Transcranial Alternating Current Stimulation in Lewy Body Dementia

Official title

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

Overview

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.

Interventions

• Device 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.
• Device 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

Primary outcome measures

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

Secondary outcome measures (7)

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

Eligibility criteria

Inclusion criteria

• 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)

Exclusion criteria

• 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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Italy · 1 center

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

Publications

• 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

Identifiers

NCT: NCT07375771 · TACSDLB2

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗