Alzheimer's Disease
Conditions
Keywords
Gamma Entrainment, 40 Hz, Invisible Spectral Flicker, LED, Light Therapy, Brain Stimulation, Gamma Oscillations, Gamma Induction
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 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.
Interventions
Exposure for 1 hour á day for consecutive days
Exposure for 1 hour á day for consecutive days
Sponsors
Zealand University Hospital
OptoCeutics
University of Copenhagen
Technical University of Denmark
Göteborg University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Double-blinded
Intervention model description
A parallel-group randomized (1:1), double-blinded, placebo-controlled, clinical trial
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gamma oscillations assessment | 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. |
| Induction of 40 Hz Gamma oscillations | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Connectivity measures | 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 |
| MR Spectroscopy | Change from Baseline to 6 months | MR Spectroscopy biomarkers: Assess changes from baseline to 6 months |
| Sleep Quality | 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 |
| Biomarkers of Alzheimer's Disease | 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). |
| Safety Assessment | 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 |
| Feasibility assessment | 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 |
| Compliance assessment | 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 |
| MRI Atrophy assessment | 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. |
| EEG: Spectral feature assessment | Change from Baseline to 6 months | Assess spectral features via rs-EEG Fourier power. |
| MRI perfusion assessment | Change from Baseline to 6 months | Assess MRI perfusion: Changes from baseline to 6 months. |
| Cognition and memory assessment | 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. |
Countries
Denmark
Contacts
CONTACTPeter Høgh, MD, Phd
CONTACTMaibritt Horning, MSc
STUDY_CHAIRMaibritt Horning, MSc
Zealand University Hospital, Department of Neurology
STUDY_CHAIRMikkel Pejstrup Agger, MD
Zealand Univeristy Hospital, Department of Neurology
PRINCIPAL_INVESTIGATORPeter Høgh, MD, Phd
Zealand Univeristy Hospital, Department of Neurology
Outcome results
None listed