Alzheimer DiseasetACS@HomeNCT05643326
At Home Gamma tACS in Alzheimer's Disease (tACS@Home)
A study testing 40 Hz transcranial alternating current stimulation in people with Alzheimer Disease, run by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia at 1 site in Italy.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- 40 Hz transcranial alternating current stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 53 participants
- Where
- 1 siteItaly
- Study dates
- 10 Dec 2022to 15 Oct 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Mild Alzheimer's disease (CDR 0.5 - 1)
- Age > 18 years
- Compliance in participation in training on the use of the therapeutic device
- Mini-Mental State Examination >26/30
Who cannot join
- 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
Show all 11Show fewer
- History of seizures
- Pregnancy
- Metal implants in the head (except dental fillings)
- Electronic implants (i.e. pace-maker, implanted medical pump)
- Age <18 years
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Markers of Clinical and Biological Response to Home Delivered Transcranial Alternating Current Stimulation (tACS) in Patients With Alzheimer's Disease
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.
Read more
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.
Read the detailed 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.
- Conditions
- Alzheimer Disease
- Being tested
- 40 Hz transcranial alternating current stimulation, Sham stimulation
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
40 Hz transcranial alternating current stimulationDevice
42 sessions of 40 Hz transcranial alternating current stimulation (5 days/week for 9 weeks)
Sham stimulationDevice
42 sessions of sham stimulation (5 days/week for 9 weeks)
| Study group | Role | What they receive |
|---|---|---|
| Real tACS - Real tACS | Experimental | 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). Receives: Device: 40 Hz transcranial alternating current stimulation |
| Sham tACS - Real tACS | Sham comparator | 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). Receives: Device: 40 Hz transcranial alternating current stimulation; Device: Sham stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of transcranial alternating current stimulation delivered at home
Incidence of Treatment-Emergent Adverse Events as assessed by the incidence of adverse events graded from 1 (mild) to 5 (fatal).
Measured: Through study completion, at week 24
Tolerability of transcranial alternating current stimulation delivered at home
Tolerability will be evaluated with percentage of compliance (number of delivered stimulations divided by number of programmed stimulations times one-hundred). The primary outcome will be reached if compliance will be >90%.
Measured: Through study completion, at week 24
Changes in Clinical Dementia Rating scale (CDR) sum of boxes
CDR-SB scores range from 0 to 18, with higher scores indicating worse cognition and daily function.
Measured: Difference between treatments (real and sham) at week 8
Changes in Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog)13
ADAS-Cog13 scores range from 0 to 85, with higher scores indicating a greater deficit.
Measured: Difference between treatments (real and sham) at week 8
Changes in Face-Name Associative Memory Test (FNAT) scores
The Face-Name Associative Memory Test is a cross-modal associative memory test, it includes 20 face-name pairs. The administration procedure starts with the presentation of 20 faces with each name and participants should read the name underneath the faces and try to learn each face-name pair. After 5 minutes, the faces are shown one by one and participants are asked to recall the associated names from 4 different names. The correct number of pairs recalled is recorded. The score ranges from 0 (worse performance) to 20 (best performance).
Measured: Difference between treatments (real and sham) at week 8
Changes in Alzheimer's Disease Assessment Scale Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
ADCS-ADL scores range from 0 to 78, with lower scores indicating greater functional impairment.
Measured: Difference between treatments (real and sham) at week 8
Secondary outcomes (17)
Changes in Clinical Dementia Rating scale (CDR) sum of boxes
CDR-SB scores range from 0 to 18, with higher scores indicating worse cognition and daily function.
Measured: Change from baseline to week 8 - 16 - 24
Changes in Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog)13
ADAS-Cog13 scores range from 0 to 85, with higher scores indicating a greater deficit.
Measured: Change from baseline to week 8 - 16 - 24
Changes in Rey Auditory Verbal Learning Test scores
Participants are given a list of 15 unrelated words repeated over five different trials and are asked to repeat. Another list of 15 unrelated words are given and the patient must again repeat the original list of 15 words and then again after 30 minutes. The score ranges from 0 (worse performance) to 15 (best performance).
Measured: Change from baseline to week 8 - 16 - 24
Changes in Face-Name Associative Memory Test (FNAT) scores
The Face-Name Associative Memory Test is a cross-modal associative memory test, it includes 20 face-name pairs. The administration procedure starts with the presentation of 20 faces with each name and participants should read the name underneath the faces and try to learn each face-name pair. After 5 minutes, the faces are shown one by one and participants are asked to recall the associated names from 4 different names. The correct number of pairs recalled is recorded. The score ranges from 0 (worse performance) to 20 (best performance).
Measured: Change from baseline to week 8 - 16 - 24
Changes in the Neuropsychiatric Inventory (NPI-Q)
The NPI-Q is designed to be an informant-based interview that assesses neuropsychiatric symptoms of the participant over the previous month. The score ranges from 0 (no symptoms) to 180 (severe symptoms).
Measured: Change from baseline to week 8 - 16 - 24
Changes in Caregiver Burden Inventory (CBI)
The Caregiver Burden Inventory (CBI) includes 24 items and 5 dimensions: Time-dependence, developmental, physical, emotional, and social burden. There are 5 items for each dimension, except for the physical dimension, which has four items. Each item signifies a score between zero (not descriptive) and four (highly descriptive), with a higher score indicating greater care burden. Therefore the total score for time-dependence, developmental, emotional, and social burden range from 0 to 20 except for physical burden where scores range from 0 to 16. The total score ranges from 0 (no burden) to 96 (severe burden).
Measured: Change from baseline to week 8 - 16 - 24
Changes in Alzheimer's Disease Assessment Scale Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
ADCS-ADL scores range from 0 to 78, with lower scores indicating greater functional impairment.
Measured: Change from baseline to week 8 - 16 - 24
Change in SAI measurements
By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of gamma tACS on short latency afferent inhibition (SAI), which is a marker of cholinergic transmission. SAI is expressed as % of the unconditioned motor evoked potential.
Measured: Change from baseline to week 8 - 16 - 24
Change in EEG gamma power
By using electroencephalography (EEG), the investigators will evaluate the change in gamma power.
Measured: Change from baseline to week 8 - 16 - 24
Change in plasma NfL levels
Changes in plasma neurofilament light (NfL) levels (pg/mL) will be evaluated.
Measured: Change from baseline to week 8 - 16 - 24
Change in plasma GFAP levels
Changes in plasma glial fibrillary acidic protein (GFAP) levels (pg/mL) will be evaluated.
Measured: Change from baseline to week 8 - 16 - 24
Change in plasma amyloid beta1-40 levels
Change in plasma amyloid beta1-40 levels (pg/mL) will be evaluated.
Measured: Change from baseline to week 8 - 16 - 24
Change in plasma amyloid beta1-42 levels
Change in plasma amyloid beta1-42 levels (pg/mL) will be evaluated.
Measured: Change from baseline to week 8 - 16 - 24
Change in plasma pTau217
Change in plasma pTau217 levels (pg/mL) will be evaluated.
Measured: Change from baseline to week 8 - 16 - 24
Change in resting state MRI connectivity
Change in resting state magnetic resonance imaging connectivity (default mode network) both static and dynamic.
Measured: Change from baseline to week 8
Change in plasma TMT part B scores
The Trail Making Test Part B consists of 24 circles on a piece of paper, but rather than all of the circles containing numbers, half of the circles have the numbers 1-12 in them and the other half (12) contain the letters A-L. The person taking the test has to draw a line from one circle to the next in ascending order; however, he must alternate the circles with numbers in them (1-13) with circles with letters in them (A-L). In other words, he is to connect the circles in order like this: 1-A-2-B-3-C-4-D-5-E and so on. Scoring is based on time taken to complete the test with lower scores being better.
Measured: Change from baseline to week 8 - 16 - 24
Changes in semantic fluency task
In the semantic fluency task, participants are asked to generate as many words as possible from a given category (animals) within a limited time (60 seconds); lower scores indicate greater impairment in verbal fluency.
Measured: Change from baseline to week 8 - 16 - 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2022
- Study start10 Dec 2022
- Primary completion15 Oct 2024
- Study completion15 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- 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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Barbara Borroni, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Investigators
- Barbara Borroni, MD, Principal investigator, Azienda Ospedaliera Spedali Civili, BresciaAlberto Benussi, MD, Principal investigator, University or Brescia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05643326
- Sponsor's protocol ID
- NP5395
- Acronym
- tACS@Home
- Status last verified
- Apr 2025
- First submitted
- 24 Nov 2022
- Last updated
- 17 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fries P. Neuronal gamma-band synchronization as a fundamental process in cortical computation. Annu Rev Neurosci. 2009;32:209-24. doi: 10.1146/annurev.neuro.051508.135603.
PubMed 19400723Iaccarino 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 27929004Adaikkan 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 31076275Martorell 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 30879788Herrmann CS, Rach S, Neuling T, Struber D. Transcranial alternating current stimulation: a review of the underlying mechanisms and modulation of cognitive processes. Front Hum Neurosci. 2013 Jun 14;7:279. doi: 10.3389/fnhum.2013.00279. eCollection 2013.
PubMed 23785325Benussi A, Cantoni V, Cotelli MS, Cotelli M, Brattini C, Datta A, Thomas C, Santarnecchi E, Pascual-Leone A, Borroni B. Exposure to gamma tACS in Alzheimer's disease: A randomized, double-blind, sham-controlled, crossover, pilot study. Brain Stimul. 2021 May-Jun;14(3):531-540. doi: 10.1016/j.brs.2021.03.007. Epub 2021 Mar 21.
PubMed 33762220Benussi A, Cantoni V, Grassi M, Brechet L, Michel CM, Datta A, Thomas C, Gazzina S, Cotelli MS, Bianchi M, Premi E, Gadola Y, Cotelli M, Pengo M, Perrone F, Scolaro M, Archetti S, Solje E, Padovani A, Pascual-Leone A, Borroni B. Increasing Brain Gamma Activity Improves Episodic Memory and Restores Cholinergic Dysfunction in Alzheimer's Disease. Ann Neurol. 2022 Aug;92(2):322-334. doi: 10.1002/ana.26411. Epub 2022 Jun 6.
PubMed 35607946Cantoni V, Casula EP, Tarantino B, Cupidi C, Huber N, Altomare D, Premi E, Zummo E, Esposito R, Leonardi C, Herukka SK, Solje E, Ferrari A, Cotelli MS, Gasparotti R, Martorana A, Fracassi C, Santarnecchi E, Koch G, Haapasalo A, Grassi M, Benussi A, Borroni B. Home-Based Gamma Transcranial Alternating Current Stimulation in Patients With Alzheimer Disease: A Randomized Clinical Trial. JAMA Netw Open. 2025 Dec 1;8(12):e2546556. doi: 10.1001/jamanetworkopen.2025.46556.
PubMed 41359335
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Markers of Clinical and Biological Response to Home Delivered Transcranial Alternating Current Stimulation (tACS) in Patients With Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT05643326
- Acronym / sponsor ID
- tACS@Home / NP5395
- Conditions
- Alzheimer Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di BresciaUniversity, hospital or other
- Study start
- 10 Dec 2022 (actual)
- Primary completion
- 15 Oct 2024 (actual)
- Study completion
- 15 Oct 2024 (actual)
- First posted
- 8 Dec 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.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Real tACS - Real tACS | Experimental | Device: 40 Hz transcranial alternating current stimulation42 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). |
| Sham tACS - Real tACS | Sham comparator | Device: 40 Hz transcranial alternating current stimulation, Device: Sham stimulation42 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Mild Alzheimer's disease (CDR 0.5 - 1)
- Age > 18 years
- Compliance in participation in training on the use of the therapeutic device
- Mini-Mental State Examination >26/30
Key exclusion criteria (11 listed)
- Cerebrovascular disorders
- Previous stroke
- Hydrocephalus
- Intra-cranial mass documented by MRI
- History of traumatic brain injury or other neurological diseases
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 |
|---|---|---|
| 40 Hz transcranial alternating current stimulation42 sessions of 40 Hz transcranial alternating current stimulation (5 days/week for 9 weeks) | Device | Real tACS - Real tACS, Sham tACS - Real tACS |
| Sham stimulation42 sessions of sham stimulation (5 days/week for 9 weeks) | Device | Sham tACS - Real tACS |
Primary outcome
Safety of transcranial alternating current stimulation delivered at home
Time frame: Through study completion, at week 24
Incidence of Treatment-Emergent Adverse Events as assessed by the incidence of adverse events graded from 1 (mild) to 5 (fatal).
Tolerability of transcranial alternating current stimulation delivered at home
Time frame: Through study completion, at week 24
Tolerability will be evaluated with percentage of compliance (number of delivered stimulations divided by number of programmed stimulations times one-hundred). The primary outcome will be reached if compliance will be >90%.
Changes in Clinical Dementia Rating scale (CDR) sum of boxes
Time frame: Difference between treatments (real and sham) at week 8
CDR-SB scores range from 0 to 18, with higher scores indicating worse cognition and daily function.
Changes in Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog)13
Time frame: Difference between treatments (real and sham) at week 8
ADAS-Cog13 scores range from 0 to 85, with higher scores indicating a greater deficit.
Changes in Face-Name Associative Memory Test (FNAT) scores
Time frame: Difference between treatments (real and sham) at week 8
The Face-Name Associative Memory Test is a cross-modal associative memory test, it includes 20 face-name pairs. The administration procedure starts with the presentation of 20 faces with each name and participants should read the name underneath the faces and try to learn each face-name pair. After 5 minutes, the faces are shown one by one and participants are asked to recall the associated names from 4 different names. The correct number of pairs recalled is recorded. The score ranges from 0 (worse performance) to 20 (best performance).
Changes in Alzheimer's Disease Assessment Scale Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
Time frame: Difference between treatments (real and sham) at week 8
ADCS-ADL scores range from 0 to 78, with lower scores indicating greater functional impairment.
17 secondary outcomes
Changes in Clinical Dementia Rating scale (CDR) sum of boxes
Time frame: Change from baseline to week 8 - 16 - 24
Changes in Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog)13
Time frame: Change from baseline to week 8 - 16 - 24
Changes in Rey Auditory Verbal Learning Test scores
Time frame: Change from baseline to week 8 - 16 - 24
Changes in Face-Name Associative Memory Test (FNAT) scores
Time frame: Change from baseline to week 8 - 16 - 24
Changes in the Neuropsychiatric Inventory (NPI-Q)
Time frame: Change from baseline to week 8 - 16 - 24
Changes in Caregiver Burden Inventory (CBI)
Time frame: Change from baseline to week 8 - 16 - 24
Changes in Alzheimer's Disease Assessment Scale Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
Time frame: Change from baseline to week 8 - 16 - 24
Change in SAI measurements
Time frame: Change from baseline to week 8 - 16 - 24
Change in EEG gamma power
Time frame: Change from baseline to week 8 - 16 - 24
Change in plasma NfL levels
Time frame: Change from baseline to week 8 - 16 - 24
Change in plasma GFAP levels
Time frame: Change from baseline to week 8 - 16 - 24
Change in plasma amyloid beta1-40 levels
Time frame: Change from baseline to week 8 - 16 - 24
Change in plasma amyloid beta1-42 levels
Time frame: Change from baseline to week 8 - 16 - 24
Change in plasma pTau217
Time frame: Change from baseline to week 8 - 16 - 24
Change in resting state MRI connectivity
Time frame: Change from baseline to week 8
Change in plasma TMT part B scores
Time frame: Change from baseline to week 8 - 16 - 24
Changes in semantic fluency task
Time frame: Change from baseline to week 8 - 16 - 24
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 17 Apr 2025.
- Background: PubMed 19400723Fries P. Neuronal gamma-band synchronization as a fundamental process in cortical computation. Annu Rev Neurosci. 2009;32:209-24. doi: 10.1146/annurev.neuro.051508.135603.
- Background: PubMed 27929004Iaccarino 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.
- Background: PubMed 31076275Adaikkan 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.
- Background: PubMed 30879788Martorell 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.
- Background: PubMed 23785325Herrmann CS, Rach S, Neuling T, Struber D. Transcranial alternating current stimulation: a review of the underlying mechanisms and modulation of cognitive processes. Front Hum Neurosci. 2013 Jun 14;7:279. doi: 10.3389/fnhum.2013.00279. eCollection 2013.
- Background: PubMed 33762220Benussi A, Cantoni V, Cotelli MS, Cotelli M, Brattini C, Datta A, Thomas C, Santarnecchi E, Pascual-Leone A, Borroni B. Exposure to gamma tACS in Alzheimer's disease: A randomized, double-blind, sham-controlled, crossover, pilot study. Brain Stimul. 2021 May-Jun;14(3):531-540. doi: 10.1016/j.brs.2021.03.007. Epub 2021 Mar 21.
- Background: PubMed 35607946Benussi A, Cantoni V, Grassi M, Brechet L, Michel CM, Datta A, Thomas C, Gazzina S, Cotelli MS, Bianchi M, Premi E, Gadola Y, Cotelli M, Pengo M, Perrone F, Scolaro M, Archetti S, Solje E, Padovani A, Pascual-Leone A, Borroni B. Increasing Brain Gamma Activity Improves Episodic Memory and Restores Cholinergic Dysfunction in Alzheimer's Disease. Ann Neurol. 2022 Aug;92(2):322-334. doi: 10.1002/ana.26411. Epub 2022 Jun 6.
- Derived from this study: PubMed 41359335Cantoni V, Casula EP, Tarantino B, Cupidi C, Huber N, Altomare D, Premi E, Zummo E, Esposito R, Leonardi C, Herukka SK, Solje E, Ferrari A, Cotelli MS, Gasparotti R, Martorana A, Fracassi C, Santarnecchi E, Koch G, Haapasalo A, Grassi M, Benussi A, Borroni B. Home-Based Gamma Transcranial Alternating Current Stimulation in Patients With Alzheimer Disease: A Randomized Clinical Trial. JAMA Netw Open. 2025 Dec 1;8(12):e2546556. doi: 10.1001/jamanetworkopen.2025.46556.
- Individual participant dataSharing planned: No
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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.
Barbara Borroni, MD principal investigator
Azienda Ospedaliera Spedali Civili, Brescia
Alberto Benussi, MD principal investigator
University or Brescia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 40 Hz transcranial alternating current stimulation in people with Alzheimer Disease, run by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia at 1 site in Italy.
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 4 inclusion and 11 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 17 Apr 2025. 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 Italy. 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?
Safety of transcranial alternating current stimulation delivered at home (time frame: Through study completion, at week 24). The study lists 6 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 NCT05643326, which also lists 8 linked publications.
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 17 Apr 2025.