Home Sleep Therapy for Older Adults With MCI

Home Sleep Therapy System for Mild Cognitive Impairment

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.

Study Overview

• Status: Recruiting
• Conditions: Sleep; Mild Cognitive Impairment; Machine Learning; Memory; Transcranial Electrical Stimulation
• Intervention / Treatment: Device: Transcranial Electrical Stimulation

Detailed Description

The purpose of the present research is to evaluate the ability of non-invasive transcranial electrical stimulation (TES) during slow-wave sleep (SWS) to enhance this stage of sleep for people with mild cognitive impairment (MCI). A previous study of the investigators have demonstrated, in a pilot study, that TES can acutely (i.e., immediately after TES) increase SWS duration in healthy people. In the present proposal, the investigators aim to replicate and extend the pilot findings in seniors with MCI. It is evidenced that decline in SWS duration with aging is associated for memory impairment in seniors, which also creates risk for Alzheimer disease (AD). At the same time as conducting TES to enhance SWS sleep in seniors with MCI, the investigators also aim to explore changes in biomarkers associated with AD, including Aβ40 and Aβ42.

The investigators propose to conduct a sleep study using the Brain Electrophysiology Laboratory (BEL) company's Sleep WISP device (described in detail below). The Sleep WISP device is made up of three components: 1) 16-channel EEG amplifier with transcranial electrical stimulation (TES) capabilities, 2) a 16-channel EEG headband and 3) a small portable computer.

All participants will be provided a Sleep WISP device. Participation in the study requires that participants use the Sleep WISP when they sleep. As participants sleep, their sleep EEG will be measured and automatically scored by the computer to determine stage of sleep. When SWS is detected, low-level current (.5-1 mA total) will be applied through pre-set electrodes (four on the forehead and four at base of back of head). These electrodes were used in our pilot study, showing that current applied through these electrodes during SWS is able to increase total SWS sleep duration.

To evaluate the efficacy of the system, BEL will use a small, exploratory pilot sample of 10 employees and staff members to run the testing in Eugene, Oregon. After the 10 pilot subjects at BEL with employees and staff and prior to the main study, the protocol and system will be tested with older adults at each of the Wake Forest area (Winston-Salem, North Carolina) and Portland-Eugene surrounding area (Oregon) as pilot sub-studies for device usability feedback with seniors. These pilot subjects will only take part in the acute portion of the parent sleep study, where the first night is acclimation (no TES), the second night is TES or sham, and then a week later, they get TES or sham, for a total of three nights for the pilot studies. This pilot study does not include the PAVL memory test.

The greater study is divided into two phases.

Phase I involves up to nine sleep sessions. The first session is a baseline/acclimation session. In the first session, participants will use the Sleep WISP device to passively record sleep EEG (no TES) as baseline. The second session is performed the night following the baseline session with randomized experiment condition (either placebo or active TES session). Participants will be blinded for what condition they receive. The final session will occur one week after the second session to receive the opposite experiment condition to the second session. In the week between the second and final sessions, participants will be asked to wear the device at night to record their EEG. During this period, there will be no TES stimulation.

Phase II of the study can begin as early as the night following the completion of Phase I. To participate in Phase II participants do not need to have participated in Phase I. Phase II will follow a repeated-measures placebo-controlled design across six weeks. An equal number of participants without MCI (control group) and with MCI (experimental group) will be enrolled. Following screening and thorough training, participants will wear the WISP device for 2 weeks and receive either sham or treatment TES every night. A 2 week washout period where participants do not use the device will follow. Finally, participants will receive the remaining condition (sham or treatment) each night of the last 2 weeks of participation. Participants will also be asked to wear an actigraphy watch that measures sleep parameters based on movement each night in Phase II. A trained phlebotomist will collect blood samples or nasal swab assays from participants before and after each condition (sham and treatment; 4 total measurements) for Aβ detection.

In both Phases I and II, prior to sleep, participants will be presented with a paired-associate verbal learning (PAVL) task. Participants will be required to learn the list of words, to a pre-specified performance criterion. After waking from sleep in the morning, participants will be tested with the same list, to assess retention of the previously learned materials.

In our previous TES study of SWS enhancement, the investigators were able to show that SWS can be enhanced immediately (short-term/acute) after TES. The study was performed in the BEL sleep lab. Phase I of the proposed new study will extend the previous pilot study results by using Sleep WISP device as participants with MCI sleep at home, which will allow us to support home monitoring and acute treatment of disordered sleep for adults with MCI. Phase II will assess whether SWS modulation over multiple nights will produce cumulative enhancement of SWS in adults with MCI. In both study phases, the investigators will also evaluate the cognitive consequences, specifically declarative memory, of enhancing SWS.

Aim 1: Phase I aims to replicate our previous study (acute/short-term enhancement of SWS and safety/feasibility) in seniors with MCI with the sleep WISP device.

Aim 2: Phase II aims to assess the ability of TES to cumulatively enhance SWS over multiple sessions in seniors with MCI compared to healthy controls.

Aim 3: Evaluate SWS quality on a declarative memory task in older adults with MCI.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Don M Tucker, PhD; Phone Number: 541-653-8266; Email: don.tucker@bel.company
• Study Contact Backup: Name: Phan Luu, PhD; Phone Number: 541-653-9797; Email: phan.luu@bel.company

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27109
      • Not yet recruiting
      • Wake Forest University
      • Contact: Ruth Benca, PhD; Email: rbenca@wakehealth.edu
      • Contact: Caitlin Carroll, PhD; Email: cmcarrol@wakehealth.edu
  • Oregon
    • Eugene, Oregon, United States, 97405
      • Recruiting
      • Brain Electrophysiology Laboratory Company
      • Contact: Don M Tucker, PhD; Phone Number: 541-653-8266; Email: don.tucker@bel.company
      • Contact: Phan Luu, PhD; Phone Number: 541-653-9797; Email: phan.luu@bel.company

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• For participant with Amnestic MCI, the inclusion age range is 55-85 years old.
• For healthy volunteers without MCI, the inclusion age range is 40-80 years old.

Exclusion Criteria:

• History of seizures
• History of epilepsy
• History of mod/severe brain injury or trauma (including neurosurgery)
• History or presence of significant neurological disease such as Parkinson
• History of Electroconvulsive Therapy (ECT)
• Presence of severe insomnia
• Presence of untreated sleep apnea
• Presence of severe anxiety or depression
• Medications that may affect the EEG
• History of stroke
• Sensitivity or allergy to lidocaine or silver
• Presence of active suicidal ideation
• Presence of metal in head or implants or medication infusion device
• Pregnancy
• Adverse reaction to TMS

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Deep Sleep Enhancement with TES; Transcranial Electrical Stimulation, 0.5 Hz sine wave, 0.5 mA, between frontal (frontopolar and inferior lateral frontal) and posterior (mastoid and occipital) electrodes.	Device: Transcranial Electrical Stimulation; Oscillating electrical current; Other Names: SleepWISP (Wireless Interface Sensor Pod)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device Usability	Criteria for success: the prototype is safe for all participants, and it is usable at home by 80% of adults with MCI. Specific outcome ratings (5-point Lickert scale) will be obtained for (1) ability to clean the device, (2) ability to apply the device, (3) ability to turn on the tablet (launching the dedicated software); (4) ability to start treatment; (5) ability to complete treatment.	Collected each day they use the Sleep WISP system, for three sessions over 10 days during Phase I of the study.
Duration of N3 Sleep	Duration in minutes of N3 sleep	Measured during the nights of sleep (typically 8 hours) across both phases of the study
Percentage of N3 Sleep	Percentage of the night's sleep spent in N3	Measured during the nights of sleep (typically 8 hours) across both phases of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Memory Performance; Paired-Associates Verbal Learning (PAVL)	10 pairs of unrelated, neutral-valence nouns are learned each night before sleep. Participants are tested in the morning when an online program provides the first word of the pair and they type in the second word that went with it (cued recall). More accurately recalled pairs of words (0-10 pairs) indicates better memory performance.	Measured at the beginning as baseline, then once weekly over the course of study, and then once on the last day of the study, for a total of up to 7 times.
Beck Depression Inventory (BDI)	Assessment of psychiatric symptomatology; 21-item self-reported inventory that measures symptoms of depression. Responses are weighted and a higher score (1-40) indicates higher levels of depression.	Measured at the beginning as baseline, then once weekly over the course of study, and then once on the last day of the study, for a total of up to 7 times.
Beta Amyloid Excretion Blood Sample or Nasal Swab Assay	Collected for exploratory analysis on biomarkers associated with Alzheimer's disease and treated with an anticoagulant, plasma isolated and stored at -80 until Aβ detection. Aβ40 and 42 detection will be performed using a commercially-available immunoassay (Innotest, Fugirebio).	Collected on the first day of Phase II of the study, and then the end of each week in Phase II, for a total of up to 7 times.

Collaborators and Investigators

• Sponsor: Brain Electrophysiology Laboratory Company
• Collaborators: National Institute on Aging (NIA); Wake Forest University

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: February 24, 2023
• First Submitted That Met QC Criteria: March 6, 2023
• First Posted (Actual): March 16, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 14, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Slow Wave Sleep; NREM N3 Sleep
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 1R44AG077965 (U.S. NIH Grant/Contract); 1R44AG077965-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes