Transdermal Trigeminal Electrical Neuromodulation on Mild Cognitive Impairment With Insomnia

Study Overview
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Brief Summary
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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 .

Detailed Description
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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.

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

Conditions
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Insomnia, Alzheimer Disease, Mild Cognitive Impairment, Amyloid

Intervention / Treatment
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* Device: Transdermal trigeminal electrical neuromodulation(Cefaly)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amyloid positive mild cognitive impairment+ BDNF met carrier<br>Transdermal trigeminal electrical modulation for 3 months | Device: Transdermal trigeminal electrical neuromodulation(Cefaly)<br>* 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<br>|
| Experimental: Amyloid positive mild cognitive impairment+ BDNF Val/Val<br>Transdermal trigeminal electrical modulation for 3 months | Device: Transdermal trigeminal electrical neuromodulation(Cefaly)<br>* 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<br>|
| Experimental: Amyloid negative mild cognitive impairment+ BDNF met carrier<br>Transdermal trigeminal electrical modulation for 3 months | Device: Transdermal trigeminal electrical neuromodulation(Cefaly)<br>* 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<br>|
| Experimental: Amyloid negative mild cognitive impairment+ BDNF Val/Val<br>Transdermal trigeminal electrical modulation for 3 months | Device: Transdermal trigeminal electrical neuromodulation(Cefaly)<br>* 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<br>|

What is the study measuring?
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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 |