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

Primary Purpose

Alzheimer Disease

Status

Unknown status

Phase

Not Applicable

Locations

Taiwan

Study Type

Interventional

Intervention

Transcranial Ultrasound Stimulation

About this trial

This is an interventional device feasibility trial for Alzheimer Disease focused on measuring Alzheimer's Disease, Transcranial Ultrasound Stimulation

Eligibility Criteria

55 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Taipei Veterans General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

TUS treatment

Non-TUS treatment

Arm Description

AD patients with TUS treatment

AD patients with Non-TUS treatment

Outcomes

Primary Outcome Measures

Device and procedure related adverse events recording

Rate of adverse events following each treatment through end of study Clinical and MRI evaluation

Secondary Outcome Measures

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.

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.

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.

Transcranial Doppler (TCD)

Cerebral blood flow evaluation

Magnetic Resonance Image (MRI)

Brain observation

Full Information

NCT ID

NCT03896698

First Posted

March 28, 2019

Last Updated

April 26, 2020

Sponsor

National Yang Ming University

Collaborators

Taipei Veterans General Hospital, Taiwan

1. Study Identification

Unique Protocol Identification Number

NCT03896698

Brief Title

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

Acronym

TUS

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2020

Overall Recruitment Status

Unknown status

Study Start Date

August 23, 2019 (Actual)

Primary Completion Date

May 31, 2021 (Anticipated)

Study Completion Date

June 30, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

National Yang Ming University

Collaborators

Taipei Veterans General Hospital, Taiwan

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer Disease

Keywords

Alzheimer's Disease, Transcranial Ultrasound Stimulation

7. Study Design

Primary Purpose

Device Feasibility

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

TUS treatment

Arm Type

Experimental

Arm Description

AD patients with TUS treatment

Arm Title

Non-TUS treatment

Arm Type

No Intervention

Arm Description

AD patients with Non-TUS treatment

Intervention Type

Device

Intervention Name(s)

Transcranial Ultrasound Stimulation

Intervention Description

TUS activate the brain cells

Primary Outcome Measure Information:

Title

Device and procedure related adverse events recording

Description

Rate of adverse events following each treatment through end of study Clinical and MRI evaluation

Time Frame

up to 46 weeks after treatment

Secondary Outcome Measure Information:

Title

Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog)

Description

Time Frame

Change from baseline at 7, 12, 24, and 52 week

Title

Clinical Dementia Rating (CDR)

Description

Time Frame

Change from baseline at 12 and 52 week

Title

Neuropsychiatric Inventory Questionnaire (NPI-Q)

Description

Time Frame

Change from baseline at 12 and 52 week

Title

Transcranial Doppler (TCD)

Description

Cerebral blood flow evaluation

Time Frame

Changes in blood flow from baseline at 12 and 52 week

Title

Magnetic Resonance Image (MRI)

Description

Brain observation

Time Frame

Change from baseline at 12 and 52 week

10. Eligibility

Sex

All

Minimum Age & Unit of Time

55 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jong-Ling Fuh, M.D.

Phone

886-2-28762522

jlfuh@vghtpe.gov.tw

First Name & Middle Initial & Last Name or Official Title & Degree

Feng-Yi Yang, Ph.D.

Phone

886-2-28267281

fyyang@ym.edu.tw

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Feng-Yi Yang, Ph.D.

Organizational Affiliation

National Yang Ming University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Taipei Veterans General Hospital

City

Taipei

Country

Taiwan

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jong-Ling Fuh, M.D.

First Name & Middle Initial & Last Name & Degree

Jong-Li Fuh, M.D.

12. IPD Sharing Statement

Citations:

PubMed Identifier

30873554

Citation

Chen TT, Lan TH, Yang FY. Low-Intensity Pulsed Ultrasound Attenuates LPS-Induced Neuroinflammation and Memory Impairment by Modulation of TLR4/NF-kappaB Signaling and CREB/BDNF Expression. Cereb Cortex. 2019 Apr 1;29(4):1430-1438. doi: 10.1093/cercor/bhy039.

Results Reference

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PubMed Identifier

29615782

Citation

Chen CM, Wu CT, Yang TH, Liu SH, Yang FY. Preventive Effect of Low Intensity Pulsed Ultrasound against Experimental Cerebral Ischemia/Reperfusion Injury via Apoptosis Reduction and Brain-derived Neurotrophic Factor Induction. Sci Rep. 2018 Apr 3;8(1):5568. doi: 10.1038/s41598-018-23929-8.

Results Reference

background

PubMed Identifier

29383687

Citation

Chen SF, Su WS, Wu CH, Lan TH, Yang FY. Transcranial Ultrasound Stimulation Improves Long-Term Functional Outcomes and Protects Against Brain Damage in Traumatic Brain Injury. Mol Neurobiol. 2018 Aug;55(8):7079-7089. doi: 10.1007/s12035-018-0897-z. Epub 2018 Jan 30.

Results Reference

background

PubMed Identifier

29138458

Citation

Su WS, Wu CH, Chen SF, Yang FY. Low-intensity pulsed ultrasound improves behavioral and histological outcomes after experimental traumatic brain injury. Sci Rep. 2017 Nov 14;7(1):15524. doi: 10.1038/s41598-017-15916-2.

Results Reference

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PubMed Identifier

28939348

Citation

Su WS, Wu CH, Chen SF, Yang FY. Transcranial ultrasound stimulation promotes brain-derived neurotrophic factor and reduces apoptosis in a mouse model of traumatic brain injury. Brain Stimul. 2017 Nov-Dec;10(6):1032-1041. doi: 10.1016/j.brs.2017.09.003. Epub 2017 Sep 7.

Results Reference

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PubMed Identifier

27399328

Citation

Huang SL, Chang CW, Lee YH, Yang FY. Protective Effect of Low-Intensity Pulsed Ultrasound on Memory Impairment and Brain Damage in a Rat Model of Vascular Dementia. Radiology. 2017 Jan;282(1):113-122. doi: 10.1148/radiol.2016160095. Epub 2016 Jul 11.

Results Reference

background

PubMed Identifier

27252349

Citation

Liu SH, Lai YL, Chen BL, Yang FY. Ultrasound Enhances the Expression of Brain-Derived Neurotrophic Factor in Astrocyte Through Activation of TrkB-Akt and Calcium-CaMK Signaling Pathways. Cereb Cortex. 2017 Jun 1;27(6):3152-3160. doi: 10.1093/cercor/bhw169.

Results Reference

background

PubMed Identifier

26517350

Citation

Su WS, Tsai ML, Huang SL, Liu SH, Yang FY. Controllable permeability of blood-brain barrier and reduced brain injury through low-intensity pulsed ultrasound stimulation. Oncotarget. 2015 Dec 8;6(39):42290-9. doi: 10.18632/oncotarget.5978.

Results Reference

background

PubMed Identifier

25873429

Citation

Lin WT, Chen RC, Lu WW, Liu SH, Yang FY. Protective effects of low-intensity pulsed ultrasound on aluminum-induced cerebral damage in Alzheimer's disease rat model. Sci Rep. 2015 Apr 15;5:9671. doi: 10.1038/srep09671.

Results Reference

background

PubMed Identifier

25558041

Citation

Yang FY, Lu WW, Lin WT, Chang CW, Huang SL. Enhancement of Neurotrophic Factors in Astrocyte for Neuroprotective Effects in Brain Disorders Using Low-intensity Pulsed Ultrasound Stimulation. Brain Stimul. 2015 May-Jun;8(3):465-73. doi: 10.1016/j.brs.2014.11.017. Epub 2014 Dec 4.

Results Reference

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

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