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| Name | Class |
|---|---|
| Technical University of Denmark | OTHER |
| University of Copenhagen | OTHER |
| OptoCeutics | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active | Experimental | Exposure to LTS device set to 40 Hz invisible spectral flicker for 1 hour a day for consecutive days |
|
| Sham | Sham Comparator | Exposure to LTS device set to continues color matched white light for 1 hour a day for consecutive days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Light Therapy System (LTS): Active setting | Other | Exposure for 1 hour á day for consecutive days. |
|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Stage II: Changes in cognition: | • Changes in cognition meassured by the ADAS Cog Plus EF & FA neuropsychological test. Score from 0 to 200 | Changes from baseline to 6 and 12 weeks |
| Stage II: Changes in cognition: |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Zealand University DK34197393 | Roskilde | Region Sjælland | 4000 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31076275 | Background | Adaikkan C, Middleton SJ, Marco A, Pao PC, Mathys H, Kim DN, Gao F, Young JZ, Suk HJ, Boyden ES, McHugh TJ, Tsai LH. Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection. Neuron. 2019 Jun 5;102(5):929-943.e8. doi: 10.1016/j.neuron.2019.04.011. Epub 2019 May 7. | |
| 31836315 | Background |
| Label | URL |
|---|---|
| Carstensen M et al. 40 Hz invisible spectral flicker and its potential use in Alzheimer's light therapy treatment. Proc. SPIE 11221, Mechanisms of Photobiomodulation Therapy XV, 112210L (11 March 2020) | View source |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| Light Therapy System (LTS): Sham setting | Other | Exposure for 1 hour á day for consecutive days. |
|
• 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 |
• Changes in cognition meassured by the Trailmaking A&B score from 0 to 1200 seconds
| Changes from baseline to 6 and 12 weeks |
| Stage II: Changes MR spectroscopy | • Chance from baseline in brain metabolism at 6 weeks | Changes from baseline to 6 and 12 weeks |
| Stage II: Changes MR Perfusion | • Chance from baseline in perfusion meassured by Arterial Spin Labelling at 6 weeks | Changes from baseline to 6 and 12 weeks |
| Stage II: Changes MR volumemetry | • Chance from baseline in structural volume of neural structures at 6 weeks | Changes from baseline to 6 and 12 weeks |
| Stage II: Changes in Sleep Quality: | • Actigraphy: To assess changes in sleep patterns | Changes from baseline to 6 and 12 weeks |
| Stage II: EEG spectral features: | • rs-EEG fourier power: To assess changes in spectral features | Changes from baseline to 6 and 12 weeks |
| Adaikkan C, Tsai LH. Gamma Entrainment: Impact on Neurocircuits, Glia, and Therapeutic Opportunities. Trends Neurosci. 2020 Jan;43(1):24-41. doi: 10.1016/j.tins.2019.11.001. Epub 2019 Dec 10. |
| 27929004 | Background | Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, Gillingham TZ, Mathys H, Seo J, Kritskiy O, Abdurrob F, Adaikkan C, Canter RG, Rueda R, Brown EN, Boyden ES, Tsai LH. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 2016 Dec 7;540(7632):230-235. doi: 10.1038/nature20587. |
| 30879788 | Background | Martorell AJ, Paulson AL, Suk HJ, Abdurrob F, Drummond GT, Guan W, Young JZ, Kim DN, Kritskiy O, Barker SJ, Mangena V, Prince SM, Brown EN, Chung K, Boyden ES, Singer AC, Tsai LH. Multi-sensory Gamma Stimulation Ameliorates Alzheimer's-Associated Pathology and Improves Cognition. Cell. 2019 Apr 4;177(2):256-271.e22. doi: 10.1016/j.cell.2019.02.014. Epub 2019 Mar 14. |
| 11355381 | Background | Herrmann CS. Human EEG responses to 1-100 Hz flicker: resonance phenomena in visual cortex and their potential correlation to cognitive phenomena. Exp Brain Res. 2001 Apr;137(3-4):346-53. doi: 10.1007/s002210100682. |
| 22091642 | Background | Kasteleijn-Nolst Trenite D, Rubboli G, Hirsch E, Martins da Silva A, Seri S, Wilkins A, Parra J, Covanis A, Elia M, Capovilla G, Stephani U, Harding G. Methodology of photic stimulation revisited: updated European algorithm for visual stimulation in the EEG laboratory. Epilepsia. 2012 Jan;53(1):16-24. doi: 10.1111/j.1528-1167.2011.03319.x. Epub 2011 Nov 16. |
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |