Transcranial Electrical Stimulation for Mild Cognitive Impairment

Recruiting at 1 trial location

Overseen By Phan Luu, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Brain Electrophysiology Laboratory Company

Must not be taking: EEG affecting drugs

Disqualifiers: Seizures, Epilepsy, Brain injury, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn about the ability of non-invasive brain stimulation during sleep to enhance people's deep sleep and its potential benefit on memory in people with mild cognitive impairment via home use sleep therapy device (SleepWISP) as well as learn about biomarkers associated with Alzheimer disease (AD). The clinical trial aims to answer the following main questions: 1. Whether the non-invasive transcranial electrical stimulation (TES) delivered by SleepWISP could provide short-term enhancement of deep sleep in a single night in the target population. 2. Whether TES delivered by SleepWISP could enhance deep sleep over multiple nights in the target population. 3. Whether enhance on deep sleep could improve memory performance in the target population. Participants will be asked to wear non-invasive and painless devices that record their brain activity during sleep along with an actigraphy watch that measures their movement throughout the day. In addition, blood samples or nasal swab assays will be collected from participants multiple times during the study.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those on medications that may affect the EEG (a test that measures brain activity). It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment SleepWISP for Mild Cognitive Impairment?

Research shows that transcranial electrical stimulation (TES) can enhance deep sleep and improve memory in people with mild cognitive impairment (MCI). Studies found that TES increased sleep-related brain activity and improved memory performance, suggesting it may help with memory issues in MCI. ^{1 2 3 4 5}

Is transcranial electrical stimulation safe for humans?

Transcranial electrical stimulation (tES) is generally considered safe for humans when used according to tested and accepted protocols. No serious adverse events have been reported in over 18,000 sessions, and mild side effects like headaches or skin sensations are rare. Devices should be responsibly manufactured and used within established guidelines to ensure safety. ^{4 6 7 8 9}

How does the SleepWISP treatment differ from other treatments for mild cognitive impairment?

The SleepWISP treatment is unique because it uses non-invasive transcranial electrical stimulation (TES) during sleep to enhance deep sleep and improve memory, targeting specific brain areas associated with sleep oscillations. This approach is different from other treatments as it focuses on modulating sleep patterns to potentially slow the progression of cognitive decline. ^{1 2 3 4 6}

Eligibility Criteria

This trial is for adults aged 40-80 without MCI and those aged 55-85 with Amnestic MCI. It's not suitable for individuals on certain medications, with allergies to lidocaine or silver, history of seizures or ECT, severe insomnia or sleep apnea, severe anxiety or depression, metal in the head, pregnancy, adverse reaction to TMS, brain injury/trauma, significant neurological diseases like Parkinson's or stroke.

Inclusion Criteria

I am between 55 and 85 years old with Amnestic MCI.

I am a healthy volunteer aged between 40 and 80.

Exclusion Criteria

I have had a brain injury or surgery in the past.

I have had a stroke in the past.

I have undergone Electroconvulsive Therapy (ECT).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I: Baseline and Acclimation

Participants use the Sleep WISP device to passively record sleep EEG without TES as baseline, followed by a randomized experiment condition (placebo or active TES) and a final session with the opposite condition.

2 weeks

3 visits (in-person)

Phase II: Repeated-Measures Placebo-Controlled

Participants wear the WISP device for 2 weeks with either sham or treatment TES, followed by a 2-week washout period, and then receive the remaining condition for the last 2 weeks.

6 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including memory performance and biomarker analysis.

4 weeks

Treatment Details

Interventions

• SleepWISP

Trial Overview The study tests if a home-use device called SleepWISP can improve deep sleep and memory in people with mild cognitive impairment using transcranial electrical stimulation (TES). Participants will wear devices that monitor brain activity during sleep and an actigraphy watch by day. Blood samples will also be collected.

Participant Groups

Group I: Deep Sleep Enhancement with TES Experimental Treatment 1 Intervention

Transcranial Electrical Stimulation, 0.5 Hz sine wave, 0.5 mA, between frontal (frontopolar and inferior lateral frontal) and posterior (mastoid and occipital) electrodes.

Who Is Running the Clinical Trial?

Brain Electrophysiology Laboratory Company

Lead Sponsor

Trials

4

Recruited

130+

Wake Forest University

Collaborator

Trials

193

Recruited

151,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

Transcranial Electrical Stimulation (TES) targeting anterior limbic areas significantly increased the duration of deep sleep (N3) in 13 healthy adults, suggesting a potential method to enhance sleep quality.

The study also found that TES increased spectral power in specific brain regions, indicating that this stimulation may improve neurological health and memory, which could be beneficial for individuals at risk of Alzheimer's Disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Electrical Stimulation targeting limbic cortex increases the duration of human deep sleep. Hathaway, E., Morgan, K., Carson, M., et al.[2021]

In a study involving 16 patients with mild cognitive impairment (MCI), slow oscillatory transcranial direct current stimulation (so-tDCS) applied during daytime naps significantly enhanced sleep-related brain activity, specifically increasing slow oscillations and spindle power, which are important for memory formation.

The so-tDCS not only improved the synchronization of these brain activities but also led to better visual declarative memory performance compared to sham stimulation, suggesting a promising noninvasive approach to address sleep and memory issues in early Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Promoting Sleep Oscillations and Their Functional Coupling by Transcranial Stimulation Enhances Memory Consolidation in Mild Cognitive Impairment. Ladenbauer, J., Ladenbauer, J., Külzow, N., et al.[2020]

Short duration repetitive transcranial electrical stimulation (SDR-tES) during daytime naps significantly enhances declarative memory consolidation in healthy individuals, showing improved memory performance compared to sham stimulation both immediately after sleep and 48 hours later.

SDR-tES also increases the amount of time spent in deeper NREM sleep (NREM3) and boosts the rate of slow oscillations during NREM sleep, suggesting that the timing of stimulation during quiet brain activity may optimize its effects on memory consolidation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short Duration Repetitive Transcranial Electrical Stimulation During Sleep Enhances Declarative Memory of Facts. Cellini, N., Shimizu, RE., Connolly, PM., et al.[2023]

Transcranial Electrical Stimulation (tES) has been shown to modify brain oscillations during sleep, indicating its potential as a non-invasive tool for sleep modulation.

While the effects of tES on objective sleep patterns are inconsistent, subjective assessments of sleep quality consistently show improvements, suggesting that tES may enhance perceived sleep quality in both healthy individuals and patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Transcranial Electrical Stimulation of the Brain on Sleep: A Systematic Review. Dondé, C., Brunelin, J., Micoulaud-Franchi, JA., et al.[2021]

Acoustic stimulation during sleep significantly increased slow-wave activity (SWA) by over 10% in individuals with amnestic mild cognitive impairment (aMCI), indicating its potential to enhance sleep quality.

While the increase in SWA was associated with improved memory recall in some participants, consistent memory improvement may require longer or more intense stimulation, as only five out of nine patients showed enhanced recall after stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acoustic enhancement of sleep slow oscillations in mild cognitive impairment. Papalambros, NA., Weintraub, S., Chen, T., et al.[2023]

Low-intensity transcranial electric stimulation (tES) is considered safe when following established protocols and using devices that adhere to engineering risk-management standards, but outcomes can vary significantly based on numerous factors such as dosage and individual characteristics.

Self-administered brain stimulation devices must be designed to minimize variability in efficacy and should not make medical claims, as they are less regulated than medical devices, highlighting the importance of ethical marketing practices by manufacturers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive brain stimulation and neuroenhancement. Antal, A., Luber, B., Brem, AK., et al.[2022]

Transcranial electrical stimulation (tES), including tDCS and MHF-tPCS, was found to be well tolerated in healthy subjects over a six-week period, with common side effects being mild skin sensations like tingling and itching, which were less frequent than in the sham-tDCS group.

The MHF-tPCS group showed significantly higher compliance in completing sessions compared to the sham-tDCS group, indicating that this waveform may be more acceptable for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of Repeated Application of Transcranial Electrical Stimulation with Limited Outputs to Healthy Subjects. Paneri, B., Adair, D., Thomas, C., et al.[2018]

Low intensity transcranial electrical stimulation (TES) is considered safe, with no serious adverse events reported in over 18,000 sessions across various populations, including healthy individuals and patients with neurological or psychiatric conditions.

While moderate adverse events like skin burns from tDCS are rare, mild adverse events such as headaches and fatigue are more common, and the safety profile is consistent across different age groups and vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Antal, A., Alekseichuk, I., Bikson, M., et al.[2023]

Limited output transcranial electrical stimulation (tES) devices, such as tDCS, tACS, and tPCS, have been shown to have electrical output levels significantly lower than many FDA-cleared devices, suggesting they pose minimal risk when responsibly manufactured and marketed.

The paper establishes a comprehensive framework for the regulation and manufacturing standards of low-power tES devices, promoting safety and innovation while ensuring public access to these technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited output transcranial electrical stimulation (LOTES-2017): Engineering principles, regulatory statutes, and industry standards for wellness, over-the-counter, or prescription devices with low risk. Bikson, M., Paneri, B., Mourdoukoutas, A., et al.[2018]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Transcranial Electrical Stimulation targeting limbic cortex increases the duration of human deep sleep. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Promoting Sleep Oscillations and Their Functional Coupling by Transcranial Stimulation Enhances Memory Consolidation in Mild Cognitive Impairment. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Short Duration Repetitive Transcranial Electrical Stimulation During Sleep Enhances Declarative Memory of Facts. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The Effects of Transcranial Electrical Stimulation of the Brain on Sleep: A Systematic Review. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Acoustic enhancement of sleep slow oscillations in mild cognitive impairment. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Non-invasive brain stimulation and neuroenhancement. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Tolerability of Repeated Application of Transcranial Electrical Stimulation with Limited Outputs to Healthy Subjects. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Limited output transcranial electrical stimulation (LOTES-2017): Engineering principles, regulatory statutes, and industry standards for wellness, over-the-counter, or prescription devices with low risk. [2018]