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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
62
Exposure for 1 hour á day for consecutive days
Exposure for 1 hour á day for consecutive days
Zealand University Hospital
Roskilde, Denmark
RECRUITINGGamma 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.
Time frame: Change from Baseline to 6 months and 7.5 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
Time frame: Change from Baseline to 6 months and 7.5 months
Cognition and memory assessment
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.
Time frame: Change from Baseline to 6 months and 7.5 months
Cognition and memory assessment
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.
Time frame: Change from Baseline to 6 months and 7.5 months
Cognition and memory assessment
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.
Time frame: Change from Baseline to 6 months and 7.5 months
Connectivity measures
rs-fMRI Connectivity: Estimate the temporal correlation between cortical regions, assess changes in correlation between cortical regions from baseline to 6 months and 7.5 months
Time frame: Change from Baseline to 6 months and 7.5 months
Connectivity measures
EEG Connectivity: Estimate the temporal correlation between cortical regions, assess changes in correlation between cortical regions from baseline to 6 months and 7.5 months
Time frame: Change from Baseline to 6 months and 7.5 months
MR Spectroscopy
MR Spectroscopy biomarkers: Assess changes from baseline to 6 months and 7.5 months
Time frame: Change from Baseline to 6 months and 7.5 months
Sleep Quality
Assess changes from baseline to 6 months and 7.5 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
Time frame: Change from Baseline to 6 months and 7.5 months
Sleep Quality
Assess changes from baseline to 6 months and 7.5 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
Time frame: Change from Baseline to 6 months and 7.5 months
Biomarkers of Alzheimer's Disease
Assess changes in biomarkers of Alzheimer's Disease in blood sampled from the participants from baseline to 6 months and 7.5 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).
Time frame: Change from Baseline to 6 months and 7.5 months
Safety Assessment
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
Time frame: 9 months
Feasibility assessment
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
Time frame: Baseline to 6 months
Compliance assessment
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
Time frame: Baseline to 6 months
MRI Atrophy assessment
Assess changes from baseline to 6 months and 7.5 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.
Time frame: Change from Baseline to 6 months and 7.5 months
MRI perfusion assessment
Assess MRI perfusion: Changes from baseline to 6 months and 7.5 months.
Time frame: Change from Baseline to 6 months and 7.5 months
EEG: Spectral feature assessment
Assess spectral features via rs-EEG Fourier power.
Time frame: Change from Baseline to 6 months and 7.5 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.