Study to Evaluate the Efficacy and Safety of ATNC-MDD V1(TMS With Cognitive Training) in Mild Alzheimer's Dementia

Study Overview
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Brief Summary
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The study tests the effect of the ATNC MDD-V1 on Alzheimer patients' cognitive function. The ATNC MDD-V1 uses non-invasive stimulation of both magnetic and cognitive training.

Detailed Description
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The ATNC MDD-V1 system is a combined system of Transcranial Magnetic Stimulation and cognitive training and is a non-invasive therapeutic system for the improvement of Alzheimer patients' cognitive function. A potential participant will undergo screening procedures to confirm eligibility to participate in the study, followed by randomization procedure to one of the study groups - treatment or sham (placebo) Patient will attend the clinic 5 times a week for 6 weeks, approximately an hour every day for treatment/sham. The patient will be required to return to the clinic for follow-up. Up to 158 patients will be enrolled in up to 3 clinical sites in the Republic Korea.

Official Title
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Effects of a ATNC MDD-V1 (TMS With Cognitive Training), for the Treatment of Mild Alzheimer Disease: a Randomized, Double-blinded, Placebo-controlled Study

Conditions
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Alzheimer's Disease, Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Neurodegenerative Diseases, Neurocognitive Disorders, Mental Disorder

Intervention / Treatment
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* Device: ATNC MDD-V1 (Real TMS + Real Cog)
* Device: ATNC MDD-V1 (Sham TMS + Real Cog)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who started drug treatment with an acetylcholinesterase inhibitor at least 2 months before participating in the clinical trial and can participate in the clinical trial without changing the dose during the trial period. Male or female age 60-85 years. Patients diagnosed with mild stage of Alzheimer's Disease, according to the NIA-AA (2011) diagnosis. MMSE score 21 to 26. CDR 1 or GDS 3. Patients with a positive amyloid PET-CT. Patients who are judged physically capable of clinical trials based on medical records and examinations. Patient whose legal representative agrees to participate in a clinical trial and who can visit for the next observation with a guardian. Patients who agreed to participate in all 24-week clinical trials. Patients with normal ability to see and hear letters. Patients who speak Korean as their mother tongue Exclusion Criteria: Patients with a central nervous system disease that can affect cognitive function and is likely to be another cause of cognitive decline, or a type of dementia other than Alzheimer's, is suspected. Patients who have been unconscious due to brain surgery or concussion, or who have signs or symptoms of cranial pressure elevation on neurologic examination. History of Epileptic Seizures or Epilepsy. Patients with a history of drug abuse, including alcohol, in the past 5 years from the time of screening. Patients with schizophrenia, schizoaffective disorder, bipolar disorder, current major depressive episode, psychosis, panic, post-traumatic stress, severe anxiety, mental retardation, DSM-V disorder. Patients with abnormal vitamin B12, folic acid deficiency, or thyroid stimulating hormone (TSH) test results that were considered by the investigator to affect or are caused by the severity of dementia. Patients with metal implants in the head, (i.e. cochlear implants, implanted brain stimulators and neurostimulators, aneurysm clips) with the exception of metal implants. Cardiac pacemakers. Implanted medication pumps. Intracardiac lines. Patients who are currently taking medications that lower the convulsive seizure threshold. Significant heart disease. Significant renal disease, Significant hepatic disease. Contraindication for performing MRI scanning. Contraindication for performing amyloid PET-CT scanning. Patients who do not consent to TMS treatment and participation in this clinical trial. Patients who participated in other clinical trials 3 months before participating in this clinical trial. Patients with a history of TMS treatment within the last 2 years before participating in this clinical trial. Patients judged by the investigator to be unsuitable for participation in clinical trials for other reasons. Patients with a history of malignant tumors within the last 5 years. - Participation is possible if more than 5 years have elapsed without recurrence after the decision to be cured (The point of complete removal of the tumor through surgery or the end of chemotherapy, etc.). Patients who need to take medications suggested in concomitantly contraindicated drugs.

Ages Eligible for Study
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Minimum Age: 60 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ATNC MDD-V1<br>ATNC MDD-V1 treatment, synchronized TMS and cognitive training stimulation | Device: ATNC MDD-V1 (Real TMS + Real Cog)<br>* Synchronized TMS and cognitive stimulation to 6 brain areas.<br>* Other names: Brain Sense & Brain Cog;|
| Sham Comparator: Sham TMS + Real Cog<br>The Control arm subjects will receive daily treatments five days a week for 6 consecutive weeks of Sham treatment of TMS and real cognitive training which is similar to the real treatment in visit frequency and procedure. | Device: ATNC MDD-V1 (Sham TMS + Real Cog)<br>* Sham device, has the same appearance and sound as the real device, combined with real cognitive exercises. Patients come for the same number of sessions, delivers no real stimulation or cognitive training.<br>* Other names: sham;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer's Disease Assessment Scale-Cognition Score (Efficacy) | Change from Baseline to 24 weeks in ADAS-Cog score. ADAS-Cog: Alzheimer's Disease Assessment Scale - Cognitive | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer's Disease Assessment Scale-Cognitive(ADAS-cog) Score (Efficacy) | Change from Baseline to 7,12 weeks in ADAS-Cog score. ADAS-Cog: Alzheimer's Disease Assessment Scale - Cognitive | Week 7, 12 | 
| Korean-Mini Mental State Examination-2nd Edition(K-MMSE-2)(Efficacy) | Change from Baseline to 7, 12 and 24 weeks in K-MMSE-2. K-MMSE-2: Korean-Mini Mental State Examination-2nd Edition | Week 7, 12, 24 | 
| Clinical Dementia Rating(CDR)(Efficacy) | Change from Baseline to 7, 12 and 24 weeks in CDR. CDR: Clinical Dementia Rating | Week 7, 12, 24 | 
| Global Deterioration Scale(GDeps)(Efficacy) | Change from Baseline to 7, 12 and 24 weeks in GDeps. GDeps: Global Deterioration Scale | Week 7, 12, 24 | 
| Clinical Global Impression of Change(CGIC)(Efficacy) | Change from Baseline to 7, 12 and 24 weeks in CGIC CGIC: Clinical Global Impression of Change | Week 7, 12, 24 | 
| Korean-Instrumental Activities of Daily Living(K-IADL)(Efficacy) | Change from Baseline to 7, 12 and 24 weeks in K-IADL. K-IADL: Korean-Instrumental Activities of Daily Living | Week 7, 12, 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TMS, Cognitive Stimulation, ATNC MDD-V1, Dementia