Brain StimulationNCT05544201
Transcranial Alternating Current Stimulation (TACS) for Sleep Disturbances in Neurocognitive Disorders Due to Alzheimer's Disease
A study testing High-definition transcranial current stimulation in people with Brain Stimulation and Alzheimer Disease, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial summary
Background: Sleep disturbances are highly prevalent in ageing population and patients with age-related neurodegenerative diseases, which severely affect cognition and even lead to accumulated amyloid-β (Aβ). Read more about this study
- Who is it for?
- Ages 60 to 90 years
- Conditions the study is for
- Brain Stimulation, Alzheimer Disease, tACS
- What is being tested?
- High-definition transcranial current stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 99 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Oct 2022to 28 Feb 2024
- 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 60 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chinese, aged from 60 to 90 years.
- Mild neurocognitive disorder due to Alzheimer's disease (NCD-AD) is diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). NCD-AD patients are defined by the following criteria: (1) evidence of modest cognitive decline in at least one of six domains of cognition (memory, perceptual- motor, complex attention, language, executive function and social cognition), and with clinical features indicative of AD, identified with the Montreal Cognitive Assessment (MoCA) score range from 22 to 26; (2) no interference with independence in everyday activities; (3) and no better explanation by other psychiatric disorders. NCD-AD patients fulfill the criteria of NCD and have impaired episodic memory assessed by delayed recall.
- Sleep disturbances are defined as a Pittsburgh Sleep Quality Index (PSQI) total score above 5.
Who cannot join
- Previous diagnosis of other major neurocognitive disorders;
- Past history of bipolar disorders or psychosis;
- Physically frail affecting attendance to training sessions;
- Already attending regular training, such as cognitive behavioral therapy;
- Taking a psychotropic or other medication known to affect cognition (e.g. anti-dementia medication);
- Significant communicative impairments.
- History of major neurological deficit including stroke, transient ischemic attack or brain tumor.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Gamma-band High-definition Transcranial Alternating Current Stimulation (HD-tACS) for Sleep Disturbances in Mild Neurocognitive Disorders Due to Alzheimer's Disease
Background: Sleep disturbances are highly prevalent in ageing population and patients with age-related neurodegenerative diseases, which severely affect cognition and even lead to accumulated amyloid-β (Aβ). At present, non-pharmacological interventions for sleep disturbances in dementia patients are accepted as first line of treatment, of which the evidence from clinical trials is very limited. Encouraging results from recent studies on transcranial direct current stimulation (tDCS) showed moderate positive effects on sleep quality in preclinical Alzheimer's disease (AD). Compared to tDCS, high-definition transcranial alternating current stimulation (HD-tACS) enables the entrainment of neuronal activities with optimized focality through injecting small electric current with a specific frequency and has significant enhancement effects on slow wave activities.
Objectives: The investigators aim to 1) investigate and compare the safety, efficacy and sustainability of 40 Hz HD-tACS and HD-tDCS over left dorsolateral prefrontal cortex (DLPFC) in mild neurocognitive disorder due to AD (NCD-AD) patients with sleep disturbances; 2) examine the relationship between the changes in sleep quality, cognitive function and saliva Aβ levels.
Read more
Methods: Chinese right-handed mild NCD-AD patients with sleep disturbances (aged from 60 to 90 years) will be randomly assigned to a 4-week intervention of either HD-tACS, HD-tDCS, or sham HD-tCS, with 33 participants per arm. Before intervention, structural magnetic resonance imaging (MRI) data is used to construct individual realistic head model. Comprehensive assessments, including sleep quality, cognitive performance and saliva Aβ levels will be conducted at baseline, 4th week, 8th week, 12th week and 24th week. Program adherence and adverse effects will be monitored throughout intervention.
Data analysis: The primary outcomes will be the changes in sleep quality and memory performance with modality-driven paradigms (HD-tACS, HD-tDCS, sham HD-tCS), and comparisons of group differences across different time points. Secondary outcomes will be the changes objective sleep pattern, global cognition, saliva Aβ levels and quality of life. 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.
Significance: This study aims to investigate the feasibility, safety and efficacy of HD-tACS and HD-tDCS over left DLPFC for sleep disturbances and cognitive dysfunction in mild NCD-AD patients. It wills also test the program adherence, tolerability and adverse effects of this innovative neurotechonology. Information will be helpful for in-depth understanding the relationship of "sleep disturbances-amyloid deposition" and guiding the further studies of sleep medicine and neurodegenerative diseases.
- Conditions
- Brain Stimulation, Alzheimer Disease, tACS, Sleep Disturbance, Aging, Cognitive Impairment, Mild
- Being tested
- High-definition transcranial current stimulation
- Medical subject headings
- Alzheimer Disease, Parasomnias, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-definition transcranial current stimulationDevice
High-definition transcranial current stimulation (HD-tCS) is delivered by a battery driven direct current stimulator (DC-Stimulator Plus, NeuroConn, Ilmenau, Germany) through a central anodal electrode surrounded by four return cathodal electrodes.
| Study group | Role | What they receive |
|---|---|---|
| 40 Hz HD-tACS | Experimental | The stimulation parameters of HD-tACS include: 20 minutes at 40 Hz, 2 milliamps. Receives: Device: High-definition transcranial current stimulation |
| HD-tDCS | Active comparator | The stimulation parameters of HD-tDCS include: 20 minutes at 2 milliamps, 20 seconds fade-in and 20 seconds fade-out. Receives: Device: High-definition transcranial current stimulation |
| Sham HD-tCS | Sham comparator | In sham condition, the stimulation only last for 30 seconds with the electrodes left in place for a further 20 minutes. This procedure mimics the transient skin sensation of tingling induced by active HD-tACS and HD-tDCS without producing any sustainable effects. Receives: Device: High-definition transcranial current stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pittsburg Sleep Quality Index (PSQI)
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 (Buysse et al., 1988). 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%)(Buysse et al., 1988). Greater score of PSQI indicates worse sleep quality.
Measured: 24 weeks
Delayed recall of words
Word-list learning test (WLLT), consisting of sixteen semantically non-associated words, is presented consecutively over three free trials of immediate recall, a 20-min delayed recall (to prevent recency effects) (Lu et al., 2018). The raw numbers of words recalled are used to assess the memory function.
Measured: 24 weeks
Secondary outcomes (3)
Efficacy evaluated by attention function performance
Attention network function measured by computerized attention network test (ANT)
Measured: 24 weeks
Efficacy evaluated by executive function performance
Executive function is measured by category verbal fluency test (CVFT).
Measured: 24 weeks
Efficacy evaluated by saliva Aβ40 and Aβ42 levels
The levels of Aβ40 and Aβ42 in the saliva samples will be quantified by enzyme-linked immunosorbent assay (ELISA)-type assays (Aurin Biotech, Inc.).
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2022
- Study start1 Oct 2022
- Primary completion30 Dec 2023
- Study completion28 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain StimulationStudies 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
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, LU Hanna, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05544201
- Sponsor's protocol ID
- RGC14111021
- Status last verified
- Mar 2024
- First submitted
- 14 Sep 2022
- Last updated
- 18 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Lu H, Li J, Yang NS, Lam LCW, Ma SL, Wing YK, Zhang L. Using gamma-band transcranial alternating current stimulation (tACS) to improve sleep quality and cognition in patients with mild neurocognitive disorders due to Alzheimer's disease: A study protocol for a randomized controlled trial. PLoS One. 2023 Aug 4;18(8):e0289591. doi: 10.1371/journal.pone.0289591. eCollection 2023.
PubMed 37540692
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gamma-band High-definition Transcranial Alternating Current Stimulation (HD-tACS) for Sleep Disturbances in Mild Neurocognitive Disorders Due to Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT05544201
- Acronym / sponsor ID
- RGC14111021
- Conditions
- Brain Stimulation, Alzheimer Disease, tACS, Sleep Disturbance, Aging, Cognitive Impairment, Mild
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- 1 Oct 2022 (actual)
- Primary completion
- 30 Dec 2023 (actual)
- Study completion
- 28 Feb 2024 (actual)
- First posted
- 16 Sep 2022 (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 are highly prevalent in ageing population and patients with age-related neurodegenerative diseases, which severely affect cognition and even lead to accumulated amyloid-β (Aβ). At present, non-pharmacological interventions for sleep disturbances in dementia patients are accepted as first line of treatment, of which the evidence from clinical trials is very limited. Encouraging results from recent studies on transcranial direct current stimulation (tDCS) showed moderate positive effects on sleep quality in preclinical Alzheimer's disease (AD). Compared to tDCS, high-definition transcranial alternating current stimulation (HD-tACS) enables the entrainment of neuronal activities with optimized focality through injecting small electric current with a specific frequency and has significant enhancement effects on slow wave activities.
Objectives: The investigators aim to 1) investigate and compare the safety, efficacy and sustainability of 40 Hz HD-tACS and HD-tDCS over left dorsolateral prefrontal cortex (DLPFC) in mild neurocognitive disorder due to AD (NCD-AD) patients with sleep disturbances; 2) examine the relationship between the changes in sleep quality, cognitive function and saliva Aβ levels.
Methods: Chinese right-handed mild NCD-AD patients with sleep disturbances (aged from 60 to 90 years) will be randomly assigned to a 4-week intervention of either HD-tACS, HD-tDCS, or sham HD-tCS, with 33 participants per arm. Before intervention, structural magnetic resonance imaging (MRI) data is used to construct individual realistic head model. Comprehensive assessments, including sleep quality, cognitive performance and saliva Aβ levels will be conducted at baseline, 4th week, 8th week, 12th week and 24th week. Program adherence and adverse effects will be monitored throughout intervention.
Data analysis: The primary outcomes will be the changes in sleep quality and memory performance with modality-driven paradigms (HD-tACS, HD-tDCS, sham HD-tCS), and comparisons of group differences across different time points. Secondary outcomes will be the changes objective sleep pattern, global cognition, saliva Aβ levels and quality of life. 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.
Significance: This study aims to investigate the feasibility, safety and efficacy of HD-tACS and HD-tDCS over left DLPFC for sleep disturbances and cognitive dysfunction in mild NCD-AD patients. It wills also test the program adherence, tolerability and adverse effects of this innovative neurotechonology. Information will be helpful for in-depth understanding the relationship of "sleep disturbances-amyloid deposition" and guiding the further studies of sleep medicine and neurodegenerative diseases.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 40 Hz HD-tACS | Experimental | Device: High-definition transcranial current stimulationThe stimulation parameters of HD-tACS include: 20 minutes at 40 Hz, 2 milliamps. |
| HD-tDCS | Active comparator | Device: High-definition transcranial current stimulationThe stimulation parameters of HD-tDCS include: 20 minutes at 2 milliamps, 20 seconds fade-in and 20 seconds fade-out. |
| Sham HD-tCS | Sham comparator | Device: High-definition transcranial current stimulationIn sham condition, the stimulation only last for 30 seconds with the electrodes left in place for a further 20 minutes. This procedure mimics the transient skin sensation of tingling induced by active HD-tACS and HD-tDCS without producing any sustainable effects. |
Who may qualify
- Ages
- 60 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Chinese, aged from 60 to 90 years.
- Mild neurocognitive disorder due to Alzheimer's disease (NCD-AD) is diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). NCD-AD patients are defined by the following criteria: (1) evidence of modest cognitive decline in at least one of six domains of cognition (memory, perceptual- motor, complex attention, language, executive function and social cognition), and with clinical features indicative of AD, identified with the Montreal Cognitive Assessment (MoCA) score range from 22 to 26; (2) no interference with independence in everyday activities; (3) and no better explanation by other psychiatric disorders. NCD-AD patients fulfill the criteria of NCD and have impaired episodic memory assessed by delayed recall.
- Sleep disturbances are defined as a Pittsburgh Sleep Quality Index (PSQI) total score above 5.
Key exclusion criteria (7 listed)
- Previous diagnosis of other major neurocognitive disorders;
- Past history of bipolar disorders or psychosis;
- Physically frail affecting attendance to training sessions;
- Already attending regular training, such as cognitive behavioral therapy;
- Taking a psychotropic or other medication known to affect cognition (e.g. anti-dementia medication);
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 |
|---|---|---|
| High-definition transcranial current stimulationHigh-definition transcranial current stimulation (HD-tCS) is delivered by a battery driven direct current stimulator (DC-Stimulator Plus, NeuroConn, Ilmenau, Germany) through a central anodal electrode surrounded by four return cathodal electrodes. | Device | 40 Hz HD-tACS, HD-tDCS, Sham HD-tCS |
Primary outcome
Pittsburg Sleep Quality Index (PSQI)
Time frame: 24 weeks
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 (Buysse et al., 1988). 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%)(Buysse et al., 1988). Greater score of PSQI indicates worse sleep quality.
Delayed recall of words
Time frame: 24 weeks
Word-list learning test (WLLT), consisting of sixteen semantically non-associated words, is presented consecutively over three free trials of immediate recall, a 20-min delayed recall (to prevent recency effects) (Lu et al., 2018). The raw numbers of words recalled are used to assess the memory function.
3 secondary outcomes
Efficacy evaluated by attention function performance
Time frame: 24 weeks
Efficacy evaluated by executive function performance
Time frame: 24 weeks
Efficacy evaluated by saliva Aβ40 and Aβ42 levels
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2024.
- Derived from this study: PubMed 37540692Lu H, Li J, Yang NS, Lam LCW, Ma SL, Wing YK, Zhang L. Using gamma-band transcranial alternating current stimulation (tACS) to improve sleep quality and cognition in patients with mild neurocognitive disorders due to Alzheimer's disease: A study protocol for a randomized controlled trial. PLoS One. 2023 Aug 4;18(8):e0289591. doi: 10.1371/journal.pone.0289591. eCollection 2023.
- Individual participant dataSharing planned: Undecided
Related trials for Brain Stimulation
Not yet recruiting
Temporal Interference Stimulation for Upper-Limb Motor Recovery in Early Subacute Stroke
Acute Ischemic Stroke
Recruiting
Additional Effects on tDCS With AOT on Lower Limb Functions on Children With Diplegic CP
Diplegic Cerebral Palsy
Active, not recruiting
Improving Visual Field Deficits With Noninvasive Brain Stimulation
Visual Field Defect, Peripheral, Stroke
Not yet recruiting
Deep Brain Stimulation for Treatment-Resistant Schizophrenia
Treatment Resistant Disorders
Recruiting
Temporal Interference Methods for Non-invasive Deep Brain Stimulation, Study 1.3
Healthy Volunteers
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.
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 High-definition transcranial current stimulation in people with Brain Stimulation and Alzheimer Disease, 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 3 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: finished, as of the sponsor's last update on 18 Mar 2024. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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: 24 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?
On the ClinicalTrials.gov record for NCT05544201, which also lists 1 linked publication.
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 18 Mar 2024.