Personalized non-invasive magnetic and electrical stimulation of memory networks in mild Alzheimer's

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

This study will try a personalized combination of magnetic (iTBS) and electrical (tACS) non-invasive brain stimulation to improve memory and brain connectivity in people with mild Alzheimer's disease.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 50 Years to 85 Years
• Sex: All
• Sponsor: I.R.C.C.S. Fondazione Santa Lucia (Academic / other)
• Locations: 2 sites (Rome, Italy and 1 other locations)
• Trial ID: NCT07075770 on ClinicalTrials.gov

What this trial studies

People with mild, biomarker-confirmed Alzheimer's will be randomized to receive personalized intermittent theta-burst rTMS (iTBS) plus tACS, iTBS with sham tACS, or double sham. Stimulation targets Default Mode Network regions such as the precuneus and is delivered noninvasively using individualized protocols. Outcomes include cognitive and behavioral testing, plasma biomarkers (baseline, week 12, week 24), MRI, TMS-EEG, and immersive virtual environment assessments, with visits at baseline, week 12, and week 24. Safety monitoring and adverse event recording are performed throughout the approximately six-month participation period.

Who should consider this trial

Good fit: Ideal candidates are people with mild Alzheimer's (MMSE 20–28, CDR ≤1) who have biomarker evidence of amyloid pathology, a stable medication regimen, and a caregiver available to support study visits.

Not a fit: Patients with more advanced dementia, negative amyloid biomarkers, unstable medical conditions, prohibited medications, or who cannot attend in-person visits are unlikely to benefit from or be eligible for this intervention.

Why it matters

Potential benefit: If successful, this approach could improve memory and restore network connectivity, potentially slowing cognitive decline in mild Alzheimer's disease.

How similar studies have performed: Previous rTMS and tACS studies have shown mixed but sometimes modest cognitive or neuroplasticity effects, while combining personalized DMN-targeted iTBS and tACS is a novel and relatively untested approach.

Eligibility criteria

Inclusion Criteria:

* Patients with a diagnosis of AD according to IWG criteria
* 20 \> MMSE \< 28
* Patients with CSF specific biomarker profile or with a positive Amyloid Pet Scan consistent with the presence of amyloid pathology
* Global Clinical Dementia Rating (CDR) ≤1
* Previous decline in cognition for more than six months as documented in patient medical records
* A caregiver available and living in the same household or interacting with the patient and available
* Patients living at home or nursing home setting without continuous nursing care
* General health status acceptable for a participation in a 6-month clinical trial
* Stable pharmacological treatment for at least one month prior to screening
* No regular intake of prohibited medications.
* Signed informed consent by the patient. If there are any doubts that the patient is mentally capable of giving informed consent, the patient will be examined and verified to be mentally capable by an independent physician/ neurologist, prior to the initiation of any study specific procedure. Signed consent of the caregiver

Exclusion Criteria:

* Failure to undergo screening or baseline exams
* Hospitalization or change in chronic concomitant medications one month before the screening or during the screening period
* Clinical, laboratory, or neuroimaging results consistent with:

  1. other primary degenerative dementia (Lewy body dementia, frontotemporal dementia, Huntington's disease, Creutzfeldt-Jakob disease, Down syndrome, etc.);
  2. other neurodegenerative conditions (Parkinson's disease, amyotrophic lateral sclerosis, etc.);
  3. orthostatic hypotension and autonomic disorders
  4. cerebrovascular disease (major infarction, a strategic infarction or multiple lacunar infarctions, extensive white matter lesions \> one quarter of total white matter);
  5. other central nervous system diseases (severe traumatic brain injury, tumors, subdural hematoma, or other space-occupying processes, etc.);
  6. seizure disorder.
  7. Other infectious, metabolic, or systemic diseases affecting the central nervous system (syphilis, existing hypothyroidism, current vitamin B12 or folate deficiency, serum electrolytes outside normal limits, juvenile diabetes, etc.).
* A current DSM-V diagnosis of major depression, schizophrenia, or bipolar disorder.
* Clinically significant, advanced, or unstable disease that may interfere with primary or secondary variable assessments and may affect the assessment of the patient's clinical or mental state, or expose the patient to special risk, such as:

  1. Disability that may prevent the patient from completing all study requirements (e.g., blindness, deafness, severe language difficulties, etc.);
  2. Opioid-containing analgesics
  3. Suspected or known drug or alcohol abuse, i.e., more than about 60 g of alcohol (about 1 liter of beer or 500 ml of wine) per day, indicated by a high mean corpuscular volume (MCV) above the normal value at screening;
  4. Any condition that, in the investigator's judgment, makes the patient unsuitable for inclusion

Where this trial is running

Rome, Italy and 1 other locations

• IRCCS Santa Lucia Foundation — Rome, Italy, Italy (Recruiting)
• I.R.C.C.S. Centro Neurolesi Bonino Pulejo — Messina, Sicily, Italy (Not_yet_recruiting)

Study contacts

• Principal investigator: Giacomo Koch, Prof. — IRCCS Santa Lucia Foundation
• Study coordinator: Giacomo Koch, Prof

Conditions Alzheimer Disease; Non Invasive Brain Stimulation; Transcranial Magnetic Stimulation; Intermittent Theta Burst Stimulation; Transcranial Electrical Stimulation; Transcranial Alternating Current Stimulation; Default Mode Network