Digital Therapeutics Research on Efficiency About Mild Cognitive Impairment Study

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficiency and safety of a digital therapeutics(ET-101) for mild cognitive impairment (MCI). This is a randomized, sham-controlled, assessor-blinded, 12-week parallel study. 100 MCI patients will be randomly assigned to two groups. The control group will be provided with a sham device.

Official Title
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Digital Therapeutics (ET-101) Research on Efficiency and Safety About Mild Cognitive Impairment, Randomized, Sham Device, Assessor-blinded, Multi-center Pivotal Study

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Device: ET-101
* Device: Sham Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 55-85 years old Patients diagnosed with mild cognitive impairment according to Petersen criteria A person with subjective memory complaints Memory degradation of z-score ≤ -1 from the normal range of age, gender, and level of education in the memory area of the CREAD-NP or SNSB battery The functional performance of overall cognitive function and daily life ability is sufficiently preserved. Not dementia MMSE 25 or less Adequate vision and hearing for clinical trial Global CDR 0.5 If approved AD treatment drugs(AChEI, memantine, or both) are being administered, they should be administered at a stable dose for at least 12 weeks prior to randomization. Have an identified trial partner (defined as someone who can assist the subject during the trial and spends at least 8 hours per week with the subject). The test partner must provide informed consent. This partner must also be willing and able to provide follow-up information to the subject during the trial. In the opinion of the investigator, the trial partner should spend sufficient time with the subject on a regular basis to ensure that the trial requirements are met. The permanent study partner does not have to live in the same residence as the subject. For study partners not residing with the subject, the investigator should ensure that the subject can easily contact the study partner while the study partner is not with the subject. If it is uncertain whether a subject's care arrangement is suitable for selection, the investigator should discuss this with the Medical Monitor. The trial partner should participate directly in visits where the clinical evaluation of CDR, EQ-5D, ADCS MCI-ADL are performed. No difficulty in using mobile applications using smartphone A person who owns his/her smartphone A person who can call his/her guardian using smartphone by himself/herself No difficulty in reading and writing Korean Willingness and ability to comply with all aspects of the clinical trial protocol Exclusion Criteria: History of a transient ischemic attack(TIA), stroke, seizure within 12 months Psychiatric symptoms that include; History of diagnosis of psychiatric disorders or symptoms that may interfere with the subject's testing procedure (e.g., psychosis, major depression) Responding yes to item 4 or 5 to suicidal ideation part of C-SSRS or any suicidal behavior within 6 months prior to screening, at screening or at randomization visit, or being hospitalized or treated for suicidal behavior in the past 5 years prior to screening All other clinically significant abnormalities, such as Physical examinations, neurological examinations, and vital signs at screening or baseline that, in the opinion of the investigator, may require additional examination or treatment that may interfere with the study procedure or safety Other medical conditions (e.g., heart, respiratory, gastrointestinal, kidney disease) that are not adequately stable controlled or that, in the investigator's opinion, may affect the safety of the subject or interfere with the evaluation of the trial A known or suspected history of drug or alcohol abuse or dependence within 2 years prior to screening Prohibited concomitant medication Surgery that requires general anesthesia is scheduled during the trial period.If only local anesthesia is required and the surgery is the day case without hospitalization after surgery or if, in the opinion of the investigator, the operation does not interfere with the test procedure and the safety of the subject, they should not be excluded History of any type(online/offline) of cognitive intervention or participation in clinical trial regarding cognitive intervention within 12 months

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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ET-101<br>Treatment group | Device: ET-101<br>* Patients have training sessions twice a day. Each training session takes about 10 25 minutes. Cognitive training programs include meditation, cognitive training, and cognitive testing.<br>|
| Sham Comparator: Sham Device<br>Sham group | Device: Sham Device<br>* Sham device has only cognitive function test excluding training programs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with the same or reduced ADAS-cog14 score | The 14 items of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog14): Total scores range from 0 to 90, with higher scores indicating more worsening. Compare the proportion of subjects with the same or reduced ADAS-cog14 score between ET-101 and Sham group. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ADAS-cog14 total score | ADAS-cog14: Total scores range from 0 to 90, with higher scores indicating more worsening. | 12 weeks | 
| Proportion of subjects with decreased ADAS-Cog score | ADAS-cog14: Total scores range from 0 to 90, with higher scores indicating more worsening. | 12 weeks | 
| Proportion of subjects with increased K-MMSEII score | Korean Mini-Mental State Examination 2nd edition (K-MMSE): A score of 30 represents the least impairment and 0 represents the most severe impairment. | 12 weeks | 
| Change in CDR-SB | Clinical Dementia Rating-Sum of Boxes (CDR-SB): Total scores range from 0 to 18, with higher scores indicating more worsening. | 12 weeks | 
| Change in K-MMSEII | K-MMSE II: Total scores range from 0 to 30, with lower scores indicating more worsening. | 12 weeks | 
| CIBIC-plus score | Clinicians Interview-based Impression of Change (CIBIC-plus): The patient and their care giver are interviewed and questioned by the clinician. It evaluates global function and is scored from 1 (marked improvement) to 7 (marked worsening). The baseline value for CIBIC-plus is represented by Clinician's Interview-based Impression of Severity score (CIBIS). | 12 weeks | 
| Change in ADCOMS | Alzheimer's Disease Composite Score (ADCOMS): Composite scores range from 0.0 to 1.97, with higher scores indicating more worsening. | 12 weeks | 
| Change in DSC | Digit Symbol Coding (DSC): DSC test is sensitive to changes in information processing speed, provides measures of response speed and accuracy. A test score measures the number of correct responses in 120 seconds. A higher score indicates greater processing speed. | 12 weeks | 
| Change in ADCS-ADL | Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory Scale (ADCS-ADL): Total scores range from 0 to 78, with lower scores indicating worse function. | 12 weeks | 
| Change in EQ-5D | EuroQoL (Quality of Life)-5 Dimensions (EQ-5D): EQ-5D is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Total scores range from 3 (worst health state) to 1 (perfect health state). | 12 weeks |