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tACS for Amyloid-β Reduction in Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03290326
Recruitment Status : Completed
First Posted : September 21, 2017
Last Update Posted : August 29, 2019
Information provided by (Responsible Party):
Emiliano Santarnecchi, Beth Israel Deaconess Medical Center

Tracking Information
First Submitted Date  ICMJE September 15, 2017
First Posted Date  ICMJE September 21, 2017
Last Update Posted Date August 29, 2019
Actual Study Start Date  ICMJE November 27, 2017
Actual Primary Completion Date May 14, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 19, 2017)
Incidence of Treatment-Emergent Adverse Events [ Time Frame: Up to six weeks ]
Adverse Events as a result of tACS stimulation will be reported
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03290326 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2017)
  • PET Amyloid burden [ Time Frame: Up to six weeks ]
    Changes in the amyloid load observed via PET imaging will be evaluated by comparing PET data acquired before and after the 10 tACS sessions.
  • EEG gamma-band spectral power [ Time Frame: Up to six weeks ]
    Changes in the spectral power in the low-mid gamma band (35-80Hz) will be measured using electroencephalography (EEG) and reported in term of Pre-Post tACS differences.
  • Adas-Cog score [ Time Frame: Up to six weeks ]
    Change in Adas-Cog score will be reported, to document a potential clinical benefit of tACS.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE tACS for Amyloid-β Reduction in Alzheimer's Disease
Official Title  ICMJE Feasibility and Safety of a High-Frequency Transcranial Alternating Current Stimulation Intervention for Amyloid-β Reduction in Alzheimer's Disease
Brief 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. 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 current study seeks to use a novel therapeutic intervention that uses noninvasive brain stimulation to target amyloid in the brain. The investigators anticipate this will decrease the amyloid levels in the brain, as evidence by Positron Emission Tomography (PET) imaging.
Detailed Description

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. There is no current treatments that alter disease progression.

Investigators will recruit 20 individuals with AD with evidence of amyloid placques in the brain through Positron Emission Tomography (PET) imaging. Investigators will use a novel approach, transcranial alternating current stimulation (tACS), to target the region of maximum amyloid burden in the brain. All participants will receive tACS. Each individual's participation in the study will consist of approximately 16 visits: 3 days for screening/baseline procedures as described below, 10 tACS study visits, and 3 days for follow-up assessments. Subjects will undergo baseline cognitive assessment, structural and functional MRI characterization, and resting-state EEG measurement. Additionally, patients will undergo a tACS-EEG recording session to assess brain plasticity levels and identify markers of response to stimulation. All subjects will then undergo 10 1-hour sessions of gamma-frequency (40 Hz) tACS, targeted to the region of maximal tracer uptake on the amyloid PET study. Subjects will take a standardized adverse effect questionnaire before and after each session and complete a short cognitive test after each session to demonstrate safety and tolerability. At the end of the 10 sessions, subjects will then repeat the baseline assessments, followed by repeat amyloid PET imaging to assess for changes in amyloid burden.

Investigators anticipate that targeting the region of amyloid burden in the brain with tACS will reduce the amyloid burden as evidence by the follow up PET imaging and show improvement on electrophysiological measures of brain function and on cognitive testing. If our prediction is correct, this will will provide a critical first step in the development of a novel intervention to prevent and treat AD.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer Disease
Intervention  ICMJE Device: Transcranial Alternating Current Stimulation (tACS)
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 Arms  ICMJE Experimental: tACS
Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 10 sessions on consecutive weekdays. The tACS intervention (10 sessions) will be preceded and followed by amyloid PET imaging as well as a clinical/cognitive evaluation. The assessment of adverse effects will constitute a Primary outcome measure. Changes in amyloid load in the stimulated brain region will be evaluated and constitute a secondary outcome of the study. Clinically relevant changes in cognitive and clinical scores will be also evaluated as secondary outcomes. Stimulation will be also preceded and followed by electroencephalography (EEG) recording aimed at assessing changes in spectral power in the gamma band.
Intervention: Device: Transcranial Alternating Current Stimulation (tACS)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 27, 2019)
Original Estimated Enrollment  ICMJE
 (submitted: September 19, 2017)
Actual Study Completion Date  ICMJE May 14, 2019
Actual Primary Completion Date May 14, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Clinical Diagnosis of mild AD defined by: Clinical Dementia Rating (CDR) = 0.5-1, Mini Mental State Examination (MMSE) >/= 20, Demonstration or history of memory impairments
  • 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
  • Intelligence Quotient (IQ) > 85 as determined by the Wechsler Test of Adult Reading (WTAR) and 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, 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 Transcranial Magnetic Stimulation (TMS) or tACS,

    • 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, Transcutaneous Electrical 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 Central Nervous System (CNS) active drugs.
  • All female participants that are pre-menopausal will be required to have a pregnancy test; any participant who is pregnant will not be enrolled in the study.
  • BMI > 40 kg/m2. We will limit the BMI to <40 kg/m2 because of weight limits of the scanner bed and width limits of the MRI.
  • 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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 45 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03290326
Other Study ID Numbers  ICMJE 2017P000373
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Emiliano Santarnecchi, Beth Israel Deaconess Medical Center
Study Sponsor  ICMJE Beth Israel Deaconess Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Emiliano Santarnecchi Beth Israel Deaconess Medical Center
PRS Account Beth Israel Deaconess Medical Center
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP