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Gamma Induction for Alzheimer's Disease

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ClinicalTrials.gov Identifier: NCT03880240
Recruitment Status : Recruiting
First Posted : March 19, 2019
Last Update Posted : September 16, 2020
Sponsor:
Collaborators:
Massachusetts General Hospital
National Institutes of Health (NIH)
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Emiliano Santarnecchi, Beth Israel Deaconess Medical Center

Tracking Information
First Submitted Date  ICMJE March 15, 2019
First Posted Date  ICMJE March 19, 2019
Last Update Posted Date September 16, 2020
Actual Study Start Date  ICMJE August 5, 2019
Estimated Primary Completion Date November 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 1, 2019)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 15, 2019)
  • 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 1, 2019)
  • Follow-up Amyloid PET burden [ Time Frame: up to 16 weeks ]
    Changes in the amyloid load observed via PET imaging at follow-up visits.
  • Follow-up Cognitive Evaluation [ Time Frame: up to 16 weeks ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2019)
  • Follow-up Amyloid PET burden [ Time Frame: up to 16 weeks ]
    Changes in the amyloid load observed via PET imaging at follow-up visits.
  • Follow-up Cognitive Evaluation [ Time Frame: up to 16 weeks ]
    Changes in ADAS-Cog score at follow-up visits
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gamma Induction for Alzheimer's Disease
Official Title  ICMJE Gamma Induction for Amyloid Clearance 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. 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. Participants will be randomly assigned to a repeat amyloid PET scan at either 2, 4 or 8 weeks after the last scan. The PET imaging studies will be conducted at Massachusetts General Hospital.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Alzheimer Disease
  • Mild Cognitive Impairment
Intervention  ICMJE
  • Device: Transcranial Alternating Current Stimulation (tACS)
    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.
    Other Name: Non-invasive Brain Stimulation
  • Other: Sham Transcranial Alternating Current Stimulation
    Placebo Control, simulation of transcranial alternating current stimulation without receiving any stimulation
Study Arms  ICMJE
  • Experimental: 2 weeks of daily tACS sessions
    10 daily (Monday-Friday) 1-hour sessions of tACS stimulation
    Intervention: Device: Transcranial Alternating Current Stimulation (tACS)
  • Experimental: 4 weeks of daily tACS sessions
    20 daily (Monday-Friday) 1-hour sessions of tACS stimulation
    Intervention: Device: Transcranial Alternating Current Stimulation (tACS)
  • Experimental: 4 weeks of twice daily tACS sessions
    20 days (Monday-Friday) of 1-hour sessions of tACS twice per day
    Intervention: Device: Transcranial Alternating Current Stimulation (tACS)
  • Sham Comparator: 2/4 weeks of Sham tACS sessions
    10/20 days (Monday-Friday) of 1-hour sessions of tACS once/twice per day
    Intervention: Other: Sham Transcranial Alternating Current Stimulation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 15, 2019)
55
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2023
Estimated Primary Completion Date November 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
  • 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

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 (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)
  • 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)
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: Nainika Grover 617-667-0362 ngrover@bidmc.harvard.edu
Contact: Molly O'Reilly, MA 617-667-0249 moreilly@bidmc.harvard.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03880240
Other Study ID Numbers  ICMJE 2019P000092
R01AG060981 ( U.S. NIH Grant/Contract )
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
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
  • Massachusetts General Hospital
  • National Institutes of Health (NIH)
  • National Institute on Aging (NIA)
Investigators  ICMJE
Principal Investigator: Emiliano Santarnecchi, PhD Beth Israel Deaconess Medical Center
PRS Account Beth Israel Deaconess Medical Center
Verification Date September 2020

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