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Effect of Modulating Gamma Oscillations Using tACS

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ClinicalTrials.gov Identifier: NCT03412604
Recruitment Status : Recruiting
First Posted : January 26, 2018
Last Update Posted : September 11, 2018
Sponsor:
Collaborators:
Defense Advanced Research Projects Agency
Massachusetts General Hospital
Information provided by (Responsible Party):
Alvaro Pascual-Leone, MD, PhD, Beth Israel Deaconess Medical Center

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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Device: Transcranial Alternating Current Stimulation (tACS) Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Modulating Gamma Oscillations by Transcranial Alternating Current Stimulation on Brain Structure and Function in Humans
Actual Study Start Date : August 2, 2018
Estimated Primary Completion Date : May 15, 2019
Estimated Study Completion Date : May 15, 2019


Arm Intervention/treatment
Experimental: 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.
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.
Other Name: Non-invasive Brain Stimulation




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: Up to 12 weeks ]
    Adverse Events as a result of tACS stimulation will be reported

  2. PET amyloid burden [ Time Frame: 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

  3. 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


Secondary Outcome Measures :
  1. PET Microglia activation [ Time Frame: up to 12 weeks ]
    Changes in the microglia activation observed via PET imaging will be evaluated by comparing PET data acquired before and after the 20 tACS sessions


Other Outcome Measures:
  1. Alzheimer's Disease Assessment Scale -Cog Score [ Time Frame: up to 12 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

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 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
  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03412604


Contacts
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Contact: Alvaro Pascual-Leone, MD 617-667-0203 apleone@bidmc.harvard.edu
Contact: Rachel Paciorek, MA 617-667-9088 rpaciore@bidmc.harvard.edu

Locations
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United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Rachel Paciorek    617-667-9088    rpacioe@bidmc.harvard.edu   
Contact: Joanna Macone, RN    617-667-0353    jmacone@bidmc.harvard.edu   
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Defense Advanced Research Projects Agency
Massachusetts General Hospital

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Responsible Party: Alvaro Pascual-Leone, MD, PhD, Chief, Division of Cognitive Neurology, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT03412604     History of Changes
Other Study ID Numbers: 2017P000648
First Posted: January 26, 2018    Key Record Dates
Last Update Posted: September 11, 2018
Last Verified: September 2018

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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

Keywords provided by Alvaro Pascual-Leone, MD, PhD, Beth Israel Deaconess Medical Center:
Alzheimer Disease

Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders