Clinical trial NCT04574921: Study on Safety, Feasibility and Neural Activation of Non-Invasive Light Therapy System
Official title: ALZLIGHT Pilot: Study on Safety, Feasibility and Neural Activation of Non-Invasive Light Therapy System
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alzheimer Disease
Keywords: Gamma entrainment
40 Hz
Invisible Spectral Flicker
LED
Light Therapy
Brain stimulation
Gamma oscillations
Gamma induction
Lead sponsor: Zealand University Hospital
Sponsor class: OTHER
Collaborators: name: Technical University of Denmark
name: University of Copenhagen
name: OptoCeutics
First posted: 2020-10-05
Enrollment: 16
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Stage I: Feasibility / Compliance assesment
timeFrame: After 1 week of intervention
measure: Stage I: Usability Assessment:
timeFrame: After 1 week of intervention
measure: Stage I: Safety Assessment. Evaluation of Adverse Events related to the LTS intervention.
timeFrame: After 1 week of intervention
measure: Stage II: Feasibility / Compliance assesment
timeFrame: After 6 weeks of intervention and subsequent 6 weeks of no intervention
measure: Stage II: Safety Assessment. Evaluation of Adverse Events related to the LTS intervention.
timeFrame: After 6 weeks of intervention and subsequent 6 weeks of no intervention
Secondary outcomes:
measure: Stage II: Induction of gamma ocsillations
timeFrame: Changes from baseline to 6 and 12 weeks
measure: Stage II: Connectivity meassures in resting-state functional MRI
timeFrame: Changes from baseline to 6 and 12 weeks
measure: Stage II: Connectivity meassures in EEG
timeFrame: Changes from baseline to 6 and 12 weeks
Other outcomes:
measure: Stage II: Changes in cognition:
timeFrame: Changes from baseline to 6 and 12 weeks
measure: Stage II: Changes in cognition:
timeFrame: Changes from baseline to 6 and 12 weeks
measure: Stage II: Changes MR spectroscopy
timeFrame: Changes from baseline to 6 and 12 weeks
measure: Stage II: Changes MR Perfusion
timeFrame: Changes from baseline to 6 and 12 weeks
measure: Stage II: Changes MR volumemetry
timeFrame: Changes from baseline to 6 and 12 weeks
measure: Stage II: Changes in Sleep Quality:
timeFrame: Changes from baseline to 6 and 12 weeks
measure: Stage II: EEG spectral features:
timeFrame: Changes from baseline to 6 and 12 weeks
Locations:
city: Roskilde
country: Denmark
facility: Zealand University DK34197393
state: Region Zealand
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
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citation: 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.
citation: 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.