Low-intensity Hippocampal Transcranial Ultrasound Stimulation for Managing Cognitive and Sleep Dysfunction in Preclinical Alzheimer's Disease

NCT ID: NCT07298876

Last Updated: 2025-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ENROLLING_BY_INVITATION

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-04-01

Study Completion Date

2027-05-16

Brief Summary

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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

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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

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Sleep Disturbances Aging Cognitive Impairment, Mild

Keywords

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Sleep disturbances Aging Transcranial ultrasound stimulation Hippocampus Central Nervous System Diseases Randomized clinical trial Personalized medicine Cognitive impairments Glymphatic function

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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Active TUS

In active TUS group, participants will receive 500 kHz low-intensity TUS.

Group Type ACTIVE_COMPARATOR

Low-intensity transcranial ultrasound stimulation

Intervention Type DEVICE

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 TUS

In sham TUS group, participants will receive sham TUS.

Group Type SHAM_COMPARATOR

Sham low-intensity transcranial ultrasound stimulation

Intervention Type DEVICE

Sham TUS uses the same settings as the active low-intensity TUS. During the sham treatment, the power will be off.

Interventions

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Low-intensity transcranial ultrasound stimulation

Low-intensity TUS, as an advanced modality of transcranial brain stimulation, enables to stimulate the deep brain structures with optimized focality and specific frequency.

Intervention Type DEVICE

Sham low-intensity transcranial ultrasound stimulation

Sham TUS uses the same settings as the active low-intensity TUS. During the sham treatment, the power will be off.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

60 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Hong Kong Polytechnic University

OTHER

Sponsor Role collaborator

Chinese University of Hong Kong

OTHER

Sponsor Role lead

Responsible Party

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LU Hanna

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Tai Po Hospital

Hong Kong, Tai Po District, Hong Kong

Site Status

Countries

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Hong Kong

Other Identifiers

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2024.652

Identifier Type: -

Identifier Source: org_study_id