Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Gamma Induction for 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03880240
Recruitment Status : Not yet recruiting
First Posted : March 19, 2019
Last Update Posted : April 3, 2019
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

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.


Condition or disease Intervention/treatment Phase
Alzheimer Disease Device: Transcranial Alternating Current Stimulation (tACS) Other: Sham Transcranial Alternating Current Stimulation Phase 1 Phase 2

Detailed Description:
This is an interventional, sham controlled, double-blind study in patients with mild to moderate Alzheimer's Disease (AD). The study will enroll approximately 55 individuals with amyloid positive 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: 2 weeks of daily tACS sessions, 4 weeks of daily tACS sessions, 4 weeks of twice daily tACS sessions, or Sham (placebo) tACS sessions. 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 without a significant reduction in amyloid on the follow-up amyloid PET will undergo a repeat scan in 4 weeks. Participants with a significant reduction in amyloid on the follow-up amyloid PET will be randomly assigned to a repeat scan at either 2, 4 or 8 weeks after the last scan. The PET imaging studies will be conducted at Massachusetts General Hospital.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Gamma Induction for Amyloid Clearance in Alzheimer's Disease
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : November 2023


Arm Intervention/treatment
Experimental: 2 weeks of daily tACS sessions
10 daily (Monday-Friday) 1-hour sessions of tACS stimulation
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

Experimental: 4 weeks of daily tACS sessions
20 daily (Monday-Friday) 1-hour sessions of tACS stimulation
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

Experimental: 4 weeks of twice daily tACS sessions
20 days (Monday-Friday) of 1-hour sessions of tACS twice per day
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

Sham Comparator: 2/4 weeks of Sham tACS sessions
10/20 days (Monday-Friday) of 1-hour sessions of tACS once/twice per day
Other: Sham Transcranial Alternating Current Stimulation
Placebo Control, simulation of transcranial alternating current stimulation without receiving any stimulation




Primary Outcome Measures :
  1. 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

  2. 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

  3. Incidence of Treatment-Emergent Adverse Events [ Time Frame: up to 16 weeks ]
    Adverse Events as a result of tACS stimulation will be reported

  4. 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.

  5. 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.



Secondary Outcome Measures :
  1. Follow-up Amyloid PET burden [ Time Frame: up to 16 weeks ]
    Changes in the amyloid load observed via PET imaging at follow-up visits.

  2. 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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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
    • 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)

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): NCT03880240


Contacts
Layout table for location contacts
Contact: Rachel Paciorek, MA 617-667-9088 rpaciore@bidmc.harvard.edu
Contact: Emiliano Santarnecchi, PhD 617-667-0326 esantarn@bidmc.harvard.edu

Locations
Layout table for location information
United States, Massachusetts
Beth Israel Deaconess Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Rachel Paciorek    617-667-9088    rpaciore@bidmc.harvard.edu   
Contact: Molly O'Reilly    617-667-0249    moreill1@bidmc.harvard.edu   
Principal Investigator: Emiliano Santarnecchi, PhD         
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
National Institutes of Health (NIH)
National Institute on Aging (NIA)
Investigators
Layout table for investigator information
Principal Investigator: Emiliano Santarnecchi, PhD Beth Israel Deaconess Medical Center

Layout table for additonal information
Responsible Party: Emiliano Santarnecchi, Assistant Professor of Neurology, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT03880240     History of Changes
Other Study ID Numbers: 2019P000092
R01AG060981 ( U.S. NIH Grant/Contract )
First Posted: March 19, 2019    Key Record Dates
Last Update Posted: April 3, 2019
Last Verified: April 2019

Layout table for additional information
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 Emiliano Santarnecchi, Beth Israel Deaconess Medical Center:
Alzheimer Disease

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