RecruitingNot ApplicableNCT07075770

Novel Personalized Non Invasive Combined Magnetic and Electrical Stimulation of the DMN in Mild AD Patients

Novel Personalized Non Invasive Combined Magnetic and Electrical Stimulation of the Default Mode Network in Mild AD Patients (CMES-AD)


Sponsor

I.R.C.C.S. Fondazione Santa Lucia

Enrollment

60 participants

Start Date

Jan 1, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

Alzheimer's disease (AD) is increasingly recognized as a disorder marked by early synaptic dysfunction and disrupted brain network connectivity, beyond the traditional focus on amyloid pathology. Synaptic plasticity (crucial for learning and memory) is compromised in AD and represents a promising therapeutic target. In particular, alterations in the Default Mode Network (DMN), especially in regions like the precuneus, suggest that restoring connectivity and enhancing plasticity may improve cognitive outcomes. This project proposes a novel, precision-delivered non-invasive brain stimulation protocol that combines repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS) over the DMN. The intervention will be evaluated through cognitive testing, blood-based biomarkers, MRI and TMS-EEG, alongside immersive virtual environments to assess sensorimotor and cognitive function. This approach aims to test neuromodulation strategies capable of slowing neurodegeneration and supporting early detection and rehabilitation in AD.


Eligibility

Min Age: 50 YearsMax Age: 85 Years

Plain Language Summary

Simplified for easier understanding

This study is testing a new non-invasive brain stimulation technique — combining magnetic and electrical stimulation — to improve memory and thinking in people with mild Alzheimer's disease. **You may be eligible if...** - You have been diagnosed with Alzheimer's disease according to recognized criteria - Your cognitive testing (MMSE) score is between 20 and 28 (mild stage) - You have had a brain scan or spinal fluid test confirming amyloid buildup (a hallmark of Alzheimer's) - Your overall dementia rating (CDR) is 1 or less - You have a caregiver who lives with you or interacts with you regularly - You have been on stable Alzheimer's medications for at least one month before the study **You may NOT be eligible if...** - Your dementia is moderate to severe (CDR above 1) - You are on medications known to interfere with the study treatment - You are unable to give your own informed consent (as verified by an independent physician) Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DEVICECombined iTBS-tACS

The iTBS-tACS will be applied over the precuneus and last for 190 s, with the tACS electrode positioned on the scalp and the iTBS coil positioned just above it. The iTBS protocol will consist of 600 pulses, delivered in 20 trains of 10 bursts with an interval of 8 seconds between each train. Each burst consists of three pulses at 50Hz, repeated at 5Hz. The total duration will therefore be 190 seconds. iTBS and tACS will be synchronized using a BrainTrigger and SIGNAL Software so that both stimulations will start simultaneously

DEVICEiTBS-sham tACS

The iTBS-tACS will be applied over the precuneus and last for 190 s, with the tACS electrode positioned on the scalp and the iTBS coil positioned just above it. The iTBS protocol will consist of 600 pulses, delivered in 20 trains of 10 bursts with an interval of 8 seconds between each train. Each burst consists of three pulses at 50Hz, repeated at 5Hz. The total duration will therefore be 190 seconds. For the tACS sham condition, the electric current will not be applied, but there will be a 2 s 1 mA ramp up and 2 s 1 mA ramp down, to give the participant real stimulation feelings.

DEVICEsham iTBS- sham tACS

The iTBS-tACS will be applied over the precuneus and last for 190 s, with the tACS electrode positioned on the scalp and the iTBS coil positioned just above it. The iTBS protocol will consist of 600 pulses, delivered in 20 trains of 10 bursts with an interval of 8 seconds between each train. Each burst consists of three pulses at 50Hz, repeated at 5Hz. The total duration will therefore be 190 seconds. For the iTBS sham condition, stimulation was delivered with the coil angled at 90°, with only the edge of the coil resting on the scalp.. For the tACS sham condition, the electric current will not be applied, but there will be a 2 s 1 mA ramp up and 2 s 1 mA ramp down, to give the participant real stimulation feelings.


Locations(2)

IRCCS Santa Lucia Foundation

Rome, Italy, Italy

I.R.C.C.S. Centro Neurolesi Bonino Pulejo

Messina, Sicily, Italy

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NCT07075770


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