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

NCT ID: NCT04574921

Last Updated: 2022-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-01

Study Completion Date

2022-07-12

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Alzheimer Disease

Keywords

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Gamma entrainment 40 Hz Invisible Spectral Flicker LED Light Therapy Brain stimulation Gamma oscillations Gamma induction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Active

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

Group Type EXPERIMENTAL

Light Therapy System (LTS): Active setting

Intervention Type OTHER

Exposure for 1 hour á day for consecutive days.

Sham

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

Group Type SHAM_COMPARATOR

Light Therapy System (LTS): Sham setting

Intervention Type OTHER

Exposure for 1 hour á day for consecutive days.

Interventions

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Light Therapy System (LTS): Active setting

Exposure for 1 hour á day for consecutive days.

Intervention Type OTHER

Light Therapy System (LTS): Sham setting

Exposure for 1 hour á day for consecutive days.

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

55 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Technical University of Denmark

OTHER

Sponsor Role collaborator

University of Copenhagen

OTHER

Sponsor Role collaborator

OptoCeutics

INDUSTRY

Sponsor Role collaborator

Zealand University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Zealand University DK34197393

Roskilde, Region Sjælland, Denmark

Site Status

Countries

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Denmark

References

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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.

Reference Type BACKGROUND
PMID: 31076275 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31836315 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27929004 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30879788 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11355381 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22091642 (View on PubMed)

Related Links

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https://doi.org/10.1117/12.2544338

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)

Other Identifiers

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REG-085-2020

Identifier Type: -

Identifier Source: org_study_id