NCT05544201

Transcranial Alternating Current Stimulation (TACS) for Sleep Disturbances in Neurocognitive Disorders Due to Alzheimer's Disease

Completed NA Last updated 18 March 2024

What this trial tests

NA trial testing High-definition transcranial current stimulation in Brain Stimulation in 99 participants. Completed in 28 February 2024.

Timeline

1 October 2022

Primary endpoint
30 December 2023

28 February 2024

Quick facts

Lead sponsor	Chinese University of Hong Kong
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	factorial
Masking	double
Primary purpose	treatment
Enrollment	99
Start date	1 October 2022
Primary completion	30 December 2023
Estimated completion	28 February 2024
Sites	1 location across Hong Kong

Drugs / interventions tested

• High-definition transcranial current stimulation

Conditions studied

• Brain Stimulation — all drugs for Brain Stimulation →
• Alzheimer Disease — all drugs for Alzheimer Disease →
• tACS — all drugs for tACS →
• Sleep Disturbance — all drugs for Sleep Disturbance →

Sponsor

Chinese University of Hong Kong

Who can join

Adults 60 to 90, any sex, with Brain Stimulation or Alzheimer Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Audiovisual gamma stimulation for the treatment of neurodegeneration.
   Blanco-Duque C, Chan D, Kahn MC, Murdock MH, et al · · 2024 · cited 42× · PMID 38115692 · DOI 10.1111/joim.13755
2. Proteostasis failure exacerbates neuronal circuit dysfunction and sleep impairments in Alzheimer's disease.
   Morrone CD, Raghuraman R, Hussaini SA, Yu WH. · · 2023 · cited 40× · PMID 37085942 · DOI 10.1186/s13024-023-00617-4
3. Transcranial alternating current stimulation (tACS) at gamma frequency: an up-and-coming tool to modify the progression of Alzheimer's Disease.
   De Paolis ML, Paoletti I, Zaccone C, Capone F, et al · · 2024 · cited 17× · PMID 38926897 · DOI 10.1186/s40035-024-00423-y
4. Transcranial alternating current stimulation for neuropsychiatric disorders: a systematic review of treatment parameters and outcomes.
   Gholamali Nezhad F, Martin J, Tassone VK, Swiderski A, et al · · 2024 · cited 7× · PMID 39211537 · DOI 10.3389/fpsyt.2024.1419243
5. 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.
   Lu H, Li J, Yang NS, Lam LCW, et al · · 2023 · cited 5× · PMID 37540692 · DOI 10.1371/journal.pone.0289591
6. Daily high-frequency transcranial random noise stimulation (hf-tRNS) for sleep disturbances and cognitive dysfunction in patients with mild vascular cognitive impairments: A study protocol for a pilot randomized controlled trial.
   Gong Y, Li J, Yuen YS, Yang NS, et al · · 2024 · cited 2× · PMID 39441802 · DOI 10.1371/journal.pone.0309233
7. The Potential for Neuromodulation in the Treatment of Alzheimer's Disease: A Review of Clinical Trials.
   Jones T, Shalom M, Chalamgari A, Gold J, et al · · 2025 · PMID 40599507 · DOI 10.7759/cureus.85156