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

Alzheimer Disease Clinical Trial

— ALZLIGHT Pilot  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04574921
• Other study ID #: REG-085-2020
• Status: Completed
• Phase: N/A
• Start date: October 1, 2020
• Est. completion date: July 12, 2022

Study information

• Verified date: December 2022
• Source: Zealand University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: July 12, 2022
• Est. primary completion date: July 12, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Other:
• Light Therapy System (LTS): Active setting
Exposure for 1 hour á day for consecutive days.
• Light Therapy System (LTS): Sham setting
Exposure for 1 hour á day for consecutive days.

Locations

Country	Name	City	State
Denmark	Zealand University DK34197393	Roskilde	Region Zealand

Sponsors (4)

Lead Sponsor	Collaborator
Zealand University Hospital	OptoCeutics, Technical University of Denmark, University of Copenhagen

Country where clinical trial is conducted

Denmark, 

References & Publications (6)

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. — View 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. — View 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. — View 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. Erratum In: Nature. 2018 Oct;562(7725):E1. — View 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Stage II: Changes in cognition:	• Changes in cognition meassured by the Trailmaking A&B score from 0 to 1200 seconds	Changes from baseline to 6 and 12 weeks
Other	Stage II: Changes MR spectroscopy	• Chance from baseline in brain metabolism at 6 weeks	Changes from baseline to 6 and 12 weeks
Other	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
Other	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
Other	Stage II: Changes in Sleep Quality:	• Actigraphy: To assess changes in sleep patterns	Changes from baseline to 6 and 12 weeks
Other	Stage II: EEG spectral features:	• rs-EEG fourier power: To assess changes in spectral features	Changes from baseline to 6 and 12 weeks
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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

External Links

•   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)