Alzheimer DiseaseTUSNCT03896698
Feasibility Study of Transcranial Ultrasound Stimulation on Alzheimer's Disease Patients
A study testing Transcranial Ultrasound Stimulation in people with Alzheimer Disease, run by National Yang Ming Chiao Tung University at 1 site in Taiwan.
Trial 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). Read more about this study
- Who is it for?
- Ages 55 to 90 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Transcranial Ultrasound Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteTaiwan
- Study dates
- 23 Aug 2019to 30 Jun 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 12Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Taipei Veterans General Hospital
Taipei
Jong-Ling Fuh, M.D.
Jong-Li Fuh, M.D.
About this study
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.
Read the 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.
- Conditions
- Alzheimer Disease
- Being tested
- Transcranial Ultrasound Stimulation
- Keywords
- Alzheimer's Disease, Transcranial Ultrasound Stimulation
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Ultrasound StimulationDevice
TUS activate the brain cells
| Study group | Role | What they receive |
|---|---|---|
| TUS treatment | Experimental | AD patients with TUS treatment Receives: Device: Transcranial Ultrasound Stimulation |
| Non-TUS treatment | No intervention | AD patients with Non-TUS treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Device and procedure related adverse events recording
Rate of adverse events following each treatment through end of study Clinical and MRI evaluation
Measured: up to 46 weeks after treatment
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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.
Measured: Change from baseline at 12 and 52 week
Transcranial Doppler (TCD)
Cerebral blood flow evaluation
Measured: Changes in blood flow from baseline at 12 and 52 week
Magnetic Resonance Image (MRI)
Brain observation
Measured: Change from baseline at 12 and 52 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2019
- Study start23 Aug 2019
- Primary completion31 May 2021 (estimated)
- Study completion30 Jun 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by National Yang Ming Chiao Tung UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Device feasibility
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Yang Ming Chiao Tung University
- Sponsor type
- University, hospital or other
- Collaborators
- Taipei Veterans General Hospital, Taiwan
- Responsible party
- Principal investigator, Feng-Yi Yang, National Yang Ming Chiao Tung University
- Investigators
- Feng-Yi Yang, Ph.D., Principal investigator, National Yang Ming Chiao Tung University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03896698
- Sponsor's protocol ID
- TUS01
- Acronym
- TUS
- Status last verified
- Apr 2020
- First submitted
- 28 Mar 2019
- Last updated
- 28 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 30873554Chen 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.
PubMed 29615782Chen 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.
PubMed 29383687Su 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.
PubMed 29138458Su 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.
PubMed 28939348Huang 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.
PubMed 27399328Liu 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.
PubMed 27252349Su 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.
PubMed 26517350Lin 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.
PubMed 25873429Yang 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.
PubMed 25558041
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility Study of Transcranial Ultrasound Stimulation on Alzheimer's Disease Patients
- ClinicalTrials.gov ID
- NCT03896698
- Acronym / sponsor ID
- TUS / TUS01
- Conditions
- Alzheimer Disease
- Keywords
- Alzheimer's Disease, Transcranial Ultrasound Stimulation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- National Yang Ming Chiao Tung UniversityUniversity, hospital or other
- Collaborators
- Taipei Veterans General Hospital, Taiwan
- Study start
- 23 Aug 2019 (actual)
- Primary completion
- 31 May 2021 (estimated)
- Study completion
- 30 Jun 2021 (estimated)
- First posted
- 1 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Device feasibility
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TUS treatment | Experimental | Device: Transcranial Ultrasound StimulationAD patients with TUS treatment |
| Non-TUS treatment | No intervention | –AD patients with Non-TUS treatment |
Who may qualify
- Ages
- 55 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Ultrasound StimulationTUS activate the brain cells | Device | TUS treatment |
Primary outcome
Device and procedure related adverse events recording
Time frame: up to 46 weeks after treatment
Rate of adverse events following each treatment through end of study Clinical and MRI evaluation
5 secondary outcomes
Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog)
Time frame: Change from baseline at 7, 12, 24, and 52 week
Clinical Dementia Rating (CDR)
Time frame: Change from baseline at 12 and 52 week
Neuropsychiatric Inventory Questionnaire (NPI-Q)
Time frame: Change from baseline at 12 and 52 week
Transcranial Doppler (TCD)
Time frame: Changes in blood flow from baseline at 12 and 52 week
Magnetic Resonance Image (MRI)
Time frame: Change from baseline at 12 and 52 week
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2020.
- Background: PubMed 30873554Chen 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.
- Background: PubMed 29615782Chen 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.
- Background: PubMed 29383687Chen 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.
- Background: PubMed 29138458Su 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.
- Background: PubMed 28939348Su 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.
- Background: PubMed 27399328Huang 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.
- Background: PubMed 27252349Liu 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.
- Background: PubMed 26517350Su 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.
- Background: PubMed 25873429Lin 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.
- Background: PubMed 25558041Yang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Feng-Yi Yang, Ph.D. principal investigator
National Yang Ming Chiao Tung University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Ultrasound Stimulation in people with Alzheimer Disease, run by National Yang Ming Chiao Tung University at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jong-Ling Fuh, M.D. (886-2-28762522, jlfuh@vghtpe.gov.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Device and procedure related adverse events recording (time frame: up to 46 weeks after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03896698, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2020.