Effect of Modulating Gamma Oscillations Using tACS

NCT03412604 | Completed Results DMC FDA Device

• 1 other identifier: 2017P000648
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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 patients with AD.

Conditions

Alzheimer Disease

Keywords

Alzheimer Disease

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  up to 12 weeks

Secondary Outcomes (2)

• PET Microglia Activation

  up to 12 weeks

• Changes in Brain Perfusion as Measured by Arterial Spin Labeling

  6 weeks (pre-post tACS intervention)

Other Outcomes (1)

• Alzheimer's Disease Assessment Scale -Cog Score

  up to 12 weeks

Study Arms (1)

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.

Device: Transcranial Alternating Current Stimulation (tACS)

Interventions

Transcranial Alternating Current Stimulation (tACS) DEVICE

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.

Also known as: Non-invasive Brain Stimulation

tACS

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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,
• Presence of the Thr/Thr polymorphism in the TSPO gene (rs6971) due to low affinity binding for the PBR 28 (microlgia) PET scan
• 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.
• 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)

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Defense Advanced Research Projects Agency: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• 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.

  PMID: 34930421 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Results Point of Contact

• Title: Emiliano Santarnecchi
• Organization: Massachusetts General Hospital

esantarnecchi@mgh.harvard.edu

617-667-0326

Study Officials

• Emiliano Santarnecchi, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Radiology

Study Record Dates

• First Submitted: January 22, 2018
• First Posted: January 26, 2018
• Study Start: August 2, 2018
• Primary Completion: May 7, 2019
• Study Completion: September 15, 2019
• Last Updated: August 22, 2022
• Results First Posted: May 21, 2021

Record last verified: 2022-08

Locations

US (1)