Alzheimer DiseaseALZLIGHT PilotNCT04574921
Study on Safety, Feasibility and Neural Activation of Non-Invasive Light Therapy System
A study testing Light Therapy System (LTS): Active setting in people with Alzheimer Disease, run by Zealand University Hospital at 1 site in Denmark.
Trial summary
Induction of neural oscillations by flickering light is a well established method used for diagnostic of various neural diseases. Recent studies in mice have shown promising results indicating that induction of gamma oscillation at 40 Hz leads to a reduction in amyloid-β and tau in mice models of Alzheimer's disease. Read more about this study
- Who is it for?
- Ages 55 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Light Therapy System (LTS): Active setting
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Oct 2020to 12 Jul 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adult competent persons able to understand the nature of the study and give written informed consent.
- Stage I: Healthy elderly subject.
- Stage II: Diagnosed with probable mild to moderate AD based on NIA-AA diagnostic criteria.
- Age >55 years and <80 years. Females must be post-menopausal.
- Fluent in Danish
- > 8 year of normal school education
Show all 9Show fewer
- Pass a colour-blindness test (Ishihara colour test)
- Have visual and auditory capabilities, and language skills necessary for neuropsychological testing.
- Furthermore, subjects must have a person, hereafter named designated caregiver, who is available to the participant and can provide the necessary assistance with using the LTS device and Actigraph wearable at home and can assist with clinic visits and other practical issues.
Who cannot join
- Profound visual impairment provided correction with spectacles, if needed.
- Significant abnormalities related to important parts of the brain e.g. the visual system, pre-frontal cortex or hippocampus, or relevant lesions detected by MRI.
- Prior history of significant diseases related to the visual system or the brain.
- Medication Any patient using 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: ALZLIGHT Pilot: Study on Safety, Feasibility and Neural Activation of Non-Invasive Light Therapy System
Induction of neural oscillations by flickering light is a well established method used for diagnostic of various neural diseases.
Recent studies in mice have shown promising results indicating that induction of gamma oscillation at 40 Hz leads to a reduction in amyloid-β and tau in mice models of Alzheimer's disease. This study will use flickering light to induce 40 Hz gamma oscillation as the previously mentioned studies.
Read more
In the study subject will be exposed to invisible spectral flickering light (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 appears as white light.
As this is the first trial, the focus will be on 1) safety of the intervention 2) feasibility of the proposed intervention time and method 3) indication of efficacy.
In stage 1 of the trial 4 age-matched subjects with no Alzheimer's disease will be recruited and be exposed for 1 week. In stage 2 10 patients with Alzheimer's disease will be recruited and exposed for 6 consecutive weeks.
Read the detailed description
Induction of neural oscillations by flickering light is a well established method used for diagnostic of various neural diseases (5,6).
Recent studies in mice have shown promising results indicating that induction of gamma oscillation at 40 Hz leads to a reduction in amyloid-β an tau in mice models of Alzheimer's disease (1-4). This study will use flickering light to induce 40 Hz gamma oscillation as the previously mentioned studies.
This study will utilize a novel way of masking the 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 subject will be exposed to invisible spectral flickering light (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 appears as white light.
As this is the first trial, the focus will be on 1) safety of the intervention 2) feasibility of the proposed intervention time and method 3) indication of efficacy.
In stage 1 of the trial 4 age-matched subjects with no Alzheimer's disease will be recruited and be exposed for 1 week. In stage 2 10 patients with Alzheimer's disease will be recruited and exposed for 6 consecutive weeks. Following the 6 weeks of intervention the subject will have 6 weeks of no intevention and assesed agian.
- Conditions
- Alzheimer Disease
- Being tested
- Light Therapy System (LTS): Active setting, Light Therapy System (LTS): Sham setting
- Keywords
- Gamma entrainment, 40 Hz, Invisible Spectral Flicker, LED, Light Therapy, Brain stimulation, Gamma oscillations, Gamma induction
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Light Therapy System (LTS): Active settingOther
Exposure for 1 hour á day for consecutive days.
Light Therapy System (LTS): Sham settingOther
Exposure for 1 hour á day for consecutive days.
| Study group | Role | What they receive |
|---|---|---|
| Active | Experimental | Exposure to LTS device set to 40 Hz invisible spectral flicker for 1 hour a day for consecutive days Receives: Other: Light Therapy System (LTS): Active setting |
| Sham | Sham comparator | Exposure to LTS device set to continues color matched white light for 1 hour a day for consecutive days Receives: Other: Light Therapy System (LTS): Sham setting |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stage I: Feasibility / Compliance assesment
- The compliance of the LTS intervention will be measured by the amount of time (in minutes) of device use per day.
Measured: After 1 week of intervention
Stage I: Usability Assessment:
- Usability report on use of device during intervention in the subject's home based on device speciffic questionnaire / structured interviews
Measured: After 1 week of intervention
Stage I: Safety Assessment. Evaluation of Adverse Events related to the LTS intervention.
- Safety assessment will be done by collection of all types of adverse events and categorization into severity and relationship to LTS treatment.
Measured: After 1 week of intervention
Stage II: Feasibility / Compliance assesment
- The compliance of the LTS intervention will be measured by the amount of time (in minutes) of device use per day.
Measured: After 6 weeks of intervention and subsequent 6 weeks of no intervention
Stage II: Safety Assessment. Evaluation of Adverse Events related to the LTS intervention.
- Device- and procedure-related adverse events (DR/PR-AEs) including serious AEs (SAEs) occurring at any time during the trial
Measured: After 6 weeks of intervention and subsequent 6 weeks of no intervention
Secondary outcomes (3)
Stage II: Induction of gamma ocsillations
- The effect of the LTS intervention will be measured by the amount of 40 Hz SSVEP response during treatment
Measured: Changes from baseline to 6 and 12 weeks
Stage II: Connectivity meassures in resting-state functional MRI
- rs-fMRI Connectivity: Change from baseline in correlations between cortical regions at 6 weeks
Measured: Changes from baseline to 6 and 12 weeks
Stage II: Connectivity meassures in EEG
- EEG Connectivity: Change from baseline in correlations between cortical regions at 6 weeks
Measured: Changes from baseline to 6 and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2020
- Study start1 Oct 2020
- Primary completion12 Jul 2022
- Study completion12 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Zealand University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zealand University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Technical University of Denmark, University of Copenhagen, OptoCeutics
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04574921
- Sponsor's protocol ID
- REG-085-2020
- Acronym
- ALZLIGHT Pilot
- Status last verified
- Dec 2022
- First submitted
- 27 Aug 2020
- Last updated
- 13 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31076275Adaikkan 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.
PubMed 31836315Iaccarino 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.
PubMed 27929004Martorell 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.
PubMed 30879788Herrmann 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.
PubMed 11355381Kasteleijn-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.
PubMed 22091642
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ALZLIGHT Pilot: Study on Safety, Feasibility and Neural Activation of Non-Invasive Light Therapy System
- ClinicalTrials.gov ID
- NCT04574921
- Acronym / sponsor ID
- ALZLIGHT Pilot / REG-085-2020
- Conditions
- Alzheimer Disease
- Keywords
- Gamma entrainment, 40 Hz, Invisible Spectral Flicker, LED, Light Therapy, Brain stimulation, Gamma oscillations, Gamma induction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Zealand University HospitalUniversity, hospital or other
- Collaborators
- Technical University of Denmark, University of Copenhagen, OptoCeutics
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 12 Jul 2022 (actual)
- Study completion
- 12 Jul 2022 (actual)
- First posted
- 5 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Induction of neural oscillations by flickering light is a well established method used for diagnostic of various neural diseases.
Recent studies in mice have shown promising results indicating that induction of gamma oscillation at 40 Hz leads to a reduction in amyloid-β and tau in mice models of Alzheimer's disease. This study will use flickering light to induce 40 Hz gamma oscillation as the previously mentioned studies.
In the study subject will be exposed to invisible spectral flickering light (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 appears as white light.
As this is the first trial, the focus will be on 1) safety of the intervention 2) feasibility of the proposed intervention time and method 3) indication of efficacy.
In stage 1 of the trial 4 age-matched subjects with no Alzheimer's disease will be recruited and be exposed for 1 week. In stage 2 10 patients with Alzheimer's disease will be recruited and exposed for 6 consecutive weeks.
Detailed description
Induction of neural oscillations by flickering light is a well established method used for diagnostic of various neural diseases (5,6).
Recent studies in mice have shown promising results indicating that induction of gamma oscillation at 40 Hz leads to a reduction in amyloid-β an tau in mice models of Alzheimer's disease (1-4). This study will use flickering light to induce 40 Hz gamma oscillation as the previously mentioned studies.
This study will utilize a novel way of masking the 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 subject will be exposed to invisible spectral flickering light (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 appears as white light.
As this is the first trial, the focus will be on 1) safety of the intervention 2) feasibility of the proposed intervention time and method 3) indication of efficacy.
In stage 1 of the trial 4 age-matched subjects with no Alzheimer's disease will be recruited and be exposed for 1 week. In stage 2 10 patients with Alzheimer's disease will be recruited and exposed for 6 consecutive weeks. Following the 6 weeks of intervention the subject will have 6 weeks of no intevention and assesed agian.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active | Experimental | Other: Light Therapy System (LTS): Active settingExposure to LTS device set to 40 Hz invisible spectral flicker for 1 hour a day for consecutive days |
| Sham | Sham comparator | Other: Light Therapy System (LTS): Sham settingExposure to LTS device set to continues color matched white light for 1 hour a day for consecutive days |
Who may qualify
- Ages
- 55 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Adult competent persons able to understand the nature of the study and give written informed consent.
- Stage I: Healthy elderly subject.
- Stage II: Diagnosed with probable mild to moderate AD based on NIA-AA diagnostic criteria.
- Age >55 years and <80 years. Females must be post-menopausal.
- Fluent in Danish
Key exclusion criteria (6 listed)
- Profound visual impairment provided correction with spectacles, if needed.
- Significant abnormalities related to important parts of the brain e.g. the visual system, pre-frontal cortex or hippocampus, or relevant lesions detected by MRI.
- Prior history of significant diseases related to the visual system or the brain.
- Medication Any patient using antiepileptic drugs, neuromodulating drugs or high dose of sedatives will be excluded.
- Prior history of substance abuse within the past 2 years.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Light Therapy System (LTS): Active settingExposure for 1 hour á day for consecutive days. | Other | Active |
| Light Therapy System (LTS): Sham settingExposure for 1 hour á day for consecutive days. | Other | Sham |
Primary outcome
Stage I: Feasibility / Compliance assesment
Time frame: After 1 week of intervention
• The compliance of the LTS intervention will be measured by the amount of time (in minutes) of device use per day.
Stage I: Usability Assessment:
Time frame: After 1 week of intervention
• Usability report on use of device during intervention in the subject's home based on device speciffic questionnaire / structured interviews
Stage I: Safety Assessment. Evaluation of Adverse Events related to the LTS intervention.
Time frame: After 1 week of intervention
• Safety assessment will be done by collection of all types of adverse events and categorization into severity and relationship to LTS treatment.
Stage II: Feasibility / Compliance assesment
Time frame: After 6 weeks of intervention and subsequent 6 weeks of no intervention
• The compliance of the LTS intervention will be measured by the amount of time (in minutes) of device use per day.
Stage II: Safety Assessment. Evaluation of Adverse Events related to the LTS intervention.
Time frame: After 6 weeks of intervention and subsequent 6 weeks of no intervention
• Device- and procedure-related adverse events (DR/PR-AEs) including serious AEs (SAEs) occurring at any time during the trial
3 secondary outcomes
Stage II: Induction of gamma ocsillations
Time frame: Changes from baseline to 6 and 12 weeks
Stage II: Connectivity meassures in resting-state functional MRI
Time frame: Changes from baseline to 6 and 12 weeks
Stage II: Connectivity meassures in EEG
Time frame: Changes from baseline to 6 and 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2022.
- Background: PubMed 31076275Adaikkan 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.
- Background: PubMed 31836315Adaikkan 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.
- Background: PubMed 27929004Iaccarino 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.
- Background: PubMed 30879788Martorell 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.
- Background: PubMed 11355381Herrmann 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.
- Background: PubMed 22091642Kasteleijn-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.
- Carstensen M et al. 40 Hz invisible spectral flicker and its potential use in Alzheimer's light therapy treatment. Proc. SPIE 11221, Mechanisms of Photobiomodulation Therapy XV, 112210L (11 March 2020)Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Light Therapy System (LTS): Active setting in people with Alzheimer Disease, run by Zealand University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stage I: Feasibility / Compliance assesment (time frame: After 1 week of intervention). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04574921, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2022.