Alzheimer DiseasePhase 1/2NCT03880240
Gamma Induction for Alzheimer's Disease
A Phase 1/2 study testing Transcranial Alternating Current Stimulation (tACS) in people with Alzheimer Disease and Mild Cognitive Impairment, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
Alzheimer's Disease (AD) is characterized by amyloid-β (Aβ) plaque buildup and phosphorylated tau (p-tau) in the brain, as well as widespread neurodegeneration. Amyloid-β and tau are proteins that build up in the brain that may contribute to memory problems. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Alzheimer Disease, Mild Cognitive Impairment
- What is being tested?
- Transcranial Alternating Current Stimulation (tACS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Aug 2019to 30 Nov 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Official title: Gamma Induction for Amyloid Clearance in Alzheimer's Disease
Alzheimer's Disease (AD) is characterized by amyloid-β (Aβ) plaque buildup and phosphorylated tau (p-tau) in the brain, as well as widespread neurodegeneration. Amyloid-β and tau are proteins that build up in the brain that may contribute to memory problems. The evidence suggests that both amyloid and tau play a critical role in AD and interventions that reliably and safely decrease the intracerebral burden of amyloid or tau could potentially be of marked clinical importance. Currently, therapeutic options are very limited and while there are pharmacologic interventions that transiently improve cognitive function, there are no treatments that alter disease progression.
The purpose of this study is to see if multiple daily sessions of non-invasive brain stimulation can affect brain activity to decrease the amount of amyloid and tau in people with AD as compared to Sham (placebo) stimulation. The type of brain stimulation that will be used is called transcranial alternating current stimulation (tACS). This study will investigate different doses of tACS (2-4 weeks) and assess safety. The hope is that tACS will decrease the amount of amyloid and tau and improve memory and thinking in people with AD.
Read the detailed description
This is an interventional, sham controlled, double-blind study in patients with early to moderate Alzheimer's Disease (AD). The study will enroll approximately 55 individuals with amyloid positive Mild Cognitive Impairment (MCI) or AD. Each subject will undergo a 1-2 visit screening period consisting of a physical and neurological exam, medical history and medication review, safety questionnaires, and cognitive testing. Each subject will then undergo 5-7 baseline visits including neuropsychological testing (memory and thinking tests), amyloid Positron Emission Tomography (PET) imaging if one is not available or it has been greater than 6 months, tau PET imaging, tACS-EEG (transcranial alternating current stimulation and electroencephalogram) assessment, TMS-EEG (transcranial magnetic stimulation and electroencephalogram) plasticity assessment, functional magnetic resonance imaging (fMRI), blood and saliva sample collection, and optional lumbar puncture (LP). Participants will be randomly assigned to one of four groups: stimulation for 2 weeks or 4 weeks, once a day or twice a day. One of the groups is a sham group. This means that this group will not receive actual tACS. Each session will be one hour of either individualized gamma-frequency (40 Hz) tACS or sham tACS, depending on the assigned group. Subjects will be assessed for any side effects before and after each session and complete a short memory and thinking test either daily or weekly. At the end of the daily sessions, 5-7 follow up visits will include a repeat of the baseline measures including amyloid and tau PET scans. Long-term follow-up visits will include an EEG, cognitive testing and an amyloid PET scan. The PET imaging studies will be conducted at Massachusetts General Hospital and up to 5 PET scans will be performed.
- Conditions
- Alzheimer Disease, Mild Cognitive Impairment
- Being tested
- Transcranial Alternating Current Stimulation (tACS), Sham Transcranial Alternating Current Stimulation
- Keywords
- Alzheimer Disease, Mild Cognitive Impairment
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Alternating Current Stimulation (tACS)Device
Also called Non-invasive Brain Stimulation
tACS is a non-invasive way of stimulating the brain externally using weak electric currents. Electrodes are placed into a cap that you wear on your head. A weak electrical current travels back and forth through the electrodes to your head. tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region.
Sham Transcranial Alternating Current StimulationOther
Placebo Control, simulation of transcranial alternating current stimulation without receiving any stimulation
| Study group | Role | What they receive |
|---|---|---|
| 2 weeks of daily tACS sessions | Experimental | 10 daily (Monday-Friday) 1-hour sessions of tACS stimulation Receives: Device: Transcranial Alternating Current Stimulation (tACS) |
| 4 weeks of daily tACS sessions | Experimental | 20 daily (Monday-Friday) 1-hour sessions of tACS stimulation Receives: Device: Transcranial Alternating Current Stimulation (tACS) |
| 4 weeks of twice daily tACS sessions | Experimental | 20 days (Monday-Friday) of 1-hour sessions of tACS twice per day Receives: Device: Transcranial Alternating Current Stimulation (tACS) |
| 2/4 weeks of Sham tACS sessions | Sham comparator | 10/20 days (Monday-Friday) of 1-hour sessions of tACS once/twice per day Receives: Other: Sham Transcranial Alternating Current Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
PET amyloid burden
Changes in the amyloid load observed via PET imaging will be evaluated by comparing PET data acquired before and after the tACS sessions
Measured: up to 16 weeks
PET tau deposition
Changes in the tau deposition observed via PET imaging will be evaluated by comparing PET data acquired before and after the tACS sessions
Measured: up to 16 weeks
Incidence of Treatment-Emergent Adverse Events
Adverse Events as a result of tACS stimulation will be reported
Measured: up to 16 weeks
Change in Gamma activity
Changes in oscillatory activity in the EEG gamma band will be evaluated before and after the tACS sessions.
Measured: up to 16 weeks
Alzheimer's Disease Assessment Scale -Cog Score
Change in ADAS-Cog score will be reported, to document a potential clinical benefit of tACS. The scale ranges from a total score of 0-70 with higher score indicating greater cognitive impairment.
The ADAS-Cog has a total scoring range of 0-70, with the score based on the number of errors made in each of the 11 following items: word recall task, commands, constructional praxis, naming task, ideational praxis, orientation, word recognition, remembering word recognition test instructions, comprehension of spoken language, word-finding difficulty in spontaneous speech, and spoken language ability. Subscale scores are not reported, only the total score.
Measured: up to 16 weeks
Secondary outcomes (2)
Follow-up Amyloid PET burden
Changes in the amyloid load observed via PET imaging at follow-up visits.
Measured: up to 16 weeks
Follow-up Cognitive Evaluation
Changes in Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) score at follow-up visits
The ADAS-Cog has a total scoring range of 0-70, with the score based on the number of errors made in each of the 11 following items: word recall task, commands, constructional praxis, naming task, ideational praxis, orientation, word recognition, remembering word recognition test instructions, comprehension of spoken language, word-finding difficulty in spontaneous speech, and spoken language ability. Subscale scores are not reported, only the total score.
The scale ranges from a total score of 0-70 with higher score indicating greater cognitive impairment.
Measured: up to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2019
- Study start5 Aug 2019
- Primary completion30 Nov 2024
- Study completion30 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, National Institutes of Health (NIH), National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Emiliano Santarnecchi, Massachusetts General Hospital
- Investigators
- Emiliano Santarnecchi, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03880240
- Sponsor's protocol ID
- 2019P000092
- Other IDs
- R01AG060981
- Status last verified
- Mar 2026
- First submitted
- 15 Mar 2019
- Last updated
- 11 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gamma Induction for Amyloid Clearance in Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT03880240
- Acronym / sponsor ID
- 2019P000092
- Conditions
- Alzheimer Disease, Mild Cognitive Impairment
- Keywords
- Alzheimer Disease, Mild Cognitive Impairment
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, National Institutes of Health (NIH), National Institute on Aging (NIA)
- Study start
- 5 Aug 2019 (actual)
- Primary completion
- 30 Nov 2024 (actual)
- Study completion
- 30 Nov 2024 (actual)
- First posted
- 19 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Alzheimer's Disease (AD) is characterized by amyloid-β (Aβ) plaque buildup and phosphorylated tau (p-tau) in the brain, as well as widespread neurodegeneration. Amyloid-β and tau are proteins that build up in the brain that may contribute to memory problems. The evidence suggests that both amyloid and tau play a critical role in AD and interventions that reliably and safely decrease the intracerebral burden of amyloid or tau could potentially be of marked clinical importance. Currently, therapeutic options are very limited and while there are pharmacologic interventions that transiently improve cognitive function, there are no treatments that alter disease progression.
The purpose of this study is to see if multiple daily sessions of non-invasive brain stimulation can affect brain activity to decrease the amount of amyloid and tau in people with AD as compared to Sham (placebo) stimulation. The type of brain stimulation that will be used is called transcranial alternating current stimulation (tACS). This study will investigate different doses of tACS (2-4 weeks) and assess safety. The hope is that tACS will decrease the amount of amyloid and tau and improve memory and thinking in people with AD.
Detailed description
This is an interventional, sham controlled, double-blind study in patients with early to moderate Alzheimer's Disease (AD). The study will enroll approximately 55 individuals with amyloid positive Mild Cognitive Impairment (MCI) or AD. Each subject will undergo a 1-2 visit screening period consisting of a physical and neurological exam, medical history and medication review, safety questionnaires, and cognitive testing. Each subject will then undergo 5-7 baseline visits including neuropsychological testing (memory and thinking tests), amyloid Positron Emission Tomography (PET) imaging if one is not available or it has been greater than 6 months, tau PET imaging, tACS-EEG (transcranial alternating current stimulation and electroencephalogram) assessment, TMS-EEG (transcranial magnetic stimulation and electroencephalogram) plasticity assessment, functional magnetic resonance imaging (fMRI), blood and saliva sample collection, and optional lumbar puncture (LP). Participants will be randomly assigned to one of four groups: stimulation for 2 weeks or 4 weeks, once a day or twice a day. One of the groups is a sham group. This means that this group will not receive actual tACS. Each session will be one hour of either individualized gamma-frequency (40 Hz) tACS or sham tACS, depending on the assigned group. Subjects will be assessed for any side effects before and after each session and complete a short memory and thinking test either daily or weekly. At the end of the daily sessions, 5-7 follow up visits will include a repeat of the baseline measures including amyloid and tau PET scans. Long-term follow-up visits will include an EEG, cognitive testing and an amyloid PET scan. The PET imaging studies will be conducted at Massachusetts General Hospital and up to 5 PET scans will be performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 2 weeks of daily tACS sessions | Experimental | Device: Transcranial Alternating Current Stimulation (tACS)10 daily (Monday-Friday) 1-hour sessions of tACS stimulation |
| 4 weeks of daily tACS sessions | Experimental | Device: Transcranial Alternating Current Stimulation (tACS)20 daily (Monday-Friday) 1-hour sessions of tACS stimulation |
| 4 weeks of twice daily tACS sessions | Experimental | Device: Transcranial Alternating Current Stimulation (tACS)20 days (Monday-Friday) of 1-hour sessions of tACS twice per day |
| 2/4 weeks of Sham tACS sessions | Sham comparator | Other: Sham Transcranial Alternating Current Stimulation10/20 days (Monday-Friday) of 1-hour sessions of tACS once/twice per day |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Clinical Diagnosis of early to moderate AD*
- 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
Key exclusion criteria (15 listed)
- 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.
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Alternating Current Stimulation (tACS)Also: Non-invasive Brain StimulationtACS is a non-invasive way of stimulating the brain externally using weak electric currents. Electrodes are placed into a cap that you wear on your head. A weak electrical current travels back and forth through the electrodes to your head. tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region. | Device | 2 weeks of daily tACS sessions, 4 weeks of daily tACS sessions, 4 weeks of twice daily tACS sessions |
| Sham Transcranial Alternating Current StimulationPlacebo Control, simulation of transcranial alternating current stimulation without receiving any stimulation | Other | 2/4 weeks of Sham tACS sessions |
Primary outcome
PET amyloid burden
Time frame: up to 16 weeks
Changes in the amyloid load observed via PET imaging will be evaluated by comparing PET data acquired before and after the tACS sessions
PET tau deposition
Time frame: up to 16 weeks
Changes in the tau deposition observed via PET imaging will be evaluated by comparing PET data acquired before and after the tACS sessions
Incidence of Treatment-Emergent Adverse Events
Time frame: up to 16 weeks
Adverse Events as a result of tACS stimulation will be reported
Change in Gamma activity
Time frame: up to 16 weeks
Changes in oscillatory activity in the EEG gamma band will be evaluated before and after the tACS sessions.
Alzheimer's Disease Assessment Scale -Cog Score
Time frame: up to 16 weeks
Change in ADAS-Cog score will be reported, to document a potential clinical benefit of tACS. The scale ranges from a total score of 0-70 with higher score indicating greater cognitive impairment. The ADAS-Cog has a total scoring range of 0-70, with the score based on the number of errors made in each of the 11 following items: word recall task, commands, constructional praxis, naming task, ideational praxis, orientation, word recognition, remembering word recognition test instructions, comprehension of spoken language, word-finding difficulty in spontaneous speech, and spoken language ability. Subscale scores are not reported, only the total score.
2 secondary outcomes
Follow-up Amyloid PET burden
Time frame: up to 16 weeks
Follow-up Cognitive Evaluation
Time frame: up to 16 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emiliano Santarnecchi, PhD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Transcranial Alternating Current Stimulation (tACS) in people with Alzheimer Disease and Mild Cognitive Impairment, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PET amyloid burden (time frame: up to 16 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2026.