Feasibility Study of Transcranial Ultrasound Stimulation on Alzheimer's Disease Patients

Study Overview
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Brief Summary
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Currently, the main treatment method for Alzheimer's disease (AD) is chemotherapy. However, the effectiveness of drugs is moderate and there are several side effects. In this clinical trial, the investigators would like to activate the brain by the transcranial ultrasound stimulation (TUS). This is a feasibility study to evaluate the safety and initial effectiveness of TUS for the treatment of patients with mild AD.

Detailed Description
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The purpose of this study is to verify the feasibility of low intensity transcranial ultrasound stimulation (TUS) for patients with mild Alzheimer's disease (AD). As a secondary aim, the investigators will explore whether the TUS is associated with improvement in cognitive functioning six and forty-six weeks following the intervention. Subjects will be randomly assigned to one of two experimental groups which with or without the TUS administration. The investigators will study up to 20 subjects with mild AD. Initially, subjects will undergo a screening assessment with a study physician to determine medical and psychiatric history, establish AD diagnosis, and undergo a bold draw. Subjects that meet criteria and agree to participate in the study will undergo a follow-up visit. In the baseline measurement visit, participants will first undergo neuropsychological testing. Participants will be randomly assigned to one of two groups. Participants will then be administrated TUS treatment for six weeks. Subsequently, participants will undergo a series of neuropsychological test. A final follow-up assessment will be administered at forty-six weeks.

Official Title
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Feasibility Study of Transcranial Ultrasound Stimulation on Alzheimer's Disease Patients

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Device: Transcranial Ultrasound Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 55 and 90 years old Weight greater than 50 kg Male or Female Good understanding of written and verbal Chinese Geriatric Depression Scale (GDS) score of < 8 Mild AD patients (Mini-Mental State Examination (MMSE) 20-26) Probable AD consistent with NIA/AA criteria The blood flow of bilateral middle cerebral artery M1 can be detected by Transcranial Color Doppler (TCD) Caregiver spending at least 10 hours per week with the patient Agreement to obey the rules of this study Use of cholinesterase inhibitors for AD (Aricept, Namenda, etc.) will be allowed as long as the participant has been on a stable dose for at least six months Does have a reliable caregiver in frequent contact with the patient and can accompany the patient to the clinic and treatment Exclusion Criteria: Evidence of any other major neurologic or other physical illness that could produce cognitive deterioration, except for mild cognitive impairment (MCI) and any history of stroke or diabetes History of myocardial infarction within the previous year or unstable cardiac disease Any contraindications to MRI scanning such as metallic implants, claustrophibia or too large for MRI scanner History of liver disease or severely impaired renal function The blood flow of either unilateral middle cerebral artery M1 can't be detected by Transcranial Color Doppler (TCD) Major psychiatric disorders, such as bipolar disorder or schizophrenia, or persons with current untreated major depression Pregnant or breastfeeding women

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 90 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: Device Feasibility
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TUS treatment<br>AD patients with TUS treatment | Device: Transcranial Ultrasound Stimulation<br>* TUS activate the brain cells<br>|
| No Intervention: Non-TUS treatment<br>AD patients with Non-TUS treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device and procedure related adverse events recording | Rate of adverse events following each treatment through end of study Clinical and MRI evaluation | up to 46 weeks after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) | ADAS was designed to measure the severity of the most important symptoms of Alzheimer's disease (AD). Its subscale ADAS-cog is the most popular cognitive testing instrument used in clinical trials of nootropics. It consists of 11 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities which are often referred to as the core symptoms of AD. The test administrator adds up points for the errors in each task of the ADAS-Cog for a total score. Total scores range from 0-70. The greater the dysfunction, the greater the score. | Change from baseline at 7, 12, 24, and 52 week | 
| Clinical Dementia Rating (CDR) | The Clinical Dementia Rating or CDR is a numeric scale used to quantify the severity of symptoms of dementia (i.e. its 'stage'). Using a structured-interview protocol, qualified health professional assesses a patient's cognitive and functional performance in six areas: memory, orientation, judgment & problem solving, community affairs, home & hobbies, and personal care. Scores in each of these are combined to obtain a composite score ranging from 0 through 3, with 0 meaning of no symptoms, 0.5 very mild dementia, 1 mild dementia, 2 moderate dementia and 3 severe dementia. | Change from baseline at 12 and 52 week | 
| Neuropsychiatric Inventory Questionnaire (NPI-Q) | NPI-Q is a carer-based tool that assesses the possible presence of 12 symptoms in dementia cases, including delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, night-time behavioral disturbances and appetite/eating disturbances. The severity scale has scores ranging from 1 to 3 points (1=mild; 2=moderate; and 3=severe) and the scale for assessing caregiver distress has scores ranging from 0 to 5 points (0=no distress; 1=minimal distress; 2=mild distress; 3=moderate distress; 4=severe distress; and 5=extreme distress). The total scores of severity and caregiver stress are summed of each 12 items separately, with with higher scores indicating a greater number of neuropsychiatric symptoms or distress. | Change from baseline at 12 and 52 week | 
| Transcranial Doppler (TCD) | Cerebral blood flow evaluation | Changes in blood flow from baseline at 12 and 52 week | 
| Magnetic Resonance Image (MRI) | Brain observation | Change from baseline at 12 and 52 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease, Transcranial Ultrasound Stimulation