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

NCT05643326 | Completed

• 1 other identifier: NP5395
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (6)

• 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).

  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%.

  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.

  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.

  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).

  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.

  Difference between treatments (real and sham) at week 8

Secondary Outcomes (17)

• Changes in Clinical Dementia Rating scale (CDR) sum of boxes

  Change from baseline to week 8 - 16 - 24

• Changes in Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog)13

  Change from baseline to week 8 - 16 - 24

• Changes in Rey Auditory Verbal Learning Test scores

  Change from baseline to week 8 - 16 - 24

• Changes in Face-Name Associative Memory Test (FNAT) scores

  Change from baseline to week 8 - 16 - 24

• Changes in the Neuropsychiatric Inventory (NPI-Q)

  Change from baseline to week 8 - 16 - 24

Study Arms (2)

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).

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).

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

Interventions

40 Hz transcranial alternating current stimulation DEVICE

42 sessions of 40 Hz transcranial alternating current stimulation (5 days/week for 9 weeks)

Real tACS - Real tACS; Sham tACS - Real tACS

Sham stimulation DEVICE

42 sessions of sham stimulation (5 days/week for 9 weeks)

Sham tACS - Real tACS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: lead

Study Sites (1)

ASST Spedali Civili di Brescia

Brescia, BS, 25123, Italy

Location

Related Publications (8)

• 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.

  PMID: 19400723 BACKGROUND

• 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.

  PMID: 27929004 BACKGROUND

• 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.

  PMID: 31076275 BACKGROUND

• 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.

  PMID: 30879788 BACKGROUND

• Herrmann 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.

  PMID: 23785325 BACKGROUND

• Benussi 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.

  PMID: 33762220 BACKGROUND

• Benussi 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.

  PMID: 35607946 BACKGROUND

• Cantoni 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.

  PMID: 41359335 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Barbara Borroni, MD

  Azienda Ospedaliera Spedali Civili, Brescia

  PRINCIPAL INVESTIGATOR

• Alberto Benussi, MD

  University or Brescia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: November 24, 2022
• First Posted: December 8, 2022
• Study Start: December 10, 2022
• Primary Completion: October 15, 2024
• Study Completion: October 15, 2024
• Last Updated: April 17, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)