Evaluate the Safety and Feasibility of tACS With the Miamind Neurostimulator in Healthy Participants

Study Overview
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Brief Summary
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The present study aims to assess the safety and feasibility of repeated transcranial alternating current stimulation (tACS) by the Miamind Neurostimulator in a cohort of healthy participants. Based on the findings of this investigation, subsequent clinical trials assessing the efficiency of tACS by the Miamind Neurostimulator for treatment of Alzheimer's Disease will be conducted.

Detailed Description
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The pathological hallmarks of Alzheimer's Disease (AD) are extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles of hyperphosphorylated tau deposition in the brain together with neuroinflammation and microglial activation. These alterations lead to synaptic dysfunction, neuronal loss, and subsequently to brain circuit and brain oscillation disruption, resulting in cognitive decline. Recent studies have shown a positive effect of neural entrainment at gamma frequency (30-80 Hz). Transcranial alternating current stimulation (tACS) utilizes low amplitude alternating currents, allowing for frequency and region-specific brain oscillation entrainment showing positive results regarding improvement of cognitive functions in healthy participants and Alzheimer's Disease patients. Miamind Neurostimulator is a patient specific MRI-based 3D printed medical device that permits electrical stimulation and recording on up to 32 electrode channels and thus allows for simultaneous, multifocal, and targeted brain stimulation. tACS is non- invasive, well tolerated by users and considered safe with no persistent adverse events reported.

Official Title
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A Prospective, Single-Arm, Monocentric Pilot Study to Evaluate the Safety and Feasibility of Transcranial Alternate Current Stimulation With the Miamind Neurostimulator in Healthy Participants

Conditions
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Healthy Participants, Healthy Population

Intervention / Treatment
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* Device: Personalized Miamind Neurostimulator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who are overtly healthy as determined by medical evaluation including medical history and physical examination. Able and willing to provide voluntary written Informed Consent and sign the ICF to participate in the study prior to any study-related procedure. Must have the ability to comply with protocol-related tests, appointments, and procedures. Age over 18 years old. Knowledge of the German language (B1 or higher). No history of intellectual or learning disability; at least 8 grades of school. Non-disturbing hairstyle or headdress that enables electrode contact with the scalp judged by the investigator. Exclusion Criteria: Any acute or chronic disease/disorder (e.g., cerebral, psychiatric, cardiovascular, pulmonary, metabolic, skin etc.) History of traumatic brain injury or other diseases of the central nervous system. History of seizures, diagnosis of epilepsy, or abnormal (epileptiform) EEG, or immediate (1st-degree relative) family history of epilepsy. Diagnosis of substance abuse. Participant is under the influence of alcohol, and consumption of narcotics or benzodiazepines, or other sleeping medications prior to the procedure. All female participants that are not post-menopausal (defined as at least 12 months of spontaneous amenorrhea in women over 45 years old) or surgically sterile (e.g. bilateral tubal ligation, hysterectomy, bilateral oophorectomy) will be required to have a pregnancy test; any participant who is pregnant or breastfeeding will not be enrolled in the study. Metal implants (excluding dental fillings) or devices such as a pacemaker, cardioverter defibrillator, medication pump, nerve stimulator, Transcutaneous Electrical Nerve Stimulator (TENS) unit, ventriculoperitoneal shunt, and cochlear implant, unless cleared by the study MD. Contraindications for undergoing MRI. Ongoing participation in any other interventional clinical study with an investigational drug or another MD within the 30 days preceding and during the present investigation. Participants not suitable for the study based on a holistic consideration of the participant's history and the PI's medical expertise. No vulnerable subject is enrolled on this study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Interventional Model Description: The present study aims to assess the safety and feasibility of employing repeated (4 sessions at 4 days) transcranial alternating current stimulation (tACS) through the utilization of the Miamind Neurostimulator in a cohort of healthy participants.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 60 min session of 40Hz tACS by Miamind Neurostimulator<br>The clinical study will enroll eight (8) participants who will undergo four (4) tACS sessions (one per day) within 4 consecutive days. The tACS intervention will last 60 min in total. The stimulation frequency will be 40 Hz with max 1 mA/electrode and total of max 2 mA across all active electrodes (peak-to-baseline). | Device: Personalized Miamind Neurostimulator<br>* 60 min. 40 Hz max. 1mA / electrode & total of max. 2 mA across all electrodes. 30- s ramp-up personalised intervention based on individual modelling of electric field distribution to maximise therapeutic effect in the target region. Three target regions, consecutively stimulated (20min each).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence of Treatment-Emergent Adverse Events | Safety of the Treatment defined as the proportion of study participants free of serious adverse device effects and unanticipated serious adverse device effects (SADE and USADE) assessed via a safety questionnaire and medical evaluation. | up to 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and comfort: questionnaire | Adverse Events and comfort of tACS and the medical device are reported by questionnaires following stimulation of each target region at visit °3 & °4 and following sequential stimulation of multiple target regions at visit °5 & °6. | up to 2 weeks | 
| Evaluation of functional impact of tACS on Attention and Concentration: d2-R attention test | Changes in d2-R attention test are reported to document the functional impact of tACS on concentration and attention before and after stimulation of each target region at visit °3 & °4 and before and after sequential stimulation of multiple target regions at visit °5 & °6. The d2-R attention test measures processing speed, rule compliance, and quality of performance as estimation of attention and concentration and scores them as the following separate items: speed, concentration, carefulness. Each item is scored from 20-80. A higher score indicates better performance. | up to 2 weeks | 
| Evaluation of functional impact of tACS on oscillatory activity: Electroencephalography (EEG) | Quantification of EEG measurements to document the functional impact of tACS on oscillatory activity in individual frequency bands (delta, theta, alpha, beta, gamma) and EEG-biomarkers (alpha peak frequency, Vigilance) before and after stimulation of each target region at visit °3 & °4 & °5 & °6. | up to 2 weeks | 
| Cognitive Evaluation: Montreal Cognitive Assessment (MoCA) | MoCA scores are documented before and after visit °3 and after visit °6 to evaluate the impact of repeated tACS on cognitive performance. The MoCA has a total scoring range of 0-30, with the score based on the number of correct answers made in each of the 7 following items: Visuospatial/Executive, Naming, Memory/delayed recall, Attention, Language, Abstraction, Orientation. Sub-scores and total score are reported. A lower total score indicate greater cognitive impairment. | up to 2 weeks | 
| Participant coherence and satisfaction questionnaire | The subjective impression and satisfaction of the participant regarding the device and the intervention is documented using a one-time questionnaire at the end of the study. | up to 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer Disease, tACS, Memory Problems, Cognitive Impairment, Cognitive Performance, Safety and Tolerability, Feasibility