Transcranial Alternating Current Stimulation in Lewy Body Dementia

Официальное название

Interventional Study to Evaluate the Effectiveness of Transcranial Alternating Current Stimulation (tACS) on Cognitive Performance in Patients With Lewy Body Dementia

Обзор

The aim of the study is to evaluate the safety, feasibility, clinical and biological efficacy, and predictors of efficacy of an intervention consisting of transcranial alternating current stimulation (tACS) in patients with Lewy Body Dementia (DLB). In neurodegenerative diseases, like DLB, the process of neurodegeneration is accompanied by a significant alteration in oscillatory activity. tACS is a neurophysiological method of non-invasive modulation of the excitability of the central nervous system that uses a mild electrical current. Recent studies have demonstrated the safety and efficacy of this method in modulating the natural brain oscillation frequencies underlying multiple cognitive processes, such as verbal memory, perception, and working memory. Preliminary data show that single stimulation with occipital α-tACS results in a significant improvement in visuospatial abilities and executive functions in patients wih DLB. The study is double blind, randomised and placebo-controlled, participants will be randomised into two groups: group 1, participants will receive real tACS for 2 weeks, from Wednesday to Tuesday (5 sessions/week, lasting approximately 60 minutes each); and group 2, participants will receive placebo tACS for 2 weeks (5 sessions/week, lasting approximately 60 minutes each). Visits will take place at the beginning of the study (T00), after 2 weeks (T02), and 12 weeks (T12, follow-up). During each visit, participants undergo the following procedures: (i) blood sampling, (ii) clinical and neuropsychological assessment, (iii) EEG, and (iv) TMS-EEG. The occurrence of adverse events will be monitored throughout the duration of the study. Specific biomarker analyses will be performed on the blood samples to study the pathophysiological mechanisms of the disease and the effect of the experimental intervention.

Вмешательства

• Устройство Transcranial Alternating Current Stimulation
  10 sessions (5 days/week for 2 weeks), each consisting in the application of a tACS session (real at 3 mA) at the cortical level for a duration of 60 minutes each.
• Устройство Sham Transcranial Alternating Current Stimulation
  10 sessions (5 days/week for 2 weeks), each consisting in the application of a sham tACS session at the cortical level 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 patient to distinguish between sham and real stimulation

Первичные конечные точки

• Incidence of Treatment-Emergent Adverse Events of Transcranial Alternating Current Stimulation Protocol [Срок оценки: Through study completion, at week 12]
• Feasibility of Transcranial Alternating Current Stimulation Protocol [Срок оценки: Through study completion, at week 12]
• Mini-Mental State Examination (MMSE) [Срок оценки: Change from baseline to week 12]
• Neuropsychiatric Inventory (NPI) [Срок оценки: Change from baseline to week 2 and 12]
• Qualitive Pentagon Test [Срок оценки: Change from baseline to week 2 and 12]
• Rey Auditory Verbal Learning Test (RAVLT) [Срок оценки: Change from baseline to week 2 and 12]
• Trail Making Test (TMT - AB) [Срок оценки: Change from baseline to week 2 and 12]
• Clock Drawing Test (CDT) [Срок оценки: Change from baseline to week 2 and 12]
• Rey-Osterrieth Complex Figure Test (ROCF) [Срок оценки: Change from baseline to week 2 and 12]
• Phonemic Fluency Test [Срок оценки: Change from baseline to week 2 and 12]

Вторичные конечные точки (7)

• Change in Biological Markers [Срок оценки: Change from baseline to week 2 and 12]
• Change in electroencephalography (EEG) [Срок оценки: Change from baseline to week 2 and 12]
• Change in TMS-EEG [Срок оценки: Change from baseline to week 2 and 12]
• Basic Activities of Daily Living (BADL) [Срок оценки: Baseline]
• Instrumental Activities of Daily Living (IADL) [Срок оценки: Baseline]
• Unified Parkinson's Disease Rating Scale - Part III (UPDRS-III) [Срок оценки: Baseline]
• Demographic characteristics [Срок оценки: Baseline]

Критерии участия

Критерии включения

• Male or female subjects aged over 18 at the time of signing the informed consent form;
• Presence of a clinical diagnosis of Lewy body dementia according to clinical criteria (McKeith et al., 2017)

Критерии исключения

• Age younger than that stated in the inclusion criteria;
• Incapacity to understand;
• Contraindications for tACS and TMS: patients with cardiac pacemakers and metal implants that are not compatible with electric or magnetic fields, history of epilepsy, current pregnancy (Safety questionnaire)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Италия · 1 центр

• IRCCS Istituto Centro San Giovanni Di Dio - Fatebenefratelli Brescia — Brescia

Публикации

• Aoki Y, Kazui H, Pascal-Marqui RD, Ishii R, Yoshiyama K, Kanemoto H, Suzuki Y, Sato S, Hata M, Canuet L, Iwase M, Ikeda M. EEG Resting-State Networks in Dementia with Lewy Bodies Associated with Clinical Symptoms. Neuropsychobiology. 2019;77(4):206-218. doi: 10.1159/000495620. Epub 2019 Jan 17. PMID 30654367
• Antal A, Alekseichuk I, Bikson M, Brockmoller J, Brunoni AR, Chen R, Cohen LG, Dowthwaite G, Ellrich J, Floel A, Fregni F, George MS, Hamilton R, Haueisen J, Herrmann CS, Hummel FC, Lefaucheur JP, Liebetanz D, Loo CK, McCaig CD, Miniussi C, Miranda PC, Moliadze V, Nitsche MA, Nowak R, Padberg F, Pascual-Leone A, Poppendieck W, Priori A, Rossi S, Rossini PM, Rothwell J, Rueger MA, Ruffini G, Schell PMID 28709880
• Amodio P, Wenin H, Del Piccolo F, Mapelli D, Montagnese S, Pellegrini A, Musto C, Gatta A, Umilta C. Variability of trail making test, symbol digit test and line trait test in normal people. A normative study taking into account age-dependent decline and sociobiological variables. Aging Clin Exp Res. 2002 Apr;14(2):117-31. doi: 10.1007/BF03324425. PMID 12092785
• Bagattini C, Mutanen TP, Fracassi C, Manenti R, Cotelli M, Ilmoniemi RJ, Miniussi C, Bortoletto M. Predicting Alzheimer's disease severity by means of TMS-EEG coregistration. Neurobiol Aging. 2019 Aug;80:38-45. doi: 10.1016/j.neurobiolaging.2019.04.008. Epub 2019 Apr 13. PMID 31077959
• Benussi A, Cantoni V, Rivolta J, Zoppi N, Cotelli MS, Bianchi M, Cotelli M, Borroni B. Alpha tACS Improves Cognition and Modulates Neurotransmission in Dementia with Lewy Bodies. Mov Disord. 2024 Nov;39(11):1993-2003. doi: 10.1002/mds.29969. Epub 2024 Aug 13. PMID 39136447
• Bonato C, Miniussi C, Rossini PM. Transcranial magnetic stimulation and cortical evoked potentials: a TMS/EEG co-registration study. Clin Neurophysiol. 2006 Aug;117(8):1699-707. doi: 10.1016/j.clinph.2006.05.006. Epub 2006 Jun 22. PMID 16797232
• Bortoletto M, Veniero D, Thut G, Miniussi C. The contribution of TMS-EEG coregistration in the exploration of the human cortical connectome. Neurosci Biobehav Rev. 2015 Feb;49:114-24. doi: 10.1016/j.neubiorev.2014.12.014. Epub 2014 Dec 22. PMID 25541459
• Hoy KE, Bailey N, Arnold S, Windsor K, John J, Daskalakis ZJ, Fitzgerald PB. The effect of gamma-tACS on working memory performance in healthy controls. Brain Cogn. 2015 Dec;101:51-6. doi: 10.1016/j.bandc.2015.11.002. Epub 2015 Nov 12. PMID 26580743

Идентификаторы

NCT: NCT07375771 · TACSDLB2

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗