Sleep DisturbancesNCT07298876
Low-intensity Hippocampal Transcranial Ultrasound Stimulation for Managing Cognitive and Sleep Dysfunction in Preclinical Alzheimer's Disease
A study testing Low-intensity transcranial ultrasound stimulation in people with Sleep Disturbances and Aging, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial summary
Background: Sleep disturbances, as a common symptom, can jeopardize the brain health and cognitive function and even lead to cognitive impairments in older adults. The co-occurring sleep disturbances cognitive complaints can significantly affect brain functions, and even be implicated as a key contributing factor in… Read more about this study
- Who is it for?
- Ages 60 to 85 years
- Conditions the study is for
- Sleep Disturbances, Aging, Cognitive Impairment, Mild
- What is being tested?
- Low-intensity transcranial ultrasound stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Apr 2026to 16 May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 60 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chinese, right-handed, aged from 60 to 85 years.
- Mild neurocognitive disorder due to Alzheimer's disease (NCD-AD) is identified with the Montreal Cognitive Assessment (MoCA) score range from 22 to 26.
- Sleep disturbances or poor sleep quality is assessed and defined with a total score of the Pittsburgh Sleep Quality Index (PSQI) greater than 5.
- No impairments in the activities of daily living.
Who cannot join
- Previous diagnosis of age-related neurodegenerative diseases, such as Alzheimer's disease, Parkinson disease.
- History of neurological diseases including brain tumor, and stroke.
- History of psychiatric disorders including schizophrenia and depression.
- Presence of positive neurological diseases, such as stroke, brain tumor, dementia.
- Physically unable to attend the sessions of intervention.
- Currently enrolled in another intervention study.
- Currently taking a psychiatric or other medication that may affect sleep quality and cognition.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Low-intensity Hippocampal Transcranial Ultrasound Stimulation for Managing Cognitive and Sleep Dysfunction in Preclinical Alzheimer's Disease Patients: A Randomized Clinical Trial
Background: Sleep disturbances, as a common symptom, can jeopardize the brain health and cognitive function and even lead to cognitive impairments in older adults. The co-occurring sleep disturbances cognitive complaints can significantly affect brain functions, and even be implicated as a key contributing factor in the development of prodromal Alzheimer's disease (AD). At present, very few non-pharmacological therapies are developed for managing these comorbidities in older adults. Focused low-intensity transcranial ultrasound stimulation (TUS) enables to stimulation the deep brain structures, such as hippocampus, with optimized focality and specific frequency.
Objectives: 1) To investigate the safety, feasibility and efficacy of a 2-week focused low-intensity hippocampal TUS on the severity of sleep disturbances and cognitive impairments in elderly patients; 2) to determine the sample size of a full-scale randomized clinical trial of low-intensity TUS in patients with preclinical AD; 3) to evaluate the effects of low-intensity TUS on the severity of sleep quality and cognitive functions at 2, 6 and 10 weeks after the treatments.
Design: A 2-week randomized, double-blind, controlled clinical trial. Methods: Chinese right-handed preclinical AD patients with sleep disturbances (aged from 60 to 90 years) will be randomly assigned to a 2-week intervention of either low intensity TUS or sham TUS, with 10 participants per arm. Before intervention, T1-weighted magnetic resonance imaging (MRI) data is used to construct individual realistic head model. Comprehensive assessments, including sleep quality, cognitive performance and plasma p-tau217, Aß42 and Aß40 will be conducted at baseline, 2nd week, 6th week and 10th week. Program adherence and adverse effects will be monitored throughout intervention.
Read the detailed description
Significance: This study aims to investigate the feasibility, safety and efficacy of low intensity hippocampal TUS for sleep disturbances and cognitive impairments in patients with preclinical Alzheimer's disease. It wills also test the program adherence, tolerability and adverse effects of this innovative neuromodulation. Information will be helpful for in-depth understanding the relationship of "sleep, glymphatic function and cognition" and guiding the further studies of neurodegenerative diseases and sleep medicine.
Data analysis: The primary outcomes will be the changes in sleep quality and cognition, and the comparisons of group differences across different time points. Secondary outcomes will be the changes of glymphatic function and neuropathological factors. Intention-to-treat analysis will be carried out. Changes of efficacy indicators from baseline to each follow up point will be tested with mixed effect model.
- Conditions
- Sleep Disturbances, Aging, Cognitive Impairment, Mild
- Being tested
- Low-intensity transcranial ultrasound stimulation, Sham low-intensity transcranial ultrasound stimulation
- Keywords
- Sleep disturbances, Aging, Transcranial ultrasound stimulation, Hippocampus, Central Nervous System Diseases, Randomized clinical trial, Personalized medicine, Cognitive impairments, Glymphatic function
- Medical subject headings
- Parasomnias, Cognitive Dysfunction, Central Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-intensity transcranial ultrasound stimulationDevice
Low-intensity TUS, as an advanced modality of transcranial brain stimulation, enables to stimulate the deep brain structures with optimized focality and specific frequency.
Sham low-intensity transcranial ultrasound stimulationDevice
Sham TUS uses the same settings as the active low-intensity TUS. During the sham treatment, the power will be off.
| Study group | Role | What they receive |
|---|---|---|
| Active TUS | Active comparator | In active TUS group, participants will receive 500 kHz low-intensity TUS. Receives: Device: Low-intensity transcranial ultrasound stimulation |
| Sham TUS | Sham comparator | In sham TUS group, participants will receive sham TUS. Receives: Device: Sham low-intensity transcranial ultrasound stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pittsburg Sleep Quality Index (PSQI)
Description: The PSQI is a 19-item questionnaire that includes seven areas of subjective sleep quality and patterns in adults over the last month including the following components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, SDs, use of sleeping medications, and daytime dysfunction. Each item in the scale is scored from 0 to 3 scale (0 = no difficulty; 3 = severe difficulty). The scores are added to yield a global score ranging from 0 to 21 (0 = no difficulty; 21 = severe difficulties in all areas). This scale has good reliability and validity psychometrics and is widely used in research: Cronbach's alpha (0.77 to 0.83), sensitivity (89.6%), specificity (86.5%). Greater score of PSQI indicates worse sleep quality.
Measured: 10 weeks
Delayed recall of the words
Word-list learning test (WLLT), consisting of sixteen semantically non-associated words that is presented consecutively over three free trials of immediate recall, a 20-min delayed recall (to prevent recency effects). Delayed recall of the words derived from WLLT is used as a proxy for measuring working memory function.
Measured: 10 weeks
Secondary outcomes (3)
Objective sleep quality
Actigraphy records will be used to quantify sleep-wake cycle during treatment.
Measured: 2 weeks
The levels of plasma Aß
The levels of plasma Aß, including Aß42, Aß40 and Aß42/40 ratio, are assessed at the baseline and post-intervention time points.
Measured: 10 weeks
The levels of plasma tau
The levels of plasma tau, are assessed at the baseline and post-intervention time points.
Measured: 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2025
- Study start1 Apr 2026 (estimated)
- Primary completion31 Mar 2027 (estimated)
- Study completion16 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sleep DisturbancesStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- The Hong Kong Polytechnic University
- Responsible party
- Principal investigator, LU Hanna, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07298876
- Sponsor's protocol ID
- 2024.652
- Status last verified
- Sep 2025
- First submitted
- 1 Sep 2025
- Last updated
- 23 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: This clinical trial will have patients' information.
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low-intensity Hippocampal Transcranial Ultrasound Stimulation for Managing Cognitive and Sleep Dysfunction in Preclinical Alzheimer's Disease Patients: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT07298876
- Acronym / sponsor ID
- 2024.652
- Conditions
- Sleep Disturbances, Aging, Cognitive Impairment, Mild
- Keywords
- Sleep disturbances, Aging, Transcranial ultrasound stimulation, Hippocampus, Central Nervous System Diseases, Randomized clinical trial, Personalized medicine, Cognitive impairments
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Collaborators
- The Hong Kong Polytechnic University
- Study start
- 1 Apr 2026 (estimated)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 16 May 2027 (estimated)
- First posted
- 23 Dec 2025 (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.
Background: Sleep disturbances, as a common symptom, can jeopardize the brain health and cognitive function and even lead to cognitive impairments in older adults. The co-occurring sleep disturbances cognitive complaints can significantly affect brain functions, and even be implicated as a key contributing factor in the development of prodromal Alzheimer's disease (AD). At present, very few non-pharmacological therapies are developed for managing these comorbidities in older adults. Focused low-intensity transcranial ultrasound stimulation (TUS) enables to stimulation the deep brain structures, such as hippocampus, with optimized focality and specific frequency.
Objectives: 1) To investigate the safety, feasibility and efficacy of a 2-week focused low-intensity hippocampal TUS on the severity of sleep disturbances and cognitive impairments in elderly patients; 2) to determine the sample size of a full-scale randomized clinical trial of low-intensity TUS in patients with preclinical AD; 3) to evaluate the effects of low-intensity TUS on the severity of sleep quality and cognitive functions at 2, 6 and 10 weeks after the treatments.
Design: A 2-week randomized, double-blind, controlled clinical trial. Methods: Chinese right-handed preclinical AD patients with sleep disturbances (aged from 60 to 90 years) will be randomly assigned to a 2-week intervention of either low intensity TUS or sham TUS, with 10 participants per arm. Before intervention, T1-weighted magnetic resonance imaging (MRI) data is used to construct individual realistic head model. Comprehensive assessments, including sleep quality, cognitive performance and plasma p-tau217, Aß42 and Aß40 will be conducted at baseline, 2nd week, 6th week and 10th week. Program adherence and adverse effects will be monitored throughout intervention.
Detailed description
Significance: This study aims to investigate the feasibility, safety and efficacy of low intensity hippocampal TUS for sleep disturbances and cognitive impairments in patients with preclinical Alzheimer's disease. It wills also test the program adherence, tolerability and adverse effects of this innovative neuromodulation. Information will be helpful for in-depth understanding the relationship of "sleep, glymphatic function and cognition" and guiding the further studies of neurodegenerative diseases and sleep medicine.
Data analysis: The primary outcomes will be the changes in sleep quality and cognition, and the comparisons of group differences across different time points. Secondary outcomes will be the changes of glymphatic function and neuropathological factors. Intention-to-treat analysis will be carried out. Changes of efficacy indicators from baseline to each follow up point will be tested with mixed effect model.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active TUS | Active comparator | Device: Low-intensity transcranial ultrasound stimulationIn active TUS group, participants will receive 500 kHz low-intensity TUS. |
| Sham TUS | Sham comparator | Device: Sham low-intensity transcranial ultrasound stimulationIn sham TUS group, participants will receive sham TUS. |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Chinese, right-handed, aged from 60 to 85 years.
- Mild neurocognitive disorder due to Alzheimer's disease (NCD-AD) is identified with the Montreal Cognitive Assessment (MoCA) score range from 22 to 26.
- Sleep disturbances or poor sleep quality is assessed and defined with a total score of the Pittsburgh Sleep Quality Index (PSQI) greater than 5.
- No impairments in the activities of daily living.
Key exclusion criteria (7 listed)
- Previous diagnosis of age-related neurodegenerative diseases, such as Alzheimer's disease, Parkinson disease.
- History of neurological diseases including brain tumor, and stroke.
- History of psychiatric disorders including schizophrenia and depression.
- Presence of positive neurological diseases, such as stroke, brain tumor, dementia.
- Physically unable to attend the sessions of intervention.
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 |
|---|---|---|
| Low-intensity transcranial ultrasound stimulationLow-intensity TUS, as an advanced modality of transcranial brain stimulation, enables to stimulate the deep brain structures with optimized focality and specific frequency. | Device | Active TUS |
| Sham low-intensity transcranial ultrasound stimulationSham TUS uses the same settings as the active low-intensity TUS. During the sham treatment, the power will be off. | Device | Sham TUS |
Primary outcome
Pittsburg Sleep Quality Index (PSQI)
Time frame: 10 weeks
Description: The PSQI is a 19-item questionnaire that includes seven areas of subjective sleep quality and patterns in adults over the last month including the following components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, SDs, use of sleeping medications, and daytime dysfunction. Each item in the scale is scored from 0 to 3 scale (0 = no difficulty; 3 = severe difficulty). The scores are added to yield a global score ranging from 0 to 21 (0 = no difficulty; 21 = severe difficulties in all areas). This scale has good reliability and validity psychometrics and is widely used in research: Cronbach's alpha (0.77 to 0.83), sensitivity (89.6%), specificity (86.5%). Greater score of PSQI indicates worse sleep quality.
Delayed recall of the words
Time frame: 10 weeks
Word-list learning test (WLLT), consisting of sixteen semantically non-associated words that is presented consecutively over three free trials of immediate recall, a 20-min delayed recall (to prevent recency effects). Delayed recall of the words derived from WLLT is used as a proxy for measuring working memory function.
3 secondary outcomes
Objective sleep quality
Time frame: 2 weeks
The levels of plasma Aß
Time frame: 10 weeks
The levels of plasma tau
Time frame: 10 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2025.
- Individual participant dataSharing planned: No. This clinical trial will have patients' information.
Related trials for Sleep Disturbances
Recruiting
Addressing Nocturia in Older Women Utilizing Behavioral Sleep Intervention and Brief Mindfulness
Nocturia, Insomnia
RecruitingObservational study
Locus Coeruleus and CCHS (Congenital Central Hypoventilation Syndrome)
Ondine Syndrome (Congenital Central Hypoventilation Syndrome)
Not yet recruiting
A Transdiagnostic Sleep Health Intervention for Veterans With PTSD
Stress Disorders, Post-Traumatic, Sleep Initiation and Maintenance Disorders
RecruitingObservational study
Development and Validation of a Multimodal Deep Learning Model Using Peripheral Oxygen Saturation and Ballistocardiography Signals for Predicting Apnea-Hypopnea Index in Obstructive Sleep Apnea
Obstructive Sleep Apnea
Not yet recruiting
Comprehensive Opioid Management and Breathing During Sleep
Sleep-Disordered Breathing, Chronic Opioid Use
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low-intensity transcranial ultrasound stimulation in people with Sleep Disturbances and Aging, run by Chinese University of Hong Kong at 1 site in Hong Kong.
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 4 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: enrolling by invitation, as of the sponsor's last update on 23 Dec 2025. 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 Hong Kong. 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. Some participants in this study may receive a placebo. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pittsburg Sleep Quality Index (PSQI) (time frame: 10 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Dec 2025.