Gamma Induction for Alzheimer's Disease

NCT03880240 | Completed Phase 1 DMC FDA Device

• 2 other identifiers: 2019P000092R01AG060981
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer Disease; Mild Cognitive Impairment

Keywords

Alzheimer Disease; Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (5)

• PET amyloid burden

  Changes in the amyloid load observed via PET imaging will be evaluated by comparing PET data acquired before and after the tACS sessions

  up to 16 weeks

• PET tau deposition

  Changes in the tau deposition observed via PET imaging will be evaluated by comparing PET data acquired before and after the tACS sessions

  up to 16 weeks

• Incidence of Treatment-Emergent Adverse Events

  Adverse Events as a result of tACS stimulation will be reported

  up to 16 weeks

• Change in Gamma activity

  Changes in oscillatory activity in the EEG gamma band will be evaluated before and after the tACS sessions.

  up to 16 weeks

• Alzheimer's Disease Assessment Scale -Cog Score

  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.

  up to 16 weeks

Secondary Outcomes (2)

• Follow-up Amyloid PET burden

  up to 16 weeks

• Follow-up Cognitive Evaluation

  up to 16 weeks

Study Arms (4)

2 weeks of daily tACS sessions

EXPERIMENTAL

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

Device: Transcranial Alternating Current Stimulation (tACS)

4 weeks of daily tACS sessions

EXPERIMENTAL

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

Device: Transcranial Alternating Current Stimulation (tACS)

4 weeks of twice daily tACS sessions

EXPERIMENTAL

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

Device: Transcranial Alternating Current Stimulation (tACS)

2/4 weeks of Sham tACS sessions

SHAM COMPARATOR

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

Other: Sham Transcranial Alternating Current Stimulation

Interventions

Sham Transcranial Alternating Current Stimulation OTHER

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

2/4 weeks of Sham tACS sessions

Transcranial Alternating Current Stimulation (tACS) 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.

Also known as: Non-invasive Brain Stimulation

2 weeks of daily tACS sessions; 4 weeks of daily tACS sessions; 4 weeks of twice daily tACS sessions

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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,
• 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.
• 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)

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: collaborator
• National Institutes of Health (NIH): collaborator
• National Institute on Aging (NIA): collaborator
• Massachusetts General Hospital: lead

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Emiliano Santarnecchi, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Radiology

Study Record Dates

• First Submitted: March 15, 2019
• First Posted: March 19, 2019
• Study Start: August 5, 2019
• Primary Completion: November 30, 2024
• Study Completion: November 30, 2024
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

US (1)