Transdermal Trigeminal Electrical Neuromodulation on Mild Cognitive Impairment With Insomnia

Safety and Effects of Cefaly on Mild Cognitive Impairment With Insomnia and Exploration of Structural and Functional Connectivity Changes

This study aims to validate the safety and impact of transdermal trigeminal electrical neuromodulation(Cefaly) on mild cognitive impairment patients with insomnia on brain functional and structural connectivity as well as sleep parameters evidenced by polysomnography and sleep surveys, with consideration for amyloid positivity and brain-derived neurotrophic factor .

Study Overview

• Status: Recruiting
• Conditions: Insomnia; Alzheimer Disease; Mild Cognitive Impairment; Amyloid
• Intervention / Treatment: Device: Transdermal trigeminal electrical neuromodulation(Cefaly)

Detailed Description

This study aims to validate the safety and impact of transdermal trigeminal electrical neuromodulation(Cefaly) on mild cognitive impairment patients with insomnia on brain functional and structural connectivity as well as sleep parameters evidenced by polysomnography and sleep surveys, with consideration for amyloid positivity and brain-derived neurotrophic factor . A 3-month intervention with transdermal trigeminal electrical neuromodulation will be implemented and sleep surveys, polysomnography and brain MRI will be attained both at baseline and post-intervention.

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

Contacts and Locations

• Study Contact: Name: Yoo Hyun Um; Phone Number: +821063759332; Email: cherubic712@naver.com

Study Locations

• Korea, Republic of
  • Suwon, Korea, Republic of
    • Recruiting
    • St.Vincent's Hospital, the Catholic University of Korea
    • Contact: Se-Min Choung; Phone Number: 82-31-249-8459; Email: semin9137@cmcnu.or.kr
    • Principal Investigator: Yoo Hyun Um, MD, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed with mild cognitive impairment by modified Peterson's criteria
• Identified as amyloid positive by amyloid PET result
• Insomnia severity index of more than 15 or diagnosed with insomnia disorder by Diagnostic Statistical Manual-5

Exclusion Criteria:

• Subjects with active psychiatric or neurological disorders
• Unstable medical conditions (Myocardial infarction, cerebral infarction, congestive heart failures etc.)
• Moderate to severe obstructive sleep apnea (apnea hypopnea index of more than 15), rapid eye movement disorder, narcolepsy
• On regular hypnotic medication (can enroll if there was 2-week wash out period)
• Currently receiving or having a past history of cognitive behavioral therapy for insomnia
• Patients who received transcranial magnetic stimulation (TMS), transcranial direct current stimulation, within 2 weeks before enrollment
• Who are on cognitive enhancers (choline alfoscerate, acetylcarnitine, acetylcholinesterase inhibitors, NMDA receptor antagonist)
• History of cerebral infarction or Parkinson's disease
• History of facial or brain trauma
• A subject with allergy to acrylic acid
• A subject who is sensitive to electrical devices
• A subject who are uncooperative to MRI process

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amyloid positive mild cognitive impairment+ BDNF met carrier; Transdermal trigeminal electrical modulation for 3 months	Device: Transdermal trigeminal electrical neuromodulation(Cefaly); The Cefaly device delivers electrical micro-impulses through a self-adhesive electrode which is placed over the participant's forehead, where the supratrochlear and supraorbital branches of the ophthalmic division of the trigeminal nerve are located. Rectangular, biphasic impulses with an electrical mean equal to zero are transmitted. The impulse width is 250μs, frequency is 60Hz, and the maximum intensity of 16mA is over 14 minutes
Experimental: Amyloid positive mild cognitive impairment+ BDNF Val/Val; Transdermal trigeminal electrical modulation for 3 months	Device: Transdermal trigeminal electrical neuromodulation(Cefaly); The Cefaly device delivers electrical micro-impulses through a self-adhesive electrode which is placed over the participant's forehead, where the supratrochlear and supraorbital branches of the ophthalmic division of the trigeminal nerve are located. Rectangular, biphasic impulses with an electrical mean equal to zero are transmitted. The impulse width is 250μs, frequency is 60Hz, and the maximum intensity of 16mA is over 14 minutes
Experimental: Amyloid negative mild cognitive impairment+ BDNF met carrier; Transdermal trigeminal electrical modulation for 3 months	Device: Transdermal trigeminal electrical neuromodulation(Cefaly); The Cefaly device delivers electrical micro-impulses through a self-adhesive electrode which is placed over the participant's forehead, where the supratrochlear and supraorbital branches of the ophthalmic division of the trigeminal nerve are located. Rectangular, biphasic impulses with an electrical mean equal to zero are transmitted. The impulse width is 250μs, frequency is 60Hz, and the maximum intensity of 16mA is over 14 minutes
Experimental: Amyloid negative mild cognitive impairment+ BDNF Val/Val; Transdermal trigeminal electrical modulation for 3 months	Device: Transdermal trigeminal electrical neuromodulation(Cefaly); The Cefaly device delivers electrical micro-impulses through a self-adhesive electrode which is placed over the participant's forehead, where the supratrochlear and supraorbital branches of the ophthalmic division of the trigeminal nerve are located. Rectangular, biphasic impulses with an electrical mean equal to zero are transmitted. The impulse width is 250μs, frequency is 60Hz, and the maximum intensity of 16mA is over 14 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from Baseline Pittsburgh sleep quality index(PSQI) at 3 months	PSQI global score of more than 5 signifies major sleep disturbance, higher scores suggesting greater sleep disturbance	Post 3-month intervention
Changes from Baseline Insomnia severity index(ISI) at 3 months	ISI is a brief, self-rated scale that is widely used to measure insomnia severity. With seven items scored on a 0-4 scale, it only takes about 5 minutes to complete and scores of 15 or more indicates insomnia of moderate to severe severity	Post 3-month intervention
Changes from Baseline Epworth sleepiness scale(ESS) at 3 months	ESS is a self-administered scale with eight questionnaires measuring sleepiness in daily life. Score of more than 10 signifies clinically meaningful daytime sleepiness, with higher scores indicating more severe sleepiness.	Post-3 month intervention
Changes from Baseline Total time in bed(TIB) at 3 months	One of polysomnography measures	Post 3-month intervention
Changes from Baseline Total sleep time(TST) at 3 months	One of polysomnography measures	Post 3-month intervention
Changes from Baseline Sleep efficiency(SE) at 3 months	One of polysomnography measures	Post 3-month intervention
Changes from Baseline Proportion of stage 1 sleep(N1, %) at 3 months	One of polysomnography measures	Post 3-month intervention
Changes from Baseline Proportion of stage 2 sleep(N2, %) at 3 months	One of polysomnography measures	Post 3-month intervention
Changes from Baseline Proportion of stage 3 sleep(N3, %) at 3 months	One of polysomnography measures	Post 3-month intervention
Changes from Baseline Proportion of REM sleep(R, %) at 3 months	One of polysomnography measures	Post 3-month intervention
Changes from Baseline REM sleep latency(REML) at 3 months	One of polysomnography measures	Post 3-month intervention
Changes from Baseline Sleep latency(SL) at 3 months	One of polysomnography measures	Post 3-month intervention
Changes from Baseline Apnea-hypopnea index(AHI) at 3 months	One of polysomnography measures	Post 3-month intervention
Changes from Baseline Limb movement index(LMI) at 3 months	One of polysomnography measures	Post 3-month intervention
Changes from Baseline Periodic limb movement index(PLMI) at 3 months	One of polysomnography measures	Post 3-month intervention
Changes from Baseline Cortical thickness changes at 3 months	One of neuroimaging measures	Post 3-month intervention
Changes from Baseline Functional connectivity measure at 3 months	One of neuroimaging measures	Post 3-month intervention
Changes from Baseline Fractional anisotropy at 3 months	One of neuroimaging measures	Post 3-month intervention
Changes from Baseline Mean diffusivity at 3 months	One of neuroimaging measures	Post 3-month intervention
Changes from Baseline Verbal fluency at 3 months	One of cognitive measures(subtest of CERAD-K)	Post 3-month intervention
Changes from Baseline Boston naming test at 3 months	One of cognitive measures(subtest of CERAD-K)	Post 3-month intervention
Changes from Baseline Mini-mental status examination at 3 months	One of cognitive measures(subtest of CERAD-K)	Post 3-month intervention
Changes from Baseline Word list recall at 3 months	One of cognitive measures(subtest of CERAD-K)	Post 3-month intervention
Changes from Baseline Word list recognition at 3 months	One of cognitive measures(subtest of CERAD-K)	Post 3-month intervention
Changes from Baseline Constructional recall at 3 months	One of cognitive measures(subtest of CERAD-K)	Post 3-month intervention

Collaborators and Investigators

• Sponsor: Saint Vincent's Hospital, Korea
• Investigators: Principal Investigator: Yoo Hyun Um, St.Vincent's Hospital, College of Medicine, Catholic University of Korea

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2021
• Primary Completion (Estimated): November 30, 2023
• Study Completion (Estimated): November 30, 2023

Study Registration Dates

• First Submitted: December 5, 2021
• First Submitted That Met QC Criteria: January 7, 2022
• First Posted (Actual): January 21, 2022

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Sleep Initiation and Maintenance Disorders; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: VC21DNSI0029

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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