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

NCT05260177 | Recruiting DMC

• 1 other identifier: ASIII
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer's Disease

Keywords

Gamma Entrainment; 40 Hz; Invisible Spectral Flicker; LED; Light Therapy; Brain Stimulation; Gamma Oscillations; Gamma Induction

Outcome Measures

Primary Outcomes (2)

• Gamma oscillations assessment

  Determine the total gamma power at 40 Hz, with no concomitant LTS device stimulation, assess changes in the gamma power at 40 Hz.

  Change from Baseline to 6 months

• Induction of 40 Hz Gamma oscillations

  Estimate the change in electrical field patterns by EEG SSVEP, assess the difference between placebo and treatment for power spectral density signal to noise ratio at baseline measured by EEG SSVEP

  Change from Baseline to 6 months

Secondary Outcomes (15)

• Cognition and memory assessment

  Change from Baseline to 6 months and 12 months

• Cognition and memory assessment

  Change from Baseline to 6 months and 12 months

• Cognition and memory assessment

  Change from Baseline to 6 months and 12 months

• Connectivity measures

  Change from Baseline to 6 months

• Connectivity measures

  Change from Baseline to 6 months

Study Arms (2)

Active

EXPERIMENTAL

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

Device: Light Therapy System (LTS): Active Setting

Sham

SHAM COMPARATOR

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

Device: Light Therapy System (LTS): Sham Setting

Interventions

Light Therapy System (LTS): Sham Setting DEVICE

Exposure for 1 hour á day for consecutive days

Sham

Light Therapy System (LTS): Active Setting DEVICE

Exposure for 1 hour á day for consecutive days

Active

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 or in a prodromal stage of AD with at least one positive biomarker of AD.
• Age \> 40 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Copenhagen: collaborator
• Technical University of Denmark: collaborator
• Göteborg University: collaborator
• Zealand University Hospital: lead
• OptoCeutics: collaborator

Study Sites (1)

Zealand University Hospital

Roskilde, 4000, Denmark

RECRUITING

Related Publications (9)

• 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.

  PMID: 22091642 BACKGROUND

• 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.

  PMID: 11355381 BACKGROUND

• 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.

  PMID: 30879788 BACKGROUND

• 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.

  PMID: 27929004 BACKGROUND

• 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.

  PMID: 31836315 BACKGROUND

• 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.

  PMID: 31076275 BACKGROUND

• 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.

  PMID: 34021943 BACKGROUND

• 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.

  PMID: 34661615 BACKGROUND

• 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.

  PMID: 37901795 DERIVED

Related 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)

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Maibritt Horning, MSc

  Zealand University Hospital, Department of Neurology

  STUDY CHAIR

• Mikkel Pejstrup Agger, MD

  Zealand Univeristy Hospital, Department of Neurology

  STUDY CHAIR

• Peter Høgh, MD, Phd

  Zealand Univeristy Hospital, Department of Neurology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peter Høgh, MD, Phd

CONTACT

47322809; phh@regionsjaelland.dk

Maibritt Horning, MSc

CONTACT

+45 81949649; maibho@regionsjaelland.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A parallel-group randomized (1:1), double-blinded, placebo-controlled, clinical trial

Study Record Dates

• First Submitted: January 26, 2022
• First Posted: March 2, 2022
• Study Start: September 20, 2022
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: May 7, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)