Clinical trial NCT05260177: Study on the Effect of 40 Hz Non-Invasive Light Therapy System
Official title: ALZLIGHT Stage III - Study on the Effect of 40 Hz Non-Invasive Light Therapy System
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alzheimer's Disease
Keywords: Gamma Entrainment
40 Hz
Invisible Spectral Flicker
LED
Light Therapy
Brain Stimulation
Gamma Oscillations
Gamma Induction
Lead sponsor: Zealand University Hospital
Sponsor class: OTHER
Collaborators: name: OptoCeutics
name: University of Copenhagen
name: Technical University of Denmark
name: Göteborg University
First posted: 2022-03-02
Enrollment: 62
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A parallel-group randomized (1:1), double-blinded, placebo-controlled, clinical trial
Primary purpose: TREATMENT

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.

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 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Gamma oscillations assessment
timeFrame: Change from Baseline to 6 months and 7.5 months
measure: Induction of 40 Hz Gamma oscillations
timeFrame: Change from Baseline to 6 months and 7.5 months
Secondary outcomes:
measure: Cognition and memory assessment
timeFrame: Change from Baseline to 6 months and 7.5 months
measure: Cognition and memory assessment
timeFrame: Change from Baseline to 6 months and 7.5 months
measure: Cognition and memory assessment
timeFrame: Change from Baseline to 6 months and 7.5 months
measure: Connectivity measures
timeFrame: Change from Baseline to 6 months and 7.5 months
measure: Connectivity measures
timeFrame: Change from Baseline to 6 months and 7.5 months
measure: MR Spectroscopy
timeFrame: Change from Baseline to 6 months and 7.5 months
measure: Sleep Quality
timeFrame: Change from Baseline to 6 months and 7.5 months
measure: Sleep Quality
timeFrame: Change from Baseline to 6 months and 7.5 months
measure: Biomarkers of Alzheimer's Disease
timeFrame: Change from Baseline to 6 months and 7.5 months
measure: Safety Assessment
timeFrame: 9 months
measure: Feasibility assessment
timeFrame: Baseline to 6 months
measure: Compliance assessment
timeFrame: Baseline to 6 months
measure: MRI Atrophy assessment
timeFrame: Change from Baseline to 6 months and 7.5 months
measure: MRI perfusion assessment
timeFrame: Change from Baseline to 6 months and 7.5 months
measure: EEG: Spectral feature assessment
timeFrame: Change from Baseline to 6 months and 7.5 months
Other outcomes:
Locations:
city: Roskilde
country: Denmark
facility: Zealand University Hospital
Study officials:
affiliation: Zealand University Hospital, Department of Neurology
name: Maibritt Horning, MSc
role: STUDY_CHAIR
affiliation: Zealand Univeristy Hospital, Department of Neurology
name: Mikkel Pejstrup Agger, MD
role: STUDY_CHAIR
affiliation: Zealand Univeristy Hospital, Department of Neurology
name: Peter Høgh, MD, Phd
role: PRINCIPAL_INVESTIGATOR
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