Non-invasive brain stimulation for Alzheimer's Disease

Gamma Induction for Amyloid Clearance in Alzheimer's Disease

Phase1; Phase2 Interventional Massachusetts General Hospital · NCT03880240

This study is testing whether daily sessions of non-invasive brain stimulation can help people with early to moderate Alzheimer's Disease and Mild Cognitive Impairment by reducing harmful proteins in the brain.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment55 (estimated)
Ages45 Years and up
SexAll
SponsorMassachusetts General Hospital Academic / other
Drugs / interventionsradiation
Locations1 site (Boston, Massachusetts)
Trial IDNCT03880240 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of multiple daily sessions of non-invasive brain stimulation on brain activity in individuals with early to moderate Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI). Participants will undergo a series of assessments including cognitive testing, PET imaging for amyloid and tau, and various brain stimulation techniques. The study is designed as a sham-controlled, double-blind trial, enrolling approximately 55 individuals who will be randomly assigned to receive either active or sham stimulation. The goal is to determine if this intervention can effectively reduce amyloid and tau levels in the brain, potentially altering the course of the disease.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 45 and older with a clinical diagnosis of early to moderate Alzheimer's Disease or Mild Cognitive Impairment and confirmed amyloid positivity.

Not a fit: Patients with poorly controlled migraines or other significant neurological disorders may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new non-pharmacological treatment option that may slow the progression of Alzheimer's Disease.

How similar studies have performed: Other studies using non-invasive brain stimulation techniques have shown promise, but this specific approach is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Clinical Diagnosis of early to moderate AD\*

  * Mini Mental State Examination (MMSE) ≥ 18
  * Clinical Dementia Rating (CDR) ≥ 0.5
  * Demonstration or history of memory impairments.

    * Confirmation of diagnosis will be made by the study MD based on a holistic consideration of the participant's cognitive evaluation and history.
* Amyloid positive PET imaging
* At least 45 years old
* On a stable dose of medications for memory loss including cholinesterase inhibitors (e.g. donepezil, rivastigmine or memantine) as defined as 6 consecutive weeks of treatment at an unchanging dose
* Minimum of completed 8th grade education
* No history of intellectual disability

Exclusion Criteria:

* Current history of poorly controlled migraines including chronic medication for migraine prevention
* Current or past history of any neurological disorder other than dementia, such as epilepsy, stroke (cortical stroke), progressive neurologic disease (e.g. multiple sclerosis) or intracranial brain lesions; and history of previous neurosurgery or head trauma that resulted in residual neurologic impairment.

  * Non-cortical disease such as confluence white matter changes (including lacunar infarcts \< 1cm) and asymptomatic, subacute, cerebellar infarcts may be included upon review of a medically responsible neurologist.
* Past or current history of major depression, bipolar disorder or psychotic disorders, or any other major psychiatric condition.
* Contraindication for undergoing MRI or receiving TMS or tACS,
* \>50 mSv of radiation exposure for research within the past year (PET imaging exclusion)
* History of fainting spells of unknown or undetermined etiology that might constitute seizures.
* History of seizures, diagnosis of epilepsy, history of abnormal (epileptiform) EEG or immediate (1st degree relative) family history of epilepsy; with the exception of a single seizure of benign etiology (e.g. febrile seizure) in the judgment of the investigator.
* Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.).
* Metal implants (excluding dental fillings) or devices such as pacemaker, medication pump, nerve stimulator, TENS unit, ventriculo-peritoneal shunt, cochlear implant, unless cleared by the study MD.
* Substance abuse or dependence within the past six months.
* Medications will be reviewed by the responsible MD and a decision about inclusion will be made based on the following: The patient's past medical history, drug dose, history of recent medication changes or duration of treatment, and combination of CNS active drugs.
* All female participants that are pre-menopausal will be required to have a pregnancy test; any participant who is pregnant or breastfeeding will not be enrolled in the study.
* Subjects who, in the investigator's opinion, might not be suitable for the study
* A hair style or head dress that prevents electrode contact with the scalp or would interfere with the stimulation (for example: thick braids, hair weave, afro, wig)

Where this trial is running

Boston, Massachusetts

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Alzheimer DiseaseMild Cognitive Impairment
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.