Gamma Induction for Alzheimer's Disease

Alzheimer Disease Clinical Trial

Official title:

Gamma Induction for Amyloid Clearance in Alzheimer's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03880240
• Other study ID #: 2019P000092
• Secondary ID: R01AG060981
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 5, 2019
• Est. completion date: November 2024

Study information

• Verified date: December 2023
• Source: Massachusetts General Hospital
• Contact: Stacey Monsell
• Phone: 617-667-9088
• Email: smonsell[@]bidmc.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 55
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

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:
• Sham Transcranial Alternating Current Stimulation
Placebo Control, simulation of transcranial alternating current stimulation without receiving any stimulation

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Beth Israel Deaconess Medical Center, National Institute on Aging (NIA), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Incidence of Treatment-Emergent Adverse Events	Adverse Events as a result of tACS stimulation will be reported	up to 16 weeks
Primary	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
Primary	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	Follow-up Amyloid PET burden	Changes in the amyloid load observed via PET imaging at follow-up visits.	up to 16 weeks
Secondary	Follow-up Cognitive Evaluation	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.	up to 16 weeks