At Home Gamma tACS in Alzheimer's Disease (tACS@Home)

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Status: Completed

Conditions: Alzheimer Disease

Treatments: Device: 40 Hz transcranial alternating current stimulation; Device: Sham stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT05643326

NP5395

Details and patient eligibility

About

Brain oscillations are ubiquitous in the human brain and have been implicated in cognitive and behavioral states defined in precisely tuned neural networks. In neurodegenerative disorders, neurodegeneration is accompanied by changes in oscillatory activity leading to the emerging concept of neurological and psychiatric disorders as "oscillopathies". Alzheimer's disease, which accounts for the vast majority of age-related dementias, is characterised by a prominent disruption of oscillations in the gamma frequency band. The restoration of gamma oscillations by neural entrainment in animal models of Alzheimer's disease have shown a remarkable decrease in the pathological burden of amyloid and tau via increased microglial activity, resulting in a significant increase of cognitive performances.

Transcranial alternating current brain stimulation (tACS), is a neurophysiological method of non-invasive modulation of the excitability of the central nervous system that is having an increasingly numerous spectrum of potential therapeutic applications. Recent studies have demonstrated the effectiveness of this method in modulating the natural frequencies of cerebral oscillation, underlying multiple cognitive processes such as verbal memory, perception and working memory.

On the basis of these premises, the treatment with gamma tACS is proposed in patients affected by Alzheimer's disease.

In this randomized, double-blind, sham-controlled study, followed by an open-label phase, the investigators will evaluate whether a 9- or 18-weeks treatment with gamma tACS over the precuneus, delivered at home, can improve symptoms in patients with mild Alzheimer's disease.

Full description

Brain oscillations are ubiquitous in the human brain and have been implicated in cognitive and behavioral states defined in precisely tuned neural networks. In neurodegenerative disorders, neurodegeneration is accompanied by changes in oscillatory activity leading to the emerging concept of neurological and psychiatric disorders as "oscillopathies". Alzheimer's disease, which accounts for the vast majority of age-related dementias, is characterised by a prominent disruption of oscillations in the gamma frequency band. The restoration of gamma oscillations by neural entrainment in animal models of Alzheimer's disease have shown a remarkable decrease in the pathological burden of amyloid and tau via increased microglial activity, resulting in a significant increase of cognitive performances.

Transcranial alternating current brain stimulation (tACS), is a neurophysiological method of non-invasive modulation of the excitability of the central nervous system that is having an increasingly numerous spectrum of potential therapeutic applications. Recent studies have demonstrated the effectiveness of this method in modulating the natural frequencies of cerebral oscillation, underlying multiple cognitive processes such as verbal memory, perception and working memory.

On the basis of these premises, the treatment with gamma tACS is proposed in patients affected by Alzheimer's disease.

In this randomized, double-blind, sham-controlled study, followed by an open-label phase, the investigators will evaluate whether a 9- or 18-weeks treatment with gamma tACS over the precuneus, delivered at home, can improve symptoms in patients with mild Alzheimer's disease.

Subjects will be randomized in two groups in the first part of the trial. One group will receive a two-months treatment with gamma tACS (40 Hz) over the precuneus while the other group will receive placebo (sham) stimulation. After two-months, both group will undergo real stimulation (open-label phase) with gamma tACS (40 Hz) over the precuneus for two-months. Modulators of response will be considered.

Enrollment: 53 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for the Patient:

• Mild Alzheimer's disease (CDR 0.5 - 1)

Exclusion Criteria for the Patient:

• Cerebrovascular disorders
• Previous stroke
• Hydrocephalus
• Intra-cranial mass documented by MRI
• History of traumatic brain injury or other neurological diseases
• Serious medical illness other than AD
• History of seizures
• Pregnancy
• Metal implants in the head (except dental fillings)
• Electronic implants (i.e. pace-maker, implanted medical pump)
• Age <18 years

Inclusion Criteria for the Caregiver:

• Age > 18 years
• Compliance in participation in training on the use of the therapeutic device
• Mini-Mental State Examination >26/30

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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53 participants in 2 patient groups

Real tACS - Real tACS

Experimental group

Description:

42 sessions of 40 Hz transcranial alternating current stimulation (5 days/week for 9 weeks) followed by an open-label 42 sessions of 40 Hz transcranial alternating current stimulation (5 days/week for 9 weeks).

Treatment:

Device: 40 Hz transcranial alternating current stimulation

Sham tACS - Real tACS

Sham Comparator group

Description:

42 sessions of sham stimulation (5 days/week for 9 weeks) followed by an open-label 42 sessions of 40 Hz transcranial alternating current stimulation (5 days/week for 9 weeks).

Treatment:

Device: Sham stimulation

Device: 40 Hz transcranial alternating current stimulation