Alzheimer Disease
Conditions
Keywords
Gamma entrainment, 40 Hz, Invisible Spectral Flicker, LED, Light Therapy, Brain stimulation, Gamma oscillations, Gamma induction
Brief summary
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
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.
Interventions
Exposure for 1 hour á day for consecutive days.
Exposure for 1 hour á day for consecutive days.
Sponsors
Technical University of Denmark
University of Copenhagen
OptoCeutics
Zealand University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 80 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage I: Feasibility / Compliance assesment | After 1 week of intervention | • The compliance of the LTS intervention will be measured by the amount of time (in minutes) of device use per day. |
| Stage II: Safety Assessment. Evaluation of Adverse Events related to the LTS intervention. | After 6 weeks of intervention and subsequent 6 weeks of no intervention | • Device- and procedure-related adverse events (DR/PR-AEs) including serious AEs (SAEs) occurring at any time during the trial |
| Stage II: Feasibility / Compliance assesment | After 6 weeks of intervention and subsequent 6 weeks of no intervention | • The compliance of the LTS intervention will be measured by the amount of time (in minutes) of device use per day. |
| Stage I: Safety Assessment. Evaluation of Adverse Events related to the LTS intervention. | After 1 week of intervention | • Safety assessment will be done by collection of all types of adverse events and categorization into severity and relationship to LTS treatment. |
| Stage I: Usability Assessment: | After 1 week of intervention | • Usability report on use of device during intervention in the subject's home based on device speciffic questionnaire / structured interviews |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stage II: Connectivity meassures in resting-state functional MRI | Changes from baseline to 6 and 12 weeks | • rs-fMRI Connectivity: Change from baseline in correlations between cortical regions at 6 weeks |
| Stage II: Induction of gamma ocsillations | Changes from baseline to 6 and 12 weeks | • The effect of the LTS intervention will be measured by the amount of 40 Hz SSVEP response during treatment |
| Stage II: Connectivity meassures in EEG | Changes from baseline to 6 and 12 weeks | • EEG Connectivity: Change from baseline in correlations between cortical regions at 6 weeks |
Other
| Measure | Time frame | Description |
|---|---|---|
| Stage II: Changes MR spectroscopy | Changes from baseline to 6 and 12 weeks | • Chance from baseline in brain metabolism at 6 weeks |
| Stage II: EEG spectral features: | Changes from baseline to 6 and 12 weeks | • rs-EEG fourier power: To assess changes in spectral features |
| Stage II: Changes in Sleep Quality: | Changes from baseline to 6 and 12 weeks | • Actigraphy: To assess changes in sleep patterns |
| Stage II: Changes MR volumemetry | Changes from baseline to 6 and 12 weeks | • Chance from baseline in structural volume of neural structures at 6 weeks |
| Stage II: Changes MR Perfusion | Changes from baseline to 6 and 12 weeks | • Chance from baseline in perfusion meassured by Arterial Spin Labelling at 6 weeks |
| Stage II: Changes in cognition: | Changes from baseline to 6 and 12 weeks | • Changes in cognition meassured by the ADAS Cog Plus EF & FA neuropsychological test. Score from 0 to 200 |
Countries
Denmark
Outcome results
None listed