Alzheimer's Disease Clinical Trial
Official title:
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.
Status | Recruiting |
Enrollment | 62 |
Est. completion date | December 1, 2026 |
Est. primary completion date | May 30, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 55 Years and older |
Eligibility | 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) |
Country | Name | City | State |
---|---|---|---|
Denmark | Zealand University Hospital | Roskilde |
Lead Sponsor | Collaborator |
---|---|
Zealand University Hospital | Göteborg University, OptoCeutics, Technical University of Denmark, University of Copenhagen |
Denmark,
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. Erratum In: Nature. 2018 Oct;562(7725):E1. — View Citation
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. — View Citation
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 and 7.5 months | |
Primary | 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 and 7.5 months | |
Secondary | 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. | Change from Baseline to 6 months and 7.5 months | |
Secondary | 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. | Change from Baseline to 6 months and 7.5 months | |
Secondary | 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. | Change from Baseline to 6 months and 7.5 months | |
Secondary | 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 | Change from Baseline to 6 months and 7.5 months | |
Secondary | 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 | Change from Baseline to 6 months and 7.5 months | |
Secondary | MR Spectroscopy | MR Spectroscopy biomarkers: Assess changes from baseline to 6 months and 7.5 months | Change from Baseline to 6 months and 7.5 months | |
Secondary | 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 |
Change from Baseline to 6 months and 7.5 months | |
Secondary | 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 |
Change from Baseline to 6 months and 7.5 months | |
Secondary | 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 Aß42/40 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 and 7.5 months | |
Secondary | 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 | 9 months | |
Secondary | 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 |
Baseline to 6 months | |
Secondary | 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 |
Baseline to 6 months | |
Secondary | 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. | Change from Baseline to 6 months and 7.5 months | |
Secondary | MRI perfusion assessment | Assess MRI perfusion: Changes from baseline to 6 months and 7.5 months. | Change from Baseline to 6 months and 7.5 months | |
Secondary | EEG: Spectral feature assessment | Assess spectral features via rs-EEG Fourier power. | Change from Baseline to 6 months and 7.5 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT05040048 -
Taxonomy of Neurodegenerative Diseases : Observational Study in Alzheimer's Disease and Parkinson's Disease
|
||
Withdrawn |
NCT03316898 -
A FDG-PET Study of AGN-242071 Added to Standard-of-Care (Donepezil ± Memantine) for the Treatment of Participants With Mild to Moderate Alzheimer's Disease
|
Phase 1 | |
Withdrawn |
NCT02860065 -
CPC-201 Alzheimer's Disease Type Dementia: PET Study
|
Phase 2 | |
Completed |
NCT01315639 -
New Biomarker for Alzheimer's Disease Diagnostic
|
N/A | |
Not yet recruiting |
NCT03740178 -
Multiple Dose Trial of MK-4334 in Participants With Alzheimer's Clinical Syndrome (MK-4334-005)
|
Phase 1 | |
Recruiting |
NCT05607615 -
A 6-Month Study to Evaluate the Safety & Potential Efficacy of Trappsol Cyclo in Patients With Early Alzheimer's Disease
|
Phase 2 | |
Terminated |
NCT03307993 -
Positron Emission Tomography (PET) Study in Patients With Alzheimer's Disease
|
Phase 1 | |
Recruiting |
NCT02912936 -
A Medium Chain Triglyceride Intervention for Patients With Alzheimer Disease
|
N/A | |
Active, not recruiting |
NCT02899091 -
Evaluation of the Safety and Potential Therapeutic Effects of CB-AC-02 in Patients With Alzheimer's Disease
|
Phase 1/Phase 2 | |
Completed |
NCT02907567 -
Clinical Trial of CT1812 in Mild to Moderate Alzheimer's Disease
|
Phase 1/Phase 2 | |
Not yet recruiting |
NCT02868905 -
Identification of Epigenetic Markers Common to Obesity and Alzheimer's Disease in Women
|
N/A | |
Completed |
NCT02580305 -
SUVN-502 With Donepezil and Memantine for the Treatment of Moderate Alzheimer's Disease- Phase 2a Study
|
Phase 2 | |
Completed |
NCT02516046 -
18F-AV-1451 Autopsy Study
|
Phase 3 | |
Terminated |
NCT02521558 -
Effectiveness of Home-based Electronic Cognitive Therapy in Alzheimer's Disease
|
N/A | |
Recruiting |
NCT02247180 -
Cognitive Rehabilitation in Alzheimer`s Disease
|
N/A | |
Terminated |
NCT02220738 -
Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ABT-957 in Subjects With Mild-to-Moderate Alzheimer's Disease on Stable Doses of Acetylcholinesterase Inhibitors
|
Phase 1 | |
Completed |
NCT02260167 -
Treatment of Alzheimer's and Dementia With the Metabolism, Infections, Nutrition, Drug Elimination (MIND) Protocol
|
N/A | |
Completed |
NCT02317523 -
Alzheimer's Caregiver Coping: Mental and Physical Health
|
N/A | |
Completed |
NCT02256306 -
The PLasma for Alzheimer SymptoM Amelioration (PLASMA) Study
|
N/A | |
Completed |
NCT02089555 -
African American Alzheimer's Progression Markers - CSF and Neuro-Imaging
|
N/A |