Transcranial Alternating Current Stimulation in Frontotemporal Dementia

Официальное название

Cross-over Study to Evaluate the Safety, Tolerability, and Clinical Efficacy of Transcranial Alternating Current Stimulation (tACS) in Patients With Frontotemporal 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 Frontotemporal Dementia (FTD). In addition to typical symptoms, FTD also present alterations in brain oscillations. In animal models of neurodegeneration, restoration of oscillations via neuronal "entrainment" phenomena has demonstrated a significant reduction in toxic protein accumulation, resulting in improved cognitive function. tACS is a neurophysiological noninvasive method of neuromodulation increasingly studied for its therapeutic potential. It has been shown to safely modulate the oscillatory frequencies underlying multiple cognitive functions, including verbal memory, perception, and working memory. In light of this evidence, it is proposed to apply a single-session treatment of β-tACS stimulation in patients with FTD and to evaluate its clinical effects, oscillatory modifications by EEG, and changes in neurophysiological indices such as short intracortical inhibition (SICI) and intracortical facilitation (ICF), both compromised in the disease. The study has a cross-over design (multicenter, randomized, placebo-controlled and double-blind), with FTD patients randomly assigned to one of the two arms: i) Group 1, who will receive a real tACS session first (1h); ii) Group 2, who will instead undergo a sham tACS session (1h). In the next phase (cross-over), one week after the first phase, the groups will reverse the treatment: Group 1 will receive tACS sham and Group 2 will receive real tACS. The main objectives of the study are: \[1\] to evaluate the safety and tolerability of the single tACS treatment session; \[2\] to investigate the effects of the protocol on (short-term) cognitive performance in patients with FTD; \[3\] to verify intervention-induced changes in brain synchronization; \[4\] to evaluate changes in neurophysiological indices following treatment; and \[5\] evaluate any predictors of efficacy.

Вмешательства

• Устройство Transcranial Alternating Current Stimulation
  The session will consist of the application of a session of tACS (real at 2.5 mA) at the cortical level for a duration of 60 minutes.
• Устройство Sham Transcranial Alternating Current Stimulation
  Application of sham tACS session at the cortical level for a duration of 60 minutes. The electrode placement will be identical to that used for real stimulation. However, the electrical current will be automatically interrupted approximately 30 seconds after the start of stimulation, making it impossible for the patient to distinguish between sham and real stimulation.

Первичные конечные точки

• Safety and Feasibility of Transcranial Alternating Current Stimulation Protocol [Срок оценки: Periprocedurally, an average 1 week]
• Phonemic Fluency Test [Срок оценки: Immediately before and immediately after first stimulation. Immediately before and immediately after second stimulation, after a week.]
• Semantic Fluency Test [Срок оценки: Immediately before and immediately after first stimulation. Immediately before and immediately after second stimulation, after a week.]
• Trail Making Test (TMT - AB) [Срок оценки: Immediately before and immediately after first stimulation. Immediately before and immediately after second stimulation, after a week.]
• Digit Span Test [Срок оценки: Immediately before and immediately after first stimulation. Immediately before and immediately after second stimulation, after a week.]
• Modified Emotion Recognition Test [Срок оценки: Immediately after first stimulation. Immediately after second stimulation, after a week.]
• Berg's Card Sorting Task [Срок оценки: At the end of first stimulation. At the end of second stimulation, after a week.]
• Go/No-Go Task [Срок оценки: At the end of first stimulation. At the end of second stimulation, after a week.]

Вторичные конечные точки (3)

• Change in electroencephalography (EEG) [Срок оценки: Immediately before and immediately after first stimulation. Immediately before and immediately after second stimulation, after a week.]
• Effectiveness in restoring neurotransmission [Срок оценки: Immediately before and immediately after first stimulation. Immediately before and immediately after second stimulation, after a week.]
• Demographic characteristics [Срок оценки: Baseline]

Критерии участия

Критерии включения

• Male or female subjects aged over 40 years at the time of signing the informed consent form;
• Presence of a clinical diagnosis of Frontotemporal Dementia according to clinical criteria (Rascovsky et al., 2011; Gorno-Tempini et al., 2011).

Критерии исключения

• Age younger than that stated in the inclusion criterion;
• Inability to understand;
• Contraindications for tACS and TMS: cardiac pacemaker carriers 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

Перекрёстный дизайн

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Италия · 1 центр

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

Публикации

• Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC, Seelaar H, Dopper EG, Onyike CU, Hillis AE, Josephs KA, Boeve BF, Kertesz A, Seeley WW, Rankin KP, Johnson JK, Gorno-Tempini ML, Rosen H, Prioleau-Latham CE, Lee A, Kipps CM, Lillo P, Piguet O, Rohrer JD, Rossor MN, Warren JD, Fox NC, Galasko D, Salmon DP, Black SE, Mesulam M, Weintraub S, Dickerson BC, Diehl-Schmi PMID 21810890
• Pettorruso M, Miuli A, Di Natale C, Montemitro C, Zoratto F, De Risio L, d'Andrea G, Dannon PN, Martinotti G, di Giannantonio M. Non-invasive brain stimulation targets and approaches to modulate gambling-related decisions: A systematic review. Addict Behav. 2021 Jan;112:106657. doi: 10.1016/j.addbeh.2020.106657. Epub 2020 Sep 13. PMID 32987305
• Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, Paulus W, Hummel F, Boggio PS, Fregni F, Pascual-Leone A. Transcranial direct current stimulation: State of the art 2008. Brain Stimul. 2008 Jul;1(3):206-23. doi: 10.1016/j.brs.2008.06.004. Epub 2008 Jul 1. PMID 20633386
• Nishida K, Yoshimura M, Isotani T, Yoshida T, Kitaura Y, Saito A, Mii H, Kato M, Takekita Y, Suwa A, Morita S, Kinoshita T. Differences in quantitative EEG between frontotemporal dementia and Alzheimer's disease as revealed by LORETA. Clin Neurophysiol. 2011 Sep;122(9):1718-25. doi: 10.1016/j.clinph.2011.02.011. Epub 2011 Mar 10. PMID 21396882
• Monaco M, Costa A, Caltagirone C, Carlesimo GA. Forward and backward span for verbal and visuo-spatial data: standardization and normative data from an Italian adult population. Neurol Sci. 2013 May;34(5):749-54. doi: 10.1007/s10072-012-1130-x. Epub 2012 Jun 12. PMID 22689311
• Lindau M, Jelic V, Johansson SE, Andersen C, Wahlund LO, Almkvist O. Quantitative EEG abnormalities and cognitive dysfunctions in frontotemporal dementia and Alzheimer's disease. Dement Geriatr Cogn Disord. 2003;15(2):106-14. doi: 10.1159/000067973. PMID 12566600
• Iyer MB, Mattu U, Grafman J, Lomarev M, Sato S, Wassermann EM. Safety and cognitive effect of frontal DC brain polarization in healthy individuals. Neurology. 2005 Mar 8;64(5):872-5. doi: 10.1212/01.WNL.0000152986.07469.E9. PMID 15753425
• Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, Ogar JM, Rohrer JD, Black S, Boeve BF, Manes F, Dronkers NF, Vandenberghe R, Rascovsky K, Patterson K, Miller BL, Knopman DS, Hodges JR, Mesulam MM, Grossman M. Classification of primary progressive aphasia and its variants. Neurology. 2011 Mar 15;76(11):1006-14. doi: 10.1212/WNL.0b013e31821103e6. Epub 2011 Feb 16. PMID 21325651

Идентификаторы

NCT: NCT07505784 · BetaTACSFTD

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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