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

NCT03896698 | Unknown DMC

• 1 other identifier: TUS01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer Disease

Keywords

Alzheimer's Disease; Transcranial Ultrasound Stimulation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

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

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

• Clinical Dementia Rating (CDR)

  Change from baseline at 12 and 52 week

• Neuropsychiatric Inventory Questionnaire (NPI-Q)

  Change from baseline at 12 and 52 week

• Transcranial Doppler (TCD)

  Changes in blood flow from baseline at 12 and 52 week

• Magnetic Resonance Image (MRI)

  Change from baseline at 12 and 52 week

Study Arms (2)

TUS treatment

EXPERIMENTAL

AD patients with TUS treatment

Device: Transcranial Ultrasound Stimulation

Non-TUS treatment

NO INTERVENTION

AD patients with Non-TUS treatment

Interventions

Transcranial Ultrasound Stimulation DEVICE

TUS activate the brain cells

TUS treatment

Eligibility Criteria

• Age: 55 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Yang Ming Chiao Tung University: lead
• Taipei Veterans General Hospital, Taiwan: collaborator

Study Sites (1)

Taipei Veterans General Hospital

Taipei, Taiwan

RECRUITING

Related Publications (10)

• 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.

  PMID: 30873554 BACKGROUND

• 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.

  PMID: 29615782 BACKGROUND

• 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.

  PMID: 29383687 BACKGROUND

• 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.

  PMID: 29138458 BACKGROUND

• 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.

  PMID: 28939348 BACKGROUND

• 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.

  PMID: 27399328 BACKGROUND

• 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.

  PMID: 27252349 BACKGROUND

• 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.

  PMID: 26517350 BACKGROUND

• 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.

  PMID: 25873429 BACKGROUND

• 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.

  PMID: 25558041 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Feng-Yi Yang, Ph.D.

  National Yang Ming Chiao Tung University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jong-Ling Fuh, M.D.

CONTACT

886-2-28762522; jlfuh@vghtpe.gov.tw

Feng-Yi Yang, Ph.D.

CONTACT

886-2-28267281; fyyang@ym.edu.tw

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DEVICE FEASIBILITY
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 28, 2019
• First Posted: April 1, 2019
• Study Start: August 23, 2019
• Primary Completion: May 31, 2021
• Study Completion: June 30, 2021
• Last Updated: April 28, 2020

Record last verified: 2020-04

Locations

TW (1)