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Transcranial Alternating Current Stimulation (tACS) Combined With Cognitive Training in Alzheimer's Disease (AD_tACSrehab)

21 settembre 2026 aggiornato da: Prof. Barbara Borroni, IRCCS Centro San Giovanni di Dio Fatebenefratelli

Interventional Study to Evaluate the Effectiveness of Transcranial Alternating Current Stimulation (tACS) Combined With Cognitive Training on Cognitive Performance in Patients With Alzheimer's Disease

The aim of the study is to evaluate the clinical and biological efficacy, as well as predictors of efficacy, of a home-based intervention combining transcranial alternating current stimulation (tACS) with individualized computerized cognitive training in patients with mild Alzheimer's disease (AD).

In neurodegenerative diseases, including AD, neurodegeneration is accompanied by alterations in brain oscillatory activity. Restoration of these oscillations through neuronal entrainment has shown beneficial effects in animal models, while previous studies in patients with AD have demonstrated that gamma-frequency tACS applied over the precuneus is safe and well tolerated and is associated with improvements in cognitive performance and cholinergic function, as well as modulation of brain oscillatory activity. Cognitive rehabilitation may also improve memory performance in patients with mild AD. Based on this evidence, the present study investigates a multimodal approach combining gamma-tACS with individualized computerized memory training.

The study is a multicenter, randomized, placebo-controlled, double-blind trial involving 30 participants with mild AD. Participants will be randomly assigned to one of two groups: Group 1 will receive real gamma-tACS for 8 weeks (5 sessions/week, 60 minutes/session) combined with cognitive training (2 sessions/week, 30 minutes/session); Group 2 will receive sham tACS according to the same schedule, combined with the same cognitive training. tACS will be applied over the precuneus. Treatment will initially be performed in the hospital and will subsequently be administered at home under remote supervision by the study team.

Assessments will be performed at baseline (T00), after 8 weeks of treatment (T08), and at follow-up visits at 16 weeks (T16) and 24 weeks (T24) from baseline. At each time point, participants will undergo clinical and neuropsychological assessment, blood sampling, and transcranial magnetic stimulation (TMS). The occurrence of adverse events will be monitored throughout the duration of the study.

The main objectives of the study are: 1) to evaluate the short- and long-term effects of the combined intervention on cognitive performance; 2) to investigate intervention-induced changes in biological markers of neurodegeneration, inflammation, and synaptic function; 3) to evaluate the effects of the intervention on cholinergic transmission through the TMS short-latency afferent inhibition (SAI) measure; and 4) to investigate potential predictors of treatment efficacy.

Panoramica dello studio

Tipo di studio

Interventistico

Iscrizione (Stimato)

30

Fase

  • Non applicabile

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

      • Milan, Italia
        • Non ancora reclutamento
        • IRCCS S. Maria Nascente - Fondazione Don Carlo Gnocchi
        • Contatto:
          • Francesca Baglio, MD
          • Numero di telefono: +390240308951
    • Brescia
      • Brescia, Brescia, Italia, 25125
        • Reclutamento
        • IRCCS Istituto Centro San Giovanni Di Dio - Fatebenefratelli
        • Investigatore principale:
          • Barbara Borroni, MD
        • Contatto:

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

Patients:

  • Male or female participants aged ≥18 years at the time of signing the informed consent form;
  • Clinical diagnosis of mild Alzheimer's disease (AD) according to current clinical criteria;
  • Availability of a caregiver who can assist the participant and who has successfully completed the required training for the use of the device at home.

Caregivers:

  • Male or female caregivers aged ≥18 years;
  • Compliance with participation in the in-hospital training;
  • Mini-Mental State Examination (MMSE) score >27/30.

Exclusion Criteria:

  • Age below that specified in the inclusion criteria;
  • Inability to understand;
  • Contraindications to tACS and TMS (e.g., presence of a cardiac pacemaker or metallic implants incompatible with electrical or magnetic fields, history of epilepsy, or current pregnancy, as assessed using the safety questionnaire).

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Triplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore fittizio: Finto tACS

Participants will receive individualized computerized memory training for 8 weeks (2 sessions/week, 30 minutes/session) through synchronous telerehabilitation. The memory training will be individualized based on each participant's performance on the Face-Name Association Task (FNAT) and will use an errorless learning approach.

40 at-home sessions (5 days/week for 8 weeks), each consisting of the application of sham tACS applied over the precuneus for a duration of 60 minutes each. The electrode placement will be identical to that used for real stimulation. However, the electrical current will be automatically interrupted approximately 5 seconds after the start of stimulation, making it impossible for the participant to distinguish between sham and real stimulation.

Sperimentale: Real tACS

40 at-home sessions (5 days/week for 8 weeks), each consisting of the application of tACS (real, 40 Hz) applied over the precuneus for a duration of 60 minutes each.

Participants will receive individualized computerized memory training for 8 weeks (2 sessions/week, 30 minutes/session) through synchronous telerehabilitation. The memory training will be individualized based on each participant's performance on the Face-Name Association Task (FNAT) and will use an errorless learning approach.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Mini-Mental State Examination (MMSE)
Lasso di tempo: Change from baseline to week 24

The global cognitive functioning will be assessed by Mini-Mental State Examination (MMSE); MMSE scores range from 0 to 30, with higher scores indicating a more preserved cognition.

Change from baseline to week 24
Semantic Fluency Test
Lasso di tempo: Change from baseline to week 8, 16, and 24

Lexical-semantic access and executive functioning will be evaluated by Semantic Fluency Test. Participant is asked to generate as many words as possible from a given category within a limited time (60 seconds); higher scores indicate better performance.

Change from baseline to week 8, 16, and 24
Trail Making Test (TMT - A, B)
Lasso di tempo: Change from baseline to week 8, 16, and 24

Executive function will be assessed using the Trail Making Test, including Part A (visual attention and processing speed) and Part B (task switching and cognitive flexibility). Higher completion times reflect poorer performance.

Change from baseline to week 8, 16, and 24
Rey Auditory Verbal Learning Test (RAVLT)
Lasso di tempo: Change from baseline to week 8, 16 and 24

Verbal memory will be assessed using the Rey Auditory Verbal Learning Test (RAVLT), including immediate recall (sum of trials), delayed recall after 15 minutes. Scores reflect the number of correctly recalled items.

Change from baseline to week 8, 16 and 24
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog-13)
Lasso di tempo: Change from baseline to week 8, 16 and 24

The ADAS-Cog-13 consists of 13 tasks assessing cognitive domains including memory, language, praxis, orientation, and attention. Total scores range from 0 to 85, with higher scores indicating greater cognitive impairment.

Change from baseline to week 8, 16 and 24
Face-Name Associative Memory Test (FNAT)
Lasso di tempo: Change from baseline to week 8, 16 and 24

The Face-Name Associative Memory Test is used to assess the participant's associative memory and is composed of encoding and retrieval phases, with higher scores indicating better function.

Change from baseline to week 8, 16 and 24
Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
Lasso di tempo: Change from baseline to week 8, 16 and 24

ADCS-ADL evaluates activities of daily living. The scores range from 0-78 with lower scores indicating more severe functional impairment.

Change from baseline to week 8, 16 and 24
Neuropsychiatric Inventory (NPI)
Lasso di tempo: Change from baseline to week 8, 16 and 24

Neuropsychiatric Inventory (NPI) is designed to be a structured clinical interview about neuropsychiatric and behavioral symptoms; the score ranges from 0 (no symptoms) to 144 (severe symptoms).

Change from baseline to week 8, 16 and 24
Clinical Dementia Rating scale - Sum of Boxes (CDR-SoB)
Lasso di tempo: Change from baseline to week 8, 16 and 24

The Clinical Dementia Rating-Sum of Boxes (CDR-SB) assesses cognitive and functional impairment across six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Total scores range from 0 to 18, with higher scores indicating greater cognitive and functional impairment.

Change from baseline to week 8, 16 and 24
Clinical Dementia Rating scale - Global Score (CDR-GS)
Lasso di tempo: Change from baseline to week 8, 16 and 24

The Clinical Dementia Rating Global Score (CDR-GS) assesses the overall severity of cognitive and functional impairment across six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Global scores range from 0 to 3, with higher scores indicating greater impairment.

Change from baseline to week 8, 16 and 24
Zarit Burden Interview (ZBI)
Lasso di tempo: Change from baseline to week 8, 16, and 24

The Zarit Burden Interview (ZBI) assesses the perceived burden experienced by caregivers of individuals with dementia. It consists of 22 items rated on a 5-point scale. Total scores range from 0 to 88, with higher scores indicating greater caregiver burden.

Change from baseline to week 8, 16, and 24

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Change in SAI measurements
Lasso di tempo: Change from baseline to week 8, 16, and 24

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 percent of the unconditioned motor evoked potential.

Change from baseline to week 8, 16, and 24
Change From Baseline in Biological Marker Concentrations
Lasso di tempo: Change from baseline to week 8, 16, and 24

A venous blood draw will be performed at each timepoint. Samples will be processed for serum, plasma, and DNA extraction. Changes from baseline in biological marker concentrations, including plasma p-tau217, will be evaluated over time.

Change from baseline to week 8, 16, and 24
Demographic characteristics
Lasso di tempo: Baseline

Demographic characteristics (age, gender, and level of education) will be evaluated as predictors of treatment efficacy and examined for associations with differential treatment response.

Baseline
Baseline Clinical Dementia Rating-Sum of Boxes (CDR-SB)
Lasso di tempo: Baseline

The Clinical Dementia Rating-Sum of Boxes (CDR-SB) will be used to assess disease severity at baseline and evaluated as a predictor of treatment efficacy and examined for associations with differential treatment response. The CDR-SB assesses cognitive and functional impairment across six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Total scores range from 0 to 18, with higher scores indicating greater disease severity.

Baseline
Baseline Clinical Dementia Rating - Global Score (CDR-GS)
Lasso di tempo: Baseline

The Clinical Dementia Rating - Global Score (CDR-GS) will be used to assess disease severity at baseline and evaluated as a predictor of treatment efficacy and examined for associations with differential treatment response. The CDR-SB assesses cognitive and functional impairment across six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Global scores range from 0 to 3, with higher scores indicating greater impairment.

Baseline
Level of Education and Occupational Attainment as Proxies of Cognitive Reserve
Lasso di tempo: Baseline

Level of education and occupational attainment will be assessed at baseline as proxy measures of cognitive reserve and examined for associations with differential treatment response.

Baseline
Plasma Biomarker Profile
Lasso di tempo: Baseline

The plasma biomarker profile will be evaluated as a predictor of treatment efficacy and examined for associations with differential treatment response.

Baseline

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

16 settembre 2026

Completamento primario (Stimato)

1 settembre 2031

Completamento dello studio (Stimato)

1 settembre 2032

Date di iscrizione allo studio

Primo inviato

14 settembre 2026

Primo inviato che soddisfa i criteri di controllo qualità

21 settembre 2026

Primo Inserito (Effettivo)

24 settembre 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

24 settembre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

21 settembre 2026

Ultimo verificato

1 settembre 2026

Maggiori informazioni

Termini relativi a questo studio

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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