Study on the Effect of 40 Hz Non-Invasive Light Therapy System

NCT ID: NCT05260177

Last Updated: 2024-01-24

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

RECRUITING

Clinical Phase

NA

Total Enrollment

62 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-20

Study Completion Date

2026-12-01

Brief Summary

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The ALZLIGHT STAGE III Study is a continuation of the ALZLIGHT Pilot - Study on Safety, Feasibility and Neural Activation of Non-Invasive Light Therapy System. As with the first two stages, this study will examine whether entrainment of 40 Hz neural oscillation by novel 40 Hz Invisible Spectral Flicker is a potential therapy for Alzheimer's Disease. In order to examine this, 62 patients with mild to moderate Alzheimer's Disease will be recruited. The patients will be exposed to the Non-Invasive Light Therapy System for 1 hour a day for 6 months. The effect will be measured by a combination of electroencephalography, cognitive testing, functional magnetic resonance imaging, magnetic resonance spectroscopy and actigraphy.

Detailed Description

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Recent studies in mouse models of Alzhimer's Disease (AD) have shown that exposure to 40 Hz stroboscopic light therapy for one hour a day, resulted in slowing disease progression and lead to multiple neuroprotective effects such as cognition and memory recovery, and even scavenged both tau and Aβ protein species. Hence, the 40 Hz stroboscopic light therapy has a considerable potential for treatment of humans.

This study will utilize a novel way of masked 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, 62 patients with probable mild to moderate AD will be exposed to either invisible spectral flickering light through the Light Therapy System (LTS) (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 appear as white light.

The study will last 8½ months for each participant and consist of 3 periods: Enrollment period of 1 month, an intervention period of 6 months, and a 1½ month post-interventional follow-up period.

In order to test whether the LTS intervention is a potential treatment for AD, cognition will be measured by neuropsychological tests at baseline and at follow-ups. To get a better understanding of the potential effects, markers of efficacy based on MRI, MRS, EEG and blood samples will be tested.

The results from this study will increase the understanding of the impact of gamma oscillations in the human brain, and how it can be utilized as a novel and important tool for the treatment of neurodegenerative diseases.

Conditions

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Alzheimer's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A parallel-group randomized (1:1), double-blinded, placebo-controlled, clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
Double-blinded

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 DEVICE

Exposure for 1 hour á day for consecutive days

Sham

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

Group Type SHAM_COMPARATOR

Light Therapy System (LTS): Sham Setting

Intervention Type DEVICE

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 DEVICE

Light Therapy System (LTS): Sham Setting

Exposure for 1 hour á day for consecutive days

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Adult competent person, able to understand the nature of the study and give written informed consent.
* Diagnosed with probable mild to moderate AD based on NIA-AA diagnostic criteria.
* Age \> 55 years. Females must be post-menopausal.
* Fluent in Danish.
* \> 8 years of normal school education
* Pass a color-blindness test (Ishihara color test)
* Have visual and auditory capabilities, and language skills necessary for neuropsychological testing.
* Participants must have a designated caregiver, who is available to the participant and can provide the necessary assistance with using the LTS device and the Actigraph wearable at home and assist with clinical visits and other practical issues

Exclusion Criteria

* Profound visual impairment (visual acuity \> 0.5) provided correction with spectacles, if needed
* Significant abnormalities related to important parts of the brain, e.g., the visual system, prefrontal cortex, or hippocampus, or relevant lesions detected by pre-trial imaging.
* Prior history of significant diseases related to the visual system or the brain.
* Medication: Use of any 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 (at the discretion of the PI)
Minimum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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OptoCeutics

INDUSTRY

Sponsor Role collaborator

University of Copenhagen

OTHER

Sponsor Role collaborator

Technical University of Denmark

OTHER

Sponsor Role collaborator

Göteborg University

OTHER

Sponsor Role collaborator

Zealand University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Maibritt Horning, MSc

Role: STUDY_CHAIR

Zealand University Hospital, Department of Neurology

Mikkel Pejstrup Agger, MD

Role: STUDY_CHAIR

Zealand Univeristy Hospital, Department of Neurology

Peter Høgh, MD, Phd

Role: PRINCIPAL_INVESTIGATOR

Zealand Univeristy Hospital, Department of Neurology

Locations

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Zealand University Hospital

Roskilde, , Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Peter Høgh, MD, Phd

Role: CONTACT

Maibritt Horning, MSc

Role: CONTACT

+45 81949649

Facility Contacts

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Peter Høgh, MD, Phd

Role: primary

Maibritt Horning, MSc

Role: backup

+4581949649

References

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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)

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)

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)

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)

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)

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)

Alawode DOT, Heslegrave AJ, Ashton NJ, Karikari TK, Simren J, Montoliu-Gaya L, Pannee J, O Connor A, Weston PSJ, Lantero-Rodriguez J, Keshavan A, Snellman A, Gobom J, Paterson RW, Schott JM, Blennow K, Fox NC, Zetterberg H. Transitioning from cerebrospinal fluid to blood tests to facilitate diagnosis and disease monitoring in Alzheimer's disease. J Intern Med. 2021 Sep;290(3):583-601. doi: 10.1111/joim.13332. Epub 2021 Jun 26.

Reference Type BACKGROUND
PMID: 34021943 (View on PubMed)

Benedet AL, Mila-Aloma M, Vrillon A, Ashton NJ, Pascoal TA, Lussier F, Karikari TK, Hourregue C, Cognat E, Dumurgier J, Stevenson J, Rahmouni N, Pallen V, Poltronetti NM, Salvado G, Shekari M, Operto G, Gispert JD, Minguillon C, Fauria K, Kollmorgen G, Suridjan I, Zimmer ER, Zetterberg H, Molinuevo JL, Paquet C, Rosa-Neto P, Blennow K, Suarez-Calvet M; Translational Biomarkers in Aging and Dementia (TRIAD) study, Alzheimer's and Families (ALFA) study, and BioCogBank Paris Lariboisiere cohort. Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum. JAMA Neurol. 2021 Dec 1;78(12):1471-1483. doi: 10.1001/jamaneurol.2021.3671.

Reference Type BACKGROUND
PMID: 34661615 (View on PubMed)

Agger MP, Horning M, Carstensen MS, Danielsen ER, Baandrup AO, Nguyen M, Hogh P, Miskowiak K, Petersen PM, Madsen KH, Kjaer TW. Study on the effect of 40 Hz non-invasive light therapy system. A protocol for a randomized, double-blinded, placebo-controlled clinical trial. Front Aging Neurosci. 2023 Oct 12;15:1250626. doi: 10.3389/fnagi.2023.1250626. eCollection 2023.

Reference Type DERIVED
PMID: 37901795 (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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ASIII

Identifier Type: -

Identifier Source: org_study_id

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