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

Not Applicable

• Conditions: Alzheimer Disease
• Interventions: Device: Transcranial Ultrasound Stimulation

• Registration Number: NCT03896698
• Lead Sponsor: National Yang Ming Chiao Tung University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-03-28
• Study First Submitted QC: 2019-03-29
• Study First Posted: 2019-04-01
• Study Start: 2019-08-23
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-26
• Last Update Posted: 2020-04-28
• Primary Completion: 2021-05-31
• Study Completion: 2021-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Age between 55 and 90 years old
2. Weight greater than 50 kg
3. Male or Female
4. Good understanding of written and verbal Chinese
5. Geriatric Depression Scale (GDS) score of < 8
6. Mild AD patients (Mini-Mental State Examination (MMSE) 20-26)
7. Probable AD consistent with NIA/AA criteria
8. The blood flow of bilateral middle cerebral artery M1 can be detected by Transcranial Color Doppler (TCD)
9. Caregiver spending at least 10 hours per week with the patient
10. Agreement to obey the rules of this study
11. 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
12. Does have a reliable caregiver in frequent contact with the patient and can accompany the patient to the clinic and treatment

Exclusion Criteria

1. 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
2. History of myocardial infarction within the previous year or unstable cardiac disease
3. Any contraindications to MRI scanning such as metallic implants, claustrophibia or too large for MRI scanner
4. History of liver disease or severely impaired renal function
5. The blood flow of either unilateral middle cerebral artery M1 can't be detected by Transcranial Color Doppler (TCD)
6. Major psychiatric disorders, such as bipolar disorder or schizophrenia, or persons with current untreated major depression
7. Pregnant or breastfeeding women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TUS treatment	Transcranial Ultrasound Stimulation	AD patients with TUS treatment

Primary Outcome Measures

Name	Time	Method
Device and procedure related adverse events recording	up to 46 weeks after treatment	Rate of adverse events following each treatment through end of study Clinical and MRI evaluation

Secondary Outcome Measures

Name	Time	Method
Clinical Dementia Rating (CDR)	Change from baseline at 12 and 52 week	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.
Neuropsychiatric Inventory Questionnaire (NPI-Q)	Change from baseline at 12 and 52 week	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.
Transcranial Doppler (TCD)	Changes in blood flow from baseline at 12 and 52 week	Cerebral blood flow evaluation
Magnetic Resonance Image (MRI)	Change from baseline at 12 and 52 week	Brain observation
Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog)	Change from baseline at 7, 12, 24, and 52 week	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.

Trial Locations

Locations (1)

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan