Gamma Induction for Alzheimer's Disease

NCT ID: NCT03880240

Last Updated: 2023-12-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-05
• Study Completion Date: 2024-11-30

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. The PET imaging studies will be conducted at Massachusetts General Hospital and up to 5 PET scans will be performed.

Conditions

Alzheimer Disease; Mild Cognitive Impairment

Keywords

Alzheimer Disease; Mild Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

2 weeks of daily tACS sessions

10 daily (Monday-Friday) 1-hour sessions of tACS stimulation

Group Type: EXPERIMENTAL

Transcranial Alternating Current Stimulation (tACS)

Intervention Type: DEVICE

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.

4 weeks of daily tACS sessions

20 daily (Monday-Friday) 1-hour sessions of tACS stimulation

Group Type: EXPERIMENTAL

Transcranial Alternating Current Stimulation (tACS)

Intervention Type: DEVICE

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.

4 weeks of twice daily tACS sessions

20 days (Monday-Friday) of 1-hour sessions of tACS twice per day

Group Type: EXPERIMENTAL

Transcranial Alternating Current Stimulation (tACS)

Intervention Type: DEVICE

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.

2/4 weeks of Sham tACS sessions

10/20 days (Monday-Friday) of 1-hour sessions of tACS once/twice per day

Group Type: SHAM_COMPARATOR

Sham Transcranial Alternating Current Stimulation

Intervention Type: OTHER

Placebo Control, simulation of transcranial alternating current stimulation without receiving any stimulation

Interventions

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.

Intervention Type: DEVICE

Sham Transcranial Alternating Current Stimulation

Placebo Control, simulation of transcranial alternating current stimulation without receiving any stimulation

Intervention Type: OTHER

Other Intervention Names

Non-invasive Brain Stimulation

Eligibility Criteria

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)

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Emiliano Santarnecchi

Associate Professor of Radiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Emiliano Santarnecchi, PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Stacey Monsell

Role: CONTACT

Phone: 617-667-9088

Email: smonsell@bidmc.harvard.edu

Julianne Reilly

Role: CONTACT

Email: jrreilly@mgh.harvard.edu

Facility Contacts

Stacey Monsell

Role: primary

Other Identifiers

R01AG060981

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2019P000092

Identifier Type: -

Identifier Source: org_study_id