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Status unknownNCT06346015GES-aSAHUpdated Apr 3, 2024

Gamma Entrainment Stimulation for Cognitive Dysfunction After aSAH

An interventional study of Gamma Entrainment Stimulation in Subarachnoid Hemorrhage, Aneurysmal and Cognitive Dysfunction, sponsored by Beijing Tiantan Hospital. Status unknown. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-04-03.

Sponsored by Beijing Tiantan Hospital · Not applicable, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Mar 2024), so the status shown — last known as Not yet recruiting — may be out of date.
Phase
Not applicable
Study type
Interventional
Enrollment
60
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
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Study summary

The goal of this clinical trial is to Explore and verify whether 40Hz audio and binaural beat 40Hz audio can improve the postoperative cognitive dysfunction seen in patients with aneurysmal subarachnoid hemorrhage. This study is a single-center, prospective, randomized, controlled clinical trial. Patients with aneurysmal subarachnoid hemorrhage were selected and randomized into intervention group (audio adjuvant group) and control group (conventional treatment group). Patients in the intervention group will receive audio therapy after surgery, and patients in the control group will receive usual care. EEG, fMRI and mRS scores were evaluated after 3 months of follow-up.

Read the detailed description

Aneurysmal subarachnoid hemorrhage (aSAH) is a neurological malady that has garnered global public health apprehension due to its severity. Research indicates that cerebral ischemic events subsequent to aSAH treatment are both pervasive and intricate, with their occurrence mechanism and timing categorized into early and late onset. Early cerebral ischemia typically manifests within 1-3 days post-aSAH onset, primarily attributed to factors such as cerebral vasospasm, hemorrhagic cerebral edema, and thrombosis. The severity of these lesions can be alleviated through medical, endovascular, and surgical interventions. Conversely, delayed cerebral ischemia generally arises between 4 days to 2 weeks after surgery, predominantly stemming from cerebral edema, inflammatory reactions, cortical depolarization, and microthrombosis. Managing delayed cerebral ischemia necessitates vigilant patient monitoring and the maintenance of stable cerebral blood flow, achieved by mitigating the impact of cerebral edema and inflammatory responses. Cerebral ischemia induces physiological changes like nerve cell damage, apoptosis, glial cell proliferation, and inflammatory responses, potentially impacting brain function, particularly cognitive function. Consequently, the application of our established TAPS prognostic model effectively identifies individuals at a higher risk of cognitive dysfunction and poor prognosis, facilitating the screening of potential intervention candidates for this study.

In recent years, the scientific community has discerned the pivotal role of microglia in preserving the stability of the brain environment. By modulating their activities, the degree of ischemia can be effectively controlled, mitigating subsequent impairments in brain function. This revelation forms the basis for pioneering nonpharmacological treatment strategies. Among these innovative approaches, frequency-specific audio therapy, notably utilizing 40Hz audio and binaural beat audio, has garnered significant attention. 40Hz audio induces gamma waves in the brain, linked to cognitive functions such as attention, memory, and perception. Binaural beat audio, a neuroacoustic phenomenon, involves introducing two sounds with slightly different frequencies to the ears, prompting the brain to create a new EEG frequency. Regarding 40Hz audio, its potential efficacy is closely tied to the induction of gamma waves, associated with heightened focus and information processing. Laboratory studies suggest that playing 40Hz audio stimulates the brain to produce more gamma waves, hinting at its potential to enhance human cognitive function by regulating electrical brain activity. Binaural beat audio operates on a more intricate level. The brain attempts to "synchronize" two audio pieces with slightly different frequencies, generating a new EEG frequency. This neuroacoustic phenomenon induces specific brain activity, potentially enhancing cognitive function. Crucially, whether 40Hz audio or binaural beat audio, their efficacy may hinge on the "neuroplasticity" of the brain, signifying the brain's ability to alter its structure and function in response to sustained external stimulation. This "frequency-following response" induced by audio stimuli may bring about neuroplasticity changes, further enhancing cognitive function.

For specific brain disorders like Alzheimer's disease, audio therapy could prove impactful. In Alzheimer's patients, gamma-wave activity in the brain is typically diminished, but preliminary studies indicate that 40Hz audio stimulation may enhance gamma activity, potentially improving memory and attention. Moreover, binaural beat audio may contribute to enhancing mental and physical well-being. Research suggests that it can modify the brain's electrical activity pattern, improving emotional states, reducing anxiety and stress, and enhancing sleep quality.

In conclusion, both 40Hz audio and binaural beat audio, as potential non-pharmacological therapeutic strategies, warrant widespread attention from the research community. Although the current study is in its early stages, if audio therapy effectively ameliorates the cognitive dysfunction resulting from aneurysmal subarachnoid hemorrhage, it could introduce novel possibilities for the rehabilitation of this condition.

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Conditions studied

  • Subarachnoid Hemorrhage, Aneurysmal
  • Cognitive Dysfunction
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In context

Subarachnoid Hemorrhage

521 studies on the registry are indexed under Subarachnoid Hemorrhage; 126 are open to participants now.

This study's planned enrollment of 60 is close to the median of 56 across 267 interventional studies indexed under Subarachnoid Hemorrhage.

Browse Subarachnoid Hemorrhage studies →

Lead sponsor

Beijing Tiantan Hospital is the lead sponsor of 481 studies on the registry; 287 are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Diagnosis of aneurysmal subarachnoid hemorrhage and aneurysm secured
  2. Postoperative TAPS score ≥ 2 points
  3. Age: 18 years old and 75 years old
  4. Hearing function is not impaired and audio therapy is well tolerated
  5. informed Consented

Exclusion criteria

Exclusion Criteria:

  1. Hearing impairment or significant discomfort with audio therapy
  2. In other clinical trials within three months before the trial
  3. Pregnant women and lactating women
  4. Drugs that may affect cognitive function should be used during the study
  5. Previous history including cognitive dysfunction or mental illness
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Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
60 participants (estimated)

Study arms

  • Experimental
    Gamma Entrainment Stimulation + Standard Care

    Gamma Entrainment Stimulation

    Procedure: Gamma Entrainment Stimulation

  • No intervention
    Standard Care

Interventions

  • ProcedureGamma Entrainment Stimulation

    Audio-assisted therapy: receive audio therapy with a specific device for 30 minutes, once in the morning and evening for 3 months. (Binaural beat treatment group: receive binaural beat treatment with a specific device for 30 minutes, once in the morning and evening, for 3 months.)

    Also known as: Audio-assistied therapy

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What researchers measure

Primary outcomes

  1. Montreal Cognitive Assessment (MoCA) scores < 22

    Time frame: at 3 months after enrollment

  2. mini-mental state examiniation (MMSE) < 27

    Time frame: at 3 months after enrollment

  3. modified Rankin Scales (mRS) > 2

    unfavorable outcome

    Time frame: at 3 months after enrollment

Secondary outcomes

  1. electroencephalogram (EEG) indicators

    auditory steady state evoked response (ASSR) P(50), N(100) and P(200) components Frequency following responses (FFRs) EEG frequency ranges of alpha, beta, delta, theta and gamma

    Time frame: at 3 months after enrollment

  2. functional Magnetic Resonance Imaging (fMRI) indicators

    ALFF: Amplitude of Low Frequency Fluctuation fALFF: fractional Amplitude of Low Frequency Fluctuation ReHo: Regional Homogeneity FC: Functional Connectivity VMHC: Voxel-Mirrored Homotopic Connectivity FCD: Functional Connectivity Density

    Time frame: at 3 months after enrollment

Other outcomes

  1. Safety indicator

    the occurrence of serious adverse events. Including, but not limited to, serious physical or psychological reactions, serious complications or other health problems. All adverse events and serious adverse events will be recorded in detail, including the nature of the event, time to start and end, severity, association with study treatment, management measures, and outcome.

    Time frame: at 3 months after enrollment

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Study locations

No study locations are listed for this record.

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References and documents

Publications

  • 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. PubMed 27929004 ↗
  • Martorell AJ, Paulson AL, Suk HJ, Abdurrob F, Drummond GT, Guan W, Young JZ, Kim DN, Kritskiy O, Barker SJ, Mangena V, Prince SM, Brown EN, Chung K, Boyden ES, Singer AC, Tsai LH. Multi-sensory Gamma Stimulation Ameliorates Alzheimer's-Associated Pathology and Improves Cognition. Cell. 2019 Apr 4;177(2):256-271.e22. doi: 10.1016/j.cell.2019.02.014. Epub 2019 Mar 14. PubMed 30879788 ↗
  • Adaikkan C, Middleton SJ, Marco A, Pao PC, Mathys H, Kim DN, Gao F, Young JZ, Suk HJ, Boyden ES, McHugh TJ, Tsai LH. Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection. Neuron. 2019 Jun 5;102(5):929-943.e8. doi: 10.1016/j.neuron.2019.04.011. Epub 2019 May 7. PubMed 31076275 ↗
  • Chen X, Shi X, Wu Y, Zhou Z, Chen S, Han Y, Shan C. Gamma oscillations and application of 40-Hz audiovisual stimulation to improve brain function. Brain Behav. 2022 Dec;12(12):e2811. doi: 10.1002/brb3.2811. Epub 2022 Nov 14. PubMed 36374520 ↗

Individual participant data

Plan to share: Undecided

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 3, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT06346015
Collaborators
Shanghai Joyingmed Sensory Stimulation Lab
Responsible party
Xiaolin Chen, MD (Director, Beijing Tiantan Hospital) — Principal investigator
First posted
Apr 3, 2024
Start date
Apr 1, 2024 (estimated)
Primary completion
Mar 31, 2025 (estimated)
Completion
Mar 31, 2025 (estimated)
Last update
Apr 3, 2024

Study contacts

Fa Lin, MD
Contact
13681107240@163.com
13681107240
Runting Li, MD
Contact
tt18080lrt@163.com
Guangzhi Shi, MD
study director · Beijing Tiantan Hospital
Jun Yang, MD
study director · Beijing Tiantan Hospital
Yu Chen, MD
study director · Beijing Tiantan Hospital
Ke Wang, MD
study director · Beijing Tiantan Hospital
Cunyang Li, MD
study director · Beijing Tiantan Hospital
Junwei Lv, MD
study director · Shanghai Joyingmed Sensory Stimulation Lab
Nianze Chen, MD
study director · Shanghai Joyingmed Sensory Stimulation Lab

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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