A Pivotal Study of LIPUS-Brain in Patients With Early Alzheimer's Disease

Study Overview
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Brief Summary
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This study is a multicenter, randomized, double-blinded, placebo-controlled Phase 3 study comparing LIPUS-Brain transcranial low-intensity pulsed-wave ultrasound device to placebo in patients with Early Alzheimer's Disease. The primary objective of the study is to assess changes in ADAS-J-cog-14 scores from baseline to 72 weeks.

Official Title
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A Study to Evaluate the Efficacy and Safety of LIPUS-Brain Transcranial Low-intensity Pulsed-wave Ultrasound Device in Patients With Early Alzheimer's Disease

Conditions
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Alzheimer Disease, Early Onset

Intervention / Treatment
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* Device: LIPUS-Brain
* Device: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent to participate in the clinical trial from the patient and their legal representative. Mild AD or MCI due to AD patient aged greater than or equal to (>=) 50 and less than (<) 90 years, at the time of informed consent. Patients with the same partner/informant who meet all of the following conditions during the study period Living with or in contact with the patient It is possible to observe the patient's activities of daily living and physical condition. Being able to be present at all times during the efficacy evaluation specified in this clinical trial Person judged by an investigator to be able to manage administration of concomitant medications Patients who met the diagnostic criteria of Mild AD or MCI due to AD according to the NIA/AA 2018 diagnostic criteria at the time of informed consent and were diagnosed as positive by the amyloid PET imaging evaluation committee. Have a CDR global score of 0.5 (MCI due to AD) to 1.0 (Mild AD) at screening. Patients with her MMSE-J score >=20 at screening. No organic diseases such as symptomatic cerebral hemorrhage, symptomatic cerebral infarction, acute cerebral infarction, brain tumor, etc. within 48 weeks before obtaining informed consent or in head MRI images at screening, and in head MRA images, Patients evaluated by the imaging evaluation committee as not having severe stenosis/occlusion from the internal carotid artery to the middle cerebral artery. Patients who are receiving existing drug therapy for Mild AD or MCI due to AD and are not scheduled to change their medication within the past 4 weeks from obtaining consent and after obtaining consent. Exclusion Criteria: Patients judged by the investigator that it is difficult to continue the study treatment for 20 minutes. Patients judged by the investigator to be difficult to perform an MRI examination. Patients with impaired consciousness with a GCS score of 12 or less at the time of enrollment. Patients who have had symptomatic cerebral infarction or cerebral hemorrhage within 12 weeks prior to enrollment. Patients with a modified Hachinski Ischemic Scale score of 5 or more at enrollment. Patients with Lewy body dementia and frontotemporal dementia. Patients judged by the investigator to be difficult to participate in the clinical trial due to severe mental illness Poorly controlled serious systemic disease (heart failure, liver failure, renal failure, vitamin B12 deficiency, hypothyroidism, etc.) that makes it difficult for the investigator to participate in the study judged patient. Patients with uncontrolled diabetic retinopathy (with active fundus hemorrhage). Patients who have malignant tumor as a complication or who have been treated for malignant tumor within 5 years from the time of enrollment (excluding cured resected carcinoma in situ). Patients who are or have a history of drug addiction or alcohol addiction. Patients with or with a history of epilepsy. Patients with implants such as coils, electrodes and stents in the skull. Patients within 5 years after brain surgery (including endovascular treatment). Patients who are pregnant or wish to become pregnant. Patients participating in other clinical studies (excluding non-interventional observational studies) or clinical trials. Patients who are otherwise judged to be ineligible by the investigator.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 89 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LIPUS-Brain<br> | Device: LIPUS-Brain<br>* Transcranial low-power pulsed-wave ultrasound device<br>|
| Placebo Comparator: Placebo<br> | Device: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in ADAS-J-cog-14 scores from baseline to Week 72 |  | Performed at Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in ADAS-J-cog-14 scores from baseline to Week 24 and 48 |  | Performed at Week 24 and 48 | 
| Changes in CDR-SB from baseline to Week 48 and 72 |  | Performed at Week 48 and 72 | 
| Changes in NPIQ-J scores from baseline to Week 24, 48 and 72 |  | Performed at Week 24, 48 and 72 | 
| Changes in J-ZBI scores from baseline to Week 24, 48 and 72 |  | Performed at Week 24, 48 and 72 | 
| Changes in WMS-R scores from baseline to Week 24, 48 and 72 |  | Performed at Week 24, 48 and 72 | 
| Changes in MMSE-J scores from baseline to Week 24, 48 and 72 |  | Performed at Week 24, 48 and 72 | 
| Changes in FAQ scores from baseline to Week 24, 48 and 72 |  | Performed at Week 24, 48 and 72 | 
| Changes in EQ-5D-5L scores from baseline to Week 24, 48 and 72 |  | Performed at Week 24, 48 and 72 | 
| Changes in ABC Dementia scale scores from baseline to Week 24, 48 and 72 |  | Performed at Week 24, 48 and 72 | 
| Changes in each 14 item of ADAS-J-cog-14 score from baseline to Week 24, 48 and 72 |  | Performed at Week 24, 48 and 72 | 
| Prevalence of responders at Week 24, 48, and 72 defined as those with no deterioration or even improvement in ADAS-J-cog-14 scores |  | Performed at Week 24, 48 and 72 | 
| Transition rate from MCI due to AD to AD at Week 72 |  | Performed at Week 72 | 
| Termination due to aggravation of dementia symptoms | If medication needs to be started or changed, dementia is considered worsening. | Performed up to 96 weeks |