Alzheimer DiseaseNCT03412604
Effect of Modulating Gamma Oscillations Using tACS
A study testing Transcranial Alternating Current Stimulation (tACS) in people with Alzheimer Disease, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This study aims to implement an intervention based on multiple, individualized multifocal tACS stimulation sessions based on individual PET and MRI information in patients with amyloid-positive PET with the hope that this leads to microglia activation and decrease in cerebral amyloid and tau depositions in human… Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Transcranial Alternating Current Stimulation (tACS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Aug 2018to 15 Sep 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 mild to moderate AD*
- Mini Mental State Examination (MMSE) > 18
- Mild AD ≥ 21
- Moderate AD 18-20
- 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.
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- 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
- IQ> 85 as determined by the WTAR and 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, 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)
- Presence of the Thr/Thr polymorphism in the TSPO gene (rs6971) due to low affinity binding for the PBR 28 (microlgia) PET scan
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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: Effect of Modulating Gamma Oscillations by Transcranial Alternating Current Stimulation on Brain Structure and Function in Humans
This study aims to implement an intervention based on multiple, individualized multifocal tACS stimulation sessions based on individual PET and MRI information in patients with amyloid-positive PET with the hope that this leads to microglia activation and decrease in cerebral amyloid and tau depositions in human patients with AD.
Read the detailed description
This study will leverage all this accumulated knowledge by implementing an intervention based on multiple, individualized multifocal tACS stimulation sessions based on individual PET and MRI information in patients with amyloid-positive PET with the hope that this leads to microglia activation and decrease in cerebral amyloid and tau depositions in human patients with AD.This would have immense translational impact, as gamma tACS is an intervention that is portable, does not require expensive hardware, can be widely applied to large numbers of patients with AD, as well as, given its favorable side effect profile, even to patients at earlier stages of the disease who have cerebral amyloid/tau without clinical symptoms.
The investigators aim to enroll 10 individuals with AD with evidence of increased cerebral amyloid burden on amyloid PET imaging. This would allow for a final sample size of 5-6 fully evaluable subjects. Each subject's participation in this study will consist of approximately 31-35 visits: 1 day for consent and screening procedures, 5-7 days of baseline procedures (this includes the PET scans), 20 tACS study visits, and 5-7 days of follow-up assessments. Subjects will undergo baseline cognitive assessment, structural and functional MRI characterization, PET imaging to assess amyloid burden, tau deposition and level of microglia activation, and resting-state EEG measurement. Additionally, subjects will undergo a TMS-EEG and a tACS-EEG recording session to assess brain plasticity levels and identify markers of response to stimulation. All subjects will subsequently undergo 20 sessions of gamma-frequency (40 Hz) tACS. At the end of the 20 sessions, subjects will then repeat the baseline assessments over 5-7 visits, including repeat PET imaging to assess for changes in amyloid burden, tau deposition, and microglia activation.
- Conditions
- Alzheimer Disease
- Being tested
- Transcranial Alternating Current Stimulation (tACS)
- Keywords
- Alzheimer Disease
- Medical subject headings
- Alzheimer Disease
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 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.
| Study group | Role | What they receive |
|---|---|---|
| tACS | Experimental | Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 20 sessions on consecutive weekdays. The tACS intervention (20 sessions) will be preceded and followed by amyloid, microglia and tau PET imaging as well as a clinical/cognitive evaluation. The assessment of the effect of stimulation on microglia activation, amyloid deposition and tau deposition will constitute a primary outcome measure. Assessment of adverse effects will be also evaluated as a secondary outcome. The effect of brain stimulation on brain connectivity will be assessed by EEG and MRI and cognitive function. Receives: Device: Transcranial Alternating Current Stimulation (tACS) |
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 20 tACS sessions. The metric used is standardized uptake value ratio (SUVR), a measure of the amount of proteins in the brain identified at the PET exam. We will calculate the difference between pre and post tACS SUVR for the entire brain and report the average value (and standard deviation) for the entire group of patients. A negative value express a decrease in the amount of proteins in the brain post tACS intervention.
Measured: baseline and up to 12 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 20 tACS sessions. The metric used is SUVR, a measure of the amount of proteins in the brain identified at the PET exam. We will calculate the difference between pre and post tACS SUVR (dSUVR) for the entire brain and report the average value (and standard deviation) for the entire group of patients. A negative value express a decrease in the amount of proteins in the brain post tACS intervention.
Measured: up to 12 weeks
Secondary outcomes (2)
PET Microglia Activation
Changes in the microglia activation observed via PET imaging will be evaluated by comparing PET data acquired before and after the 20 tACS sessions. The metric used is SUVR, a measure of the amount of proteins in the brain identified at the PET exam. We will calculate the difference between pre and post tACS SUVR (dSUVR) for the entire brain and report the average value (and standard deviation) for the entire group of patients. A negative value express a decrease in the amount of proteins in the brain post tACS intervention.
Measured: up to 12 weeks
Changes in Brain Perfusion as Measured by Arterial Spin Labeling
Patients underwent a comprehensive MRI exam before and after the tACS intervention, including measures of brain perfusion via Arterial Spin Labeling (ASL) sequences. The outcome measure represent the average change in perfusion (i.e. blood flow) recorded in regions targeted by tACS. Since Alzheimer's Disease is also characterized by a decrease of brain metabolism, an increased of blood flow after treatment would constitute a very promising sign of tACS efficacy in reducing Alzheimer's pathology in the brain.
We will report the change in blood flow (mean, standard deviation) after tACS treatment.
Measured: 6 weeks (pre-post tACS intervention)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2018
- Study start2 Aug 2018
- Primary completion7 May 2019
- Study completion15 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Defense Advanced Research Projects Agency
- 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
- NCT03412604
- Sponsor's protocol ID
- 2017P000648
- Status last verified
- Aug 2022
- First submitted
- 22 Jan 2018
- Last updated
- 22 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
Sprugnoli G, Munsch F, Cappon D, Paciorek R, Macone J, Connor A, El Fakhri G, Salvador R, Ruffini G, Donohoe K, Shafi MM, Press D, Alsop DC, Pascual Leone A, Santarnecchi E. Impact of multisession 40Hz tACS on hippocampal perfusion in patients with Alzheimer's disease. Alzheimers Res Ther. 2021 Dec 20;13(1):203. doi: 10.1186/s13195-021-00922-4.
PubMed 34930421
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Modulating Gamma Oscillations by Transcranial Alternating Current Stimulation on Brain Structure and Function in Humans
- ClinicalTrials.gov ID
- NCT03412604
- Acronym / sponsor ID
- 2017P000648
- Conditions
- Alzheimer Disease
- Keywords
- Alzheimer Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Defense Advanced Research Projects Agency
- Study start
- 2 Aug 2018 (actual)
- Primary completion
- 7 May 2019 (actual)
- Study completion
- 15 Sep 2019 (actual)
- First posted
- 26 Jan 2018 (actual)
- Results
- Posted 21 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to implement an intervention based on multiple, individualized multifocal tACS stimulation sessions based on individual PET and MRI information in patients with amyloid-positive PET with the hope that this leads to microglia activation and decrease in cerebral amyloid and tau depositions in human patients with AD.
Detailed description
This study will leverage all this accumulated knowledge by implementing an intervention based on multiple, individualized multifocal tACS stimulation sessions based on individual PET and MRI information in patients with amyloid-positive PET with the hope that this leads to microglia activation and decrease in cerebral amyloid and tau depositions in human patients with AD.This would have immense translational impact, as gamma tACS is an intervention that is portable, does not require expensive hardware, can be widely applied to large numbers of patients with AD, as well as, given its favorable side effect profile, even to patients at earlier stages of the disease who have cerebral amyloid/tau without clinical symptoms.
The investigators aim to enroll 10 individuals with AD with evidence of increased cerebral amyloid burden on amyloid PET imaging. This would allow for a final sample size of 5-6 fully evaluable subjects. Each subject's participation in this study will consist of approximately 31-35 visits: 1 day for consent and screening procedures, 5-7 days of baseline procedures (this includes the PET scans), 20 tACS study visits, and 5-7 days of follow-up assessments. Subjects will undergo baseline cognitive assessment, structural and functional MRI characterization, PET imaging to assess amyloid burden, tau deposition and level of microglia activation, and resting-state EEG measurement. Additionally, subjects will undergo a TMS-EEG and a tACS-EEG recording session to assess brain plasticity levels and identify markers of response to stimulation. All subjects will subsequently undergo 20 sessions of gamma-frequency (40 Hz) tACS. At the end of the 20 sessions, subjects will then repeat the baseline assessments over 5-7 visits, including repeat PET imaging to assess for changes in amyloid burden, tau deposition, and microglia activation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| tACS | Experimental | Device: Transcranial Alternating Current Stimulation (tACS)Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 20 sessions on consecutive weekdays. The tACS intervention (20 sessions) will be preceded and followed by amyloid, microglia and tau PET imaging as well as a clinical/cognitive evaluation. The assessment of the effect of stimulation on microglia activation, amyloid deposition and tau deposition will constitute a primary outcome measure. Assessment of adverse effects will be also evaluated as a secondary outcome. The effect of brain stimulation on brain connectivity will be assessed by EEG and MRI and cognitive function. |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Clinical Diagnosis of mild to moderate AD*
- Mini Mental State Examination (MMSE) > 18
- Mild AD ≥ 21
- Moderate AD 18-20
- Demonstration or history of memory impairments.
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, 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 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 | tACS |
Primary outcome
PET Amyloid Burden
Time frame: baseline and up to 12 weeks
Changes in the amyloid load observed via PET imaging will be evaluated by comparing PET data acquired before and after the 20 tACS sessions. The metric used is standardized uptake value ratio (SUVR), a measure of the amount of proteins in the brain identified at the PET exam. We will calculate the difference between pre and post tACS SUVR for the entire brain and report the average value (and standard deviation) for the entire group of patients. A negative value express a decrease in the amount of proteins in the brain post tACS intervention.
PET Tau Deposition
Time frame: up to 12 weeks
Changes in the tau deposition observed via PET imaging will be evaluated by comparing PET data acquired before and after the 20 tACS sessions. The metric used is SUVR, a measure of the amount of proteins in the brain identified at the PET exam. We will calculate the difference between pre and post tACS SUVR (dSUVR) for the entire brain and report the average value (and standard deviation) for the entire group of patients. A negative value express a decrease in the amount of proteins in the brain post tACS intervention.
2 secondary outcomes
PET Microglia Activation
Time frame: up to 12 weeks
Changes in Brain Perfusion as Measured by Arterial Spin Labeling
Time frame: 6 weeks (pre-post tACS intervention)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34930421Sprugnoli G, Munsch F, Cappon D, Paciorek R, Macone J, Connor A, El Fakhri G, Salvador R, Ruffini G, Donohoe K, Shafi MM, Press D, Alsop DC, Pascual Leone A, Santarnecchi E. Impact of multisession 40Hz tACS on hippocampal perfusion in patients with Alzheimer's disease. Alzheimers Res Ther. 2021 Dec 20;13(1):203. doi: 10.1186/s13195-021-00922-4.
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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 study testing Transcranial Alternating Current Stimulation (tACS) in people with Alzheimer Disease, 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 11 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 22 Aug 2022. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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: baseline and up to 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03412604, which also lists 1 linked publication.
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 22 Aug 2022.