodes are placed in the region of interest, the current induces intracerebral current flow. This current flow then either increases or decreases the neuronal excitability in the specific area being stimulated based on which type of stimulation is being used. This change of neuronal excitability leads to alteration of brain function, which can be used in various therapies as well as to provide more information about the functioning of the human brain.<br>* Other names: Cathodal tDCS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Flanker Inhibitory Control and Attention Test Scores | Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10. | Baseline, 1-month post intervention | 
| Change in Picture Vocabulary Test Scores | Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10. | Baseline, 1 month post intervention | 
| Change in List Sorting Working Memory Test Scores | Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10. | Baseline, 1 month post intervention | 
| Change in Dimensional Change Card Sort Test | Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10. | Baseline, 1 month post intervention | 
| Change in Pattern Comparison Processing Speed Test Scores | Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10. | Baseline, 1 month post intervention | 
| Change in Picture Sequence Memory Test v2.1 Score | Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10. | Baseline, 1 month post intervention | 
| Change in Oral Reading Recognition Test Score | Post-intervention score comparison between the intervention and control group measured by the NIH Toolbox Cognition Battery Test. The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10. | Baseline, 1 month post intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mild Cognitive Impairment (MCI), Transcranial Direct Current Stimulation (tDCS)