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

Primary Purpose

Alzheimer Disease

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Light Therapy System (LTS): Active setting
Light Therapy System (LTS): Sham setting
Sponsored by
Zealand University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Alzheimer Disease focused on measuring Gamma entrainment, 40 Hz, Invisible Spectral Flicker, LED, Light Therapy, Brain stimulation, Gamma oscillations, Gamma induction

Eligibility Criteria

55 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Zealand University DK34197393

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Active

Sham

Arm Description

Exposure to LTS device set to 40 Hz invisible spectral flicker for 1 hour a day for consecutive days

Exposure to LTS device set to continues color matched white light for 1 hour a day for consecutive days

Outcomes

Primary Outcome Measures

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.
Stage I: Usability Assessment:
• Usability report on use of device during intervention in the subject's home based on device speciffic questionnaire / structured interviews
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.
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.
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

Secondary Outcome Measures

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
Stage II: Connectivity meassures in resting-state functional MRI
• rs-fMRI Connectivity: Change from baseline in correlations between cortical regions at 6 weeks
Stage II: Connectivity meassures in EEG
• EEG Connectivity: Change from baseline in correlations between cortical regions at 6 weeks

Full Information

First Posted
August 27, 2020
Last Updated
December 12, 2022
Sponsor
Zealand University Hospital
Collaborators
Technical University of Denmark, University of Copenhagen, OptoCeutics
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1. Study Identification

Unique Protocol Identification Number
NCT04574921
Brief Title
Study on Safety, Feasibility and Neural Activation of Non-Invasive Light Therapy System
Acronym
ALZLIGHT Pilot
Official Title
ALZLIGHT Pilot: Study on Safety, Feasibility and Neural Activation of Non-Invasive Light Therapy System
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
October 1, 2020 (Actual)
Primary Completion Date
July 12, 2022 (Actual)
Study Completion Date
July 12, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zealand University Hospital
Collaborators
Technical University of Denmark, University of Copenhagen, OptoCeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease
Keywords
Gamma entrainment, 40 Hz, Invisible Spectral Flicker, LED, Light Therapy, Brain stimulation, Gamma oscillations, Gamma induction

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active
Arm Type
Experimental
Arm Description
Exposure to LTS device set to 40 Hz invisible spectral flicker for 1 hour a day for consecutive days
Arm Title
Sham
Arm Type
Sham Comparator
Arm Description
Exposure to LTS device set to continues color matched white light for 1 hour a day for consecutive days
Intervention Type
Other
Intervention Name(s)
Light Therapy System (LTS): Active setting
Intervention Description
Exposure for 1 hour á day for consecutive days.
Intervention Type
Other
Intervention Name(s)
Light Therapy System (LTS): Sham setting
Intervention Description
Exposure for 1 hour á day for consecutive days.
Primary Outcome Measure Information:
Title
Stage I: Feasibility / Compliance assesment
Description
• The compliance of the LTS intervention will be measured by the amount of time (in minutes) of device use per day.
Time Frame
After 1 week of intervention
Title
Stage I: Usability Assessment:
Description
• Usability report on use of device during intervention in the subject's home based on device speciffic questionnaire / structured interviews
Time Frame
After 1 week of intervention
Title
Stage I: Safety Assessment. Evaluation of Adverse Events related to the LTS intervention.
Description
• Safety assessment will be done by collection of all types of adverse events and categorization into severity and relationship to LTS treatment.
Time Frame
After 1 week of intervention
Title
Stage II: Feasibility / Compliance assesment
Description
• The compliance of the LTS intervention will be measured by the amount of time (in minutes) of device use per day.
Time Frame
After 6 weeks of intervention and subsequent 6 weeks of no intervention
Title
Stage II: Safety Assessment. Evaluation of Adverse Events related to the LTS intervention.
Description
• Device- and procedure-related adverse events (DR/PR-AEs) including serious AEs (SAEs) occurring at any time during the trial
Time Frame
After 6 weeks of intervention and subsequent 6 weeks of no intervention
Secondary Outcome Measure Information:
Title
Stage II: Induction of gamma ocsillations
Description
• The effect of the LTS intervention will be measured by the amount of 40 Hz SSVEP response during treatment
Time Frame
Changes from baseline to 6 and 12 weeks
Title
Stage II: Connectivity meassures in resting-state functional MRI
Description
• rs-fMRI Connectivity: Change from baseline in correlations between cortical regions at 6 weeks
Time Frame
Changes from baseline to 6 and 12 weeks
Title
Stage II: Connectivity meassures in EEG
Description
• EEG Connectivity: Change from baseline in correlations between cortical regions at 6 weeks
Time Frame
Changes from baseline to 6 and 12 weeks
Other Pre-specified Outcome Measures:
Title
Stage II: Changes in cognition:
Description
• Changes in cognition meassured by the ADAS Cog Plus EF & FA neuropsychological test. Score from 0 to 200
Time Frame
Changes from baseline to 6 and 12 weeks
Title
Stage II: Changes in cognition:
Description
• Changes in cognition meassured by the Trailmaking A&B score from 0 to 1200 seconds
Time Frame
Changes from baseline to 6 and 12 weeks
Title
Stage II: Changes MR spectroscopy
Description
• Chance from baseline in brain metabolism at 6 weeks
Time Frame
Changes from baseline to 6 and 12 weeks
Title
Stage II: Changes MR Perfusion
Description
• Chance from baseline in perfusion meassured by Arterial Spin Labelling at 6 weeks
Time Frame
Changes from baseline to 6 and 12 weeks
Title
Stage II: Changes MR volumemetry
Description
• Chance from baseline in structural volume of neural structures at 6 weeks
Time Frame
Changes from baseline to 6 and 12 weeks
Title
Stage II: Changes in Sleep Quality:
Description
• Actigraphy: To assess changes in sleep patterns
Time Frame
Changes from baseline to 6 and 12 weeks
Title
Stage II: EEG spectral features:
Description
• rs-EEG fourier power: To assess changes in spectral features
Time Frame
Changes from baseline to 6 and 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Facility Information:
Facility Name
Zealand University DK34197393
City
Roskilde
State/Province
Region Zealand
ZIP/Postal Code
4000
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31076275
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.
Results Reference
background
PubMed Identifier
31836315
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.
Results Reference
background
PubMed Identifier
27929004
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.
Results Reference
background
PubMed Identifier
30879788
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.
Results Reference
background
PubMed Identifier
11355381
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.
Results Reference
background
PubMed Identifier
22091642
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.
Results Reference
background
Links:
URL
https://doi.org/10.1117/12.2544338
Description
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)

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

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