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

April 30, 2026 updated by: Zealand University Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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 participation will last 12 months for each participant and consist of 3 periods: An enrollment period, a randomized intervention period of 6 months, and 6 months of active intervention.

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.

Study Type

Interventional

Enrollment (Estimated)

62

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Denmark
      • Roskilde, Denmark, 4000
        • Recruiting
        • Zealand University Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Peter Høgh, MD, Phd
        • Sub-Investigator:
          • Maibritt Horning, MSc
        • Sub-Investigator:
          • Mikkel Pejstrup Agger, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

51 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 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

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active
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
Exposure for 1 hour á day for consecutive days
Sham Comparator: Sham
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
Exposure for 1 hour á day for consecutive days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gamma oscillations assessment
Time Frame: Change from Baseline to 6 months
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
Time Frame: Change from Baseline to 6 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility assessment
Time Frame: Baseline to 6 months

Investigate whether participants can meet the requirements of sitting in front of the LTS device for 1 hour per day. The feasibility of the LTS intervention will be measured by the amount of time (in minutes) of correct device use per day and through a self-report of usage via a compliance/feasibility questionnaire (structured interview on participant's self-reported usage and perception of the LTS device).

Unit: minutes per day of usage
Baseline to 6 months
Compliance assessment
Time Frame: Baseline to 6 months

Investigate the tolerability of the LTS intervention through questionnaires (structured interviews) measured by the number of protocol breaches in total, i.e., not complying with one hour of light stimulation per day during the intervention period, and qualitative assessment based on the compliance/feasibility questionnaire (structured interview on participant's self-reported usage and perception of the LTS device).

Unit: number of total protocol breaches
Baseline to 6 months
Cognition and memory assessment
Time Frame: Change from Baseline to 6 months and 12 months
Assess changes in cognition measured by the Alzheimer's Disease Assessment Scale -Cognitive Subscale plus Executive Functioning and Functional Ability (ADAS Cog plus EF & FA). The score ranges from 0 to 135. A higher score reflects greater cognitive impairment.
Change from Baseline to 6 months and 12 months
Cognition and memory assessment
Time Frame: Change from Baseline to 6 months and 12 months
Assess changes in cognition measured by the Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL). The score ranges from 0 to 78. A higher score reflects a better outcome.
Change from Baseline to 6 months and 12 months
Cognition and memory assessment
Time Frame: Change from Baseline to 6 months and 12 months
Assess changes in cognition measured by the Montreal Cognitive Assessment (MoCA). The score ranges from 0 to 30. A higher score reflects a better outcome.
Change from Baseline to 6 months and 12 months
Connectivity measures
Time Frame: Change from Baseline to 6 months
rs-fMRI Connectivity: Estimate the temporal correlation between cortical regions, assess changes in correlation between cortical regions from baseline to 6 months
Change from Baseline to 6 months
Connectivity measures
Time Frame: Change from Baseline to 6 months
EEG Connectivity: Estimate the temporal correlation between cortical regions, assess changes in correlation between cortical regions from baseline to 6 months
Change from Baseline to 6 months
MR Spectroscopy
Time Frame: Change from Baseline to 6 months
MR Spectroscopy biomarkers: Assess changes from baseline to 6 months
Change from Baseline to 6 months
Sleep Quality
Time Frame: Change from Baseline to 6 months

Assess changes from baseline to 6 months of total sleep time in minutes, measured by actigraphy data and self-reported sleeping patterns (self-reported sleep quality scores based on patient's subjective report alone are often inaccurate).

Unit: total sleep time in minutes
Change from Baseline to 6 months
Sleep Quality
Time Frame: Change from Baseline to 6 months

Assess changes from baseline to 6 months of wakefulness after sleep onset, measured in minutes of wakefulness after a patient has fallen asleep based on actigraphy data.

Unit: total time of wakefulness in minutes
Change from Baseline to 6 months
Biomarkers of Alzheimer's Disease
Time Frame: Change from Baseline to 6 months
Assess changes in biomarkers of Alzheimer's Disease in blood sampled from the participants from baseline to 6 months. Markers of AD will be measured via ultrasensitive assays using fluid-based biomarkers such as plasma levels associated with amyloid pathology (plasma Aβ42/40 ratio), tau (plasma P-tau181 and P-tau231), neurodegeneration (plasma neurofilament light), and astrocytic function (glial fibrillary acidic protein).
Change from Baseline to 6 months
Safety Assessment
Time Frame: 12 months
Estimate the safety of the LTS therapy, assess device- and procedure-related adverse events (DR/PR-AEs) including serious AEs (SAEs) occuring at any time during the trial
12 months
MRI Atrophy assessment
Time Frame: Change from Baseline to 6 months
Assess changes from baseline to 6 months of global atrophy (ventricular volume and hippocampal volume) using advanced MR techniques on structural MRI data, i.e., including but not limited to voxel-based analysis.
Change from Baseline to 6 months
MRI perfusion assessment
Time Frame: Change from Baseline to 6 months
Assess MRI perfusion: Changes from baseline to 6 months.
Change from Baseline to 6 months
EEG: Spectral feature assessment
Time Frame: Change from Baseline to 6 months
Assess spectral features via rs-EEG Fourier power.
Change from Baseline to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Zealand University Hospital

Collaborators

Göteborg University
University of Copenhagen
Technical University of Denmark
OptoCeutics

Investigators

  • Study Chair: Maibritt Horning, MSc, Zealand University Hospital, Department of Neurology
  • Study Chair: Mikkel Pejstrup Agger, MD, Zealand Univeristy Hospital, Department of Neurology
  • Principal Investigator: Peter Høgh, MD, Phd, Zealand Univeristy Hospital, Department of Neurology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 20, 2022

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

January 26, 2022

First Submitted That Met QC Criteria

February 18, 2022

First Posted (Actual)

March 2, 2022

Study Record Updates

Last Update Posted (Actual)

May 7, 2026

Last Update Submitted That Met QC Criteria

April 30, 2026

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ASIII

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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