Study on Safety, Feasibility and Neural Activation of Non-Invasive Light Therapy System

Study Overview
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Brief Summary
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Induction of neural oscillations by flickering light is a well established method used for diagnostic of various neural diseases. Recent studies in mice have shown promising results indicating that induction of gamma oscillation at 40 Hz leads to a reduction in amyloid-β and tau in mice models of Alzheimer's disease. This study will use flickering light to induce 40 Hz gamma oscillation as the previously mentioned studies. In the study subject will be exposed to invisible spectral flickering light (active setting) or continuous non-flickering white light (sham setting) for 1 hour each day. The sham setting is a high quality sham intervention as subjects will be blinded to the setting, both appears as white light. As this is the first trial, the focus will be on 1) safety of the intervention 2) feasibility of the proposed intervention time and method 3) indication of efficacy. In stage 1 of the trial 4 age-matched subjects with no Alzheimer's disease will be recruited and be exposed for 1 week. In stage 2 10 patients with Alzheimer's disease will be recruited and exposed for 6 consecutive weeks.

Detailed Description
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Induction of neural oscillations by flickering light is a well established method used for diagnostic of various neural diseases (5,6). Recent studies in mice have shown promising results indicating that induction of gamma oscillation at 40 Hz leads to a reduction in amyloid-β an tau in mice models of Alzheimer's disease (1-4). This study will use flickering light to induce 40 Hz gamma oscillation as the previously mentioned studies. This study will utilize a novel way of masking the light by alternating the spectral composition of a white light, rendering the flicker invisible to the conscience perception while still entraining 40 Hz oscillations in the brain. In the study subject will be exposed to invisible spectral flickering light (active setting) or continuous non-flickering white light (sham setting) for 1 hour each day. The sham setting is a high quality sham intervention as subjects will be blinded to the setting, both appears as white light. As this is the first trial, the focus will be on 1) safety of the intervention 2) feasibility of the proposed intervention time and method 3) indication of efficacy. In stage 1 of the trial 4 age-matched subjects with no Alzheimer's disease will be recruited and be exposed for 1 week. In stage 2 10 patients with Alzheimer's disease will be recruited and exposed for 6 consecutive weeks. Following the 6 weeks of intervention the subject will have 6 weeks of no intevention and assesed agian.

Official Title
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ALZLIGHT Pilot: Study on Safety, Feasibility and Neural Activation of Non-Invasive Light Therapy System

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Other: Light Therapy System (LTS): Active setting
* Other: Light Therapy System (LTS): Sham setting


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult competent persons able to understand the nature of the study and give written informed consent. Stage I: Healthy elderly subject. Stage II: Diagnosed with probable mild to moderate AD based on NIA-AA diagnostic criteria. Age >55 years and <80 years. Females must be post-menopausal. Fluent in Danish > 8 year of normal school education Pass a colour-blindness test (Ishihara colour test) Have visual and auditory capabilities, and language skills necessary for neuropsychological testing. Furthermore, subjects must have a person, hereafter named designated caregiver, who is available to the participant and can provide the necessary assistance with using the LTS device and Actigraph wearable at home and can assist with clinic visits and other practical issues. Exclusion Criteria: Profound visual impairment provided correction with spectacles, if needed. Significant abnormalities related to important parts of the brain e.g. the visual system, pre-frontal cortex or hippocampus, or relevant lesions detected by MRI. Prior history of significant diseases related to the visual system or the brain. Medication Any patient using antiepileptic drugs, neuromodulating drugs or high dose of sedatives will be excluded. Prior history of substance abuse within the past 2 years. Any significant systemic illness or unstable medical condition, which could lead to difficulty complying with the protocol.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Exposure to LTS device set to 40 Hz invisible spectral flicker for 1 hour a day for consecutive days | Other: Light Therapy System (LTS): Active setting<br>* Exposure for 1 hour á day for consecutive days.<br>|
| Sham Comparator: Sham<br>Exposure to LTS device set to continues color matched white light for 1 hour a day for consecutive days | Other: Light Therapy System (LTS): Sham setting<br>* Exposure for 1 hour á day for consecutive days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage I: Feasibility / Compliance assesment | • The compliance of the LTS intervention will be measured by the amount of time (in minutes) of device use per day. | After 1 week of intervention | 
| Stage I: Usability Assessment: | • Usability report on use of device during intervention in the subject's home based on device speciffic questionnaire / structured interviews | After 1 week of intervention | 
| Stage I: Safety Assessment. Evaluation of Adverse Events related to the LTS intervention. | • Safety assessment will be done by collection of all types of adverse events and categorization into severity and relationship to LTS treatment. | After 1 week of intervention | 
| Stage II: Feasibility / Compliance assesment | • The compliance of the LTS intervention will be measured by the amount of time (in minutes) of device use per day. | After 6 weeks of intervention and subsequent 6 weeks of no intervention | 
| Stage II: Safety Assessment. Evaluation of Adverse Events related to the LTS intervention. | • Device- and procedure-related adverse events (DR/PR-AEs) including serious AEs (SAEs) occurring at any time during the trial | After 6 weeks of intervention and subsequent 6 weeks of no intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage II: Induction of gamma ocsillations | • The effect of the LTS intervention will be measured by the amount of 40 Hz SSVEP response during treatment | Changes from baseline to 6 and 12 weeks | 
| Stage II: Connectivity meassures in resting-state functional MRI | • rs-fMRI Connectivity: Change from baseline in correlations between cortical regions at 6 weeks | Changes from baseline to 6 and 12 weeks | 
| Stage II: Connectivity meassures in EEG | • EEG Connectivity: Change from baseline in correlations between cortical regions at 6 weeks | Changes from baseline to 6 and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gamma induction, Gamma entrainment, 40 Hz, Invisible Spectral Flicker, LED, Light Therapy, Brain stimulation, Gamma oscillations