40 Hz Audio-Visual Stimulation Therapy for AD
A Clinical Trial Assessing the Efficacy of 40 Hz Auditory-Visual Stimulation for Patients With Alzheimer's Disease
This is a single-center, parallel-group, double-blind randomized controlled trial conducted at the First Affiliated Hospital of Xiamen University, enrolling 50 participants with Alzheimer's disease (AD)-derived mild cognitive impairment (MCI) or mild AD aged 50-80 years with ≥4 years of education. Subjects must meet diagnostic criteria per Chinese AD guidelines, show medial temporal lobe atrophy on baseline brain MRI, have a reliable caregiver, and be capable of completing all assessments. Exclusion criteria include severe visual/auditory impairment, non-AD dementia, recent neuromodulation therapy, uncontrolled severe systemic diseases, prominent psychiatric disorders, significant cerebral focal lesions on MRI, and other conditions precluding safe participation.
Eligible participants will be randomly assigned to either the 40 Hz audio-visual stimulation group or the placebo group. The intervention lasts 1 hour once daily for 12 weeks, with a total subject follow-up period of 36 weeks (12-week treatment + 24-week observational follow-up). The primary efficacy outcome is the change from baseline in the 11-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) at the end of treatment. Secondary outcomes include changes in Mini-Mental State Examination (MMSE) and ADCS-Activities of Daily Living (ADCS-ADL) scores across all follow-up visits. Exploratory biomarkers cover plasma Aβ42, Aβ40, Tau-217, gamma wave power on electroencephalography (EEG), and repeat Aβ-PET imaging (if previously performed). Cognitive, functional, emotional, EEG, and blood biomarker assessments will be conducted at scheduled time points. Safety monitoring focuses on intervention-related adverse events such as headache and dizziness, with detailed recording of onset, duration and accompanying symptoms.
Statistical analyses will use two-sided tests at α=0.05. Linear mixed models and repeated-measures ANOVA with ANCOVA adjustment for covariates will analyze the primary endpoint; appropriate parametric or nonparametric tests will be applied for secondary and exploratory outcomes. Baseline group balance will be compared via t-tests, Mann-Whitney U tests or chi-square tests. All data processing and statistical modeling will be performed using Python 3.11 and related analytical packages. The trial runs from July 2026 to December 2027.
Přehled studie
Postavení
Typ studie
Zápis (Odhadovaný)
Fáze
- Nelze použít
Kontakty a umístění
Studijní kontakt
- Jméno: Ping Zhong, phd
- Telefonní číslo: 15280805698
- E-mail: jgszp2004@163.com
Studijní místa
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Fujian
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Xiamen, Fujian, Čína, 361003
- The First Affiliated Hospital of Xiamen University
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Kontakt:
- Neurosurgery department
- Telefonní číslo: 15280805698
- E-mail: jgszp2004@163.com
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria Subjects diagnosed with Alzheimer's disease-derived mild cognitive impairment (AD-MCI) or mild Alzheimer's dementia, diagnosed in accordance with Chinese Guidelines for the Diagnosis and Treatment of Alzheimer's Dementia (2020 Edition) and Chinese Expert Consensus on the Diagnosis and Treatment of AD-derived Mild Cognitive Impairment (2021).
Clinical Dementia Rating sum of boxes (CDR-SB) score ranges from 0.5 to 1. Age between 50 and 80 years old, with education ≥ 4 years, any biological sex. Able to cooperate with 12-week intervention and all scheduled assessments including cognitive scales, EEG, blood tests and brain imaging.
Subject or legal guardian provides written informed consent and agrees to comply with study procedures.
Baseline brain MRI with coronal hippocampal sequence shows medial temporal lobe atrophy (MTA) grade ≥2, highly suggestive of AD pathology.
Has a stable, reliable caregiver throughout the study period. Exclusion Criteria Severe visual impairment (uncorrected visual acuity <0.1, unable to detect flickering light) or severe hearing loss (pure tone audiometry ≥60 dB, cannot perceive 40 Hz auditory stimulation).
Cognitive decline caused by non-AD etiologies: vascular dementia, mixed dementia, dementia with Lewy bodies, Parkinson's disease dementia, frontotemporal dementia, Huntington's disease, cognitive impairment secondary to thyroid disorders, vitamin B12/folate deficiency, or other organic brain diseases.
Received other neuromodulation therapies (TMS, tDCS, etc.) within 3 months prior to screening or participated in other interventional cognitive trials recently.
Uncontrolled severe systemic diseases: advanced heart failure, arrhythmia, refractory hypertension, severe hepatic/renal dysfunction, active malignant tumors.
History of schizophrenia, mania or other severe psychiatric disorders; GDS ≥15 or HAMA ≥14 at screening; receiving antidepressant, anxiolytic or antipsychotic medication at screening.
Hachinski Ischemic Score (HIS) >4. Baseline MRI shows significant focal cerebral lesions: ≥2 infarcts >2 cm; infarcts in thalamus, hippocampus, entorhinal cortex or angular gyrus; Fazekas white matter hyperintensity grade ≥3.
Active HIV, syphilis, hepatitis B/C or other severe chronic infectious diseases.
Severe communication disorders or altered consciousness preventing completion of assessments or intervention.
Refusal of informed consent by legal guardian. Any other clinical condition judged by investigators to make the subject unsuitable for participation.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Čtyřnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: 40 Hz Audio-Visual Stimulation Experimental Group
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Non-invasive audio-visual neuromodulation device generating synchronized 40 Hz light flicker and sound stimulation. Subjects receive 1 session daily, 1 hour per session, for a total of 12 consecutive weeks. After intervention, 24 weeks of observational follow-up without stimulation is performed. |
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Komparátor placeba: Sham Audio-Visual Stimulation Placebo Control Group
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Identical external device appearance with non-therapeutic low-frequency light and sound signals without 40 Hz gamma oscillation. Administration frequency, duration and operation process are completely consistent with the experimental group, once daily for 1 hour over 12 weeks, followed by 24 weeks of off-treatment follow-up. |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Časové okno |
|---|---|
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Change from baseline in the 11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) total score at Week 12 (end of intervention)
Časové okno: Baseline and Week 12 (12 weeks after randomization)
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Baseline and Week 12 (12 weeks after randomization)
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Sekundární výstupní opatření
Měření výsledku |
Časové okno |
|---|---|
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Change from baseline in ADCS-Activities of Daily Living (ADCS-ADL) total score
Časové okno: Baseline, Week 12, Week 36
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Baseline, Week 12, Week 36
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Další výstupní opatření
Měření výsledku |
Časové okno |
|---|---|
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Changes in plasma Aβ42, Aβ40 and Tau-217 levels from baseline
Časové okno: Baseline, Week 12
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Baseline, Week 12
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Changes on Aβ-PET imaging (if baseline Aβ-PET was performed)
Časové okno: Baseline, Week 12 (only for subjects with baseline Aβ-PET scan)
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Baseline, Week 12 (only for subjects with baseline Aβ-PET scan)
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Changes in electroencephalography (EEG) gamma wave power from baseline
Časové okno: Baseline, Week 12, Week 36
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Baseline, Week 12, Week 36
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Spolupracovníci a vyšetřovatelé
Publikace a užitečné odkazy
Obecné publikace
- Jones M, McDermott B, Oliveira BL, O'Brien A, Coogan D, Lang M, Moriarty N, Dowd E, Quinlan L, Mc Ginley B, Dunne E, Newell D, Porter E, Elahi MA, O' Halloran M, Shahzad A. Gamma Band Light Stimulation in Human Case Studies: Groundwork for Potential Alzheimer's Disease Treatment. J Alzheimers Dis. 2019;70(1):171-185. doi: 10.3233/JAD-190299.
- Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, Gillingham TZ, Mathys H, Seo J, Kritskiy O, Abdurrob F, Adaikkan C, Canter RG, Rueda R, Brown EN, Boyden ES, Tsai LH. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 2016 Dec 7;540(7632):230-235. doi: 10.1038/nature20587.
- Chan D, Suk HJ, Jackson BL, Milman NP, Stark D, Klerman EB, Kitchener E, Fernandez Avalos VS, de Weck G, Banerjee A, Beach SD, Blanchard J, Stearns C, Boes AD, Uitermarkt B, Gander P, Howard M 3rd, Sternberg EJ, Nieto-Castanon A, Anteraper S, Whitfield-Gabrieli S, Brown EN, Boyden ES, Dickerson BC, Tsai LH. Gamma frequency sensory stimulation in mild probable Alzheimer's dementia patients: Results of feasibility and pilot studies. PLoS One. 2022 Dec 1;17(12):e0278412. doi: 10.1371/journal.pone.0278412. eCollection 2022.
- Da X, Hempel E, Ou Y, Rowe OE, Malchano Z, Hajos M, Kern R, Megerian JT, Cimenser A. Noninvasive Gamma Sensory Stimulation May Reduce White Matter and Myelin Loss in Alzheimer's Disease. J Alzheimers Dis. 2024;97(1):359-372. doi: 10.3233/JAD-230506.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
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