Closed-Loop Neuromodulation for Alzheimer's Disease

Overseen By Joan Camprodon, MD, MPH, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Disqualifiers: Cancer, Cardiovascular disease, Stroke, others

Compensation: Varies

Number of Visits: 1

Duration: 1 session (30 minutes)

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist people with mild cognitive impairment, often due to Alzheimer's or similar dementia. It uses a device called tACS (transcranial alternating current stimulation), which sends tiny electrical currents to the brain to see if it can improve brain rhythms and enhance thinking skills. Participants will complete tasks and fill out questionnaires during the study. Individuals with mild memory problems potentially linked to Alzheimer's, who do not have other major health issues, may be suitable for this trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could improve future treatments for cognitive impairment.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this tACS device is safe for patients with mild cognitive impairment?

Research has shown that transcranial alternating current stimulation (tACS) is generally well-tolerated by people with mild cognitive impairment (MCI) and Alzheimer's disease. One study found that tACS is safe and acceptable, with some positive effects and consistent changes in brain function. Another study is currently underway to further explore the safety and effectiveness of tACS.

While the initial safety results are encouraging, the effectiveness and safety of 40 Hz gamma tACS remain not fully understood. Although no major safety issues have emerged so far, more detailed information is still being gathered to confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using the tACS device for Alzheimer's disease because it offers a new approach to enhancing brain function. Unlike current treatments, which typically rely on medications to manage symptoms, this device uses transcranial alternating current stimulation to modulate brain activity directly. This method could potentially improve memory and cognitive functions by synchronizing brain waves, offering a non-invasive and drug-free alternative. By targeting the brain's electrical activity, tACS might provide benefits that existing drug therapies can't, sparking hope for more effective management of Alzheimer's symptoms.

What evidence suggests that this tACS device is effective for Alzheimer's disease?

Research shows that transcranial alternating current stimulation (tACS) might improve thinking and memory in people with Alzheimer's disease. In this trial, participants with mild cognitive impairment (MCI) will receive tACS, while healthy controls will receive a placebo. Studies have found that tACS, especially at a frequency of 40 Hz, can enhance memory and thinking skills in those with mild cognitive impairment and Alzheimer's. This treatment stimulates brain activity, potentially aiding the brain's natural rhythms. Early findings also suggest that tACS might reduce amyloid deposits, which are linked to Alzheimer's. While these results are promising, further research is needed to fully understand the effects. ^{3 6 7 8 9}

Who Is on the Research Team?

Joan Camprodon, MD, PhD, MPH

Principal Investigator

MGH, Division of Neuropsychiatry and Neuromodulation

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 50-80 with mild cognitive impairment likely due to Alzheimer's, supported by AD biomarkers. It excludes those with brain lesions, acute medical conditions like cancer or heart failure, active major organ disorders, long-term substance abuse history, and contraindications to tACS such as scalp lesions or seizure history.

Inclusion Criteria

I have mild memory problems likely due to Alzheimer's, confirmed by tests.

I am between 50 and 80 years old.

I am a native English speaker.

Exclusion Criteria

I have a diagnosed brain lesion, such as a tumor.

I do not have any worsening or uncontrolled health conditions.

I have an active blood, kidney, lung, hormone, or liver disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive closed-loop transcranial alternating current stimulation (tACS) and undergo EEG, questionnaires, and computer tasks

1 session (30 minutes)

1 visit (in-person)

Follow-up

Participants are monitored for changes in cognitive performance and gamma power after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• tACS device

Trial Overview The study tests closed-loop transcranial alternating current stimulation (tACS) on patients with Alzheimer's-related mild cognitive impairment. It aims to see if tACS can synchronize natural brain rhythms and improve cognition. Participants will have EEGs and complete tasks during visits in this placebo-controlled study.

How Is the Trial Designed?

Group I: MCI Subjects Experimental Treatment 1 Intervention

Group II: Healthy Controls Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Transcranial alternating current stimulation (tACS) shows promise in improving cognitive functioning in older adults, with 7 out of 9 studies on cognitively intact individuals reporting cognitive improvements after stimulation.

However, there is significant variability in study methodologies and outcomes, highlighting the need for standardized protocols and a better understanding of how tACS affects different populations, particularly regarding dosing and physiological effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of tACS Effects on Cognitive Functioning in Older Adults Across the Healthy to Dementia Spectrum. Kraft, JD., Hampstead, BM.[2023]

Transcranial alternating current stimulation (tACS) is a promising neurological intervention that can modulate perception, cognition, and consciousness by influencing oscillating neural activity.

tACS has unique advantages, such as the ability to entrain large groups of neurons and provide precise control over effects, making it a valuable tool for studying the neural basis of cognitive functions, but best practices must be followed for effective application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Alternating Current Stimulation (tACS) Mechanisms and Protocols. Tavakoli, AV., Yun, K.[2020]

Transcranial alternating current stimulation (tACS) has shown promising effects in improving cognitive and memory processes in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), suggesting its potential as a therapeutic tool.

While tACS appears to enhance brain function and cognition, further research is needed to fully understand its effects on the underlying pathophysiology of MCI and AD, as well as its long-term efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of gamma transcranial alternating current stimulation (tACS) on cognitive and memory processes in patients with mild cognitive impairment or Alzheimer's disease: A literature review. Nissim, NR., Pham, DVH., Poddar, T., et al.[2023]

Transcranial direct current stimulation (tDCS) is generally considered safe, with most adverse effects being mild and temporary; however, some cases of persistent skin lesions and rare instances of mania or hypomania have been reported, particularly in patients with depression.

Transcranial alternating current stimulation (tACS) has fewer reported adverse events, and no persistent effects have been documented, but more research is needed to fully establish its safety compared to tDCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of tDCS and tACS: A review. Matsumoto, H., Ugawa, Y.[2020]

In a study involving 20 participants with mild cognitive impairment due to Alzheimer's disease, γ-tACS significantly improved memory performance, as shown by increased scores on the Rey auditory verbal learning test and face-name associations, compared to sham stimulation.

The γ-tACS also enhanced cholinergic transmission, indicated by increased short latency afferent inhibition measured with TMS, suggesting a potential mechanism for its memory-enhancing effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure to gamma tACS in Alzheimer's disease: A randomized, double-blind, sham-controlled, crossover, pilot study. Benussi, A., Cantoni, V., Cotelli, MS., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11712744/

Efficacy of Transcranial Alternating Current Stimulation ... Preliminary evidence suggests the potential efficacy of tACS for improving cognition in Alzheimer's disease patients. However, due to the limited number of ...

2. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.087903

Efficacy of Transcranial Alternating Current Stimulation (tACS ... Preliminary evidence suggests the potential efficacy of tACS for improving cognition in Alzheimer's disease patients. However, due to the ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7158579/

TRanscranial AlterNating current Stimulation FOR patients ... This trial will evaluate the efficacy and safety of 40 Hz tACS in patients with AD, and further explore the potential mechanisms by analyzing amyloid deposits ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X23017412

The impact of gamma transcranial alternating current ... The application of gamma tACS has shown promising results in the improvement of cognitive and memory processes that are impacted in patients with MCI/AD. These ...

5. translationalneurodegeneration.biomedcentral.com translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-024-00423-y

Transcranial alternating current stimulation (tACS) at ... Gamma tACS significantly improved performance in higher-level cognitive functions, in contrast to tDCS, although both induced changes in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11210106/

Transcranial alternating current stimulation (tACS) at gamma ... We outline the current knowledge concerning the clinical efficacy, safety, ease-of-use and cost-effectiveness of tACS on early and advanced AD.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05544201

Transcranial Alternating Current Stimulation (TACS) for ... Significance: This study aims to investigate the feasibility, safety and efficacy of HD-tACS and HD-tDCS over left DLPFC for sleep disturbances and cognitive ...

8. alzres.biomedcentral.com alzres.biomedcentral.com/articles/10.1186/s13195-024-01570-0

TRanscranial AlterNating current stimulation FOR patients ... Our data indicating good safety and acceptability, together with positive results for some outcomes and consistent change in neurophysiological ...

9. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/13872877241289397

The safety and effectiveness of 40 Hz γ-tACS in ... Background. The efficacy and safety of 40 Hz gamma transcranial alternating current stimulation (γ-tACS) in Alzheimer's disease (AD) are still uncertain.