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

21 de septiembre de 2026 actualizado por: 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.

Descripción general del estudio

Tipo de estudio

Intervencionista

Inscripción (Estimado)

30

Fase

  • No aplica

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

      • Milan, Italia
        • Aún no reclutando
        • IRCCS S. Maria Nascente - Fondazione Don Carlo Gnocchi
        • Contacto:
          • Francesca Baglio, MD
          • Número de teléfono: +390240308951
    • Brescia
      • Brescia, Brescia, Italia, 25125
        • Reclutamiento
        • IRCCS Istituto Centro San Giovanni Di Dio - Fatebenefratelli
        • Investigador principal:
          • Barbara Borroni, MD
        • Contacto:

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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).

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Triple

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador falso: TAC falso

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.

Experimental: 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.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Mini-Mental State Examination (MMSE)
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Change in SAI measurements
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: Baseline

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

Baseline

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Estimado)

16 de septiembre de 2026

Finalización primaria (Estimado)

1 de septiembre de 2031

Finalización del estudio (Estimado)

1 de septiembre de 2032

Fechas de registro del estudio

Enviado por primera vez

14 de septiembre de 2026

Primero enviado que cumplió con los criterios de control de calidad

21 de septiembre de 2026

Publicado por primera vez (Actual)

24 de septiembre de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

24 de septiembre de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

21 de septiembre de 2026

Última verificación

1 de septiembre de 2026

Más información

Términos relacionados con este estudio

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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