Study on Safety, Feasibility and Neural Activation of Non-Invasive Light Therapy System

NCT04574921 | Completed DMC

• 1 other identifier: REG-085-2020
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Alzheimer Disease

Keywords

Gamma entrainment; 40 Hz; Invisible Spectral Flicker; LED; Light Therapy; Brain stimulation; Gamma oscillations; Gamma induction

Outcome Measures

Primary Outcomes (5)

• 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.

  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

  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.

  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.

  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

  After 6 weeks of intervention and subsequent 6 weeks of no intervention

Secondary Outcomes (3)

• Stage II: Induction of gamma ocsillations

  Changes from baseline to 6 and 12 weeks

• Stage II: Connectivity meassures in resting-state functional MRI

  Changes from baseline to 6 and 12 weeks

• Stage II: Connectivity meassures in EEG

  Changes from baseline to 6 and 12 weeks

Other Outcomes (7)

• Stage II: Changes in cognition:

  Changes from baseline to 6 and 12 weeks

• Stage II: Changes in cognition:

  Changes from baseline to 6 and 12 weeks

• Stage II: Changes MR spectroscopy

  Changes from baseline to 6 and 12 weeks

Study Arms (2)

Active

EXPERIMENTAL

Exposure to LTS device set to 40 Hz invisible spectral flicker for 1 hour a day for consecutive days

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

Other: Light Therapy System (LTS): Sham setting

Interventions

Light Therapy System (LTS): Active setting OTHER

Exposure for 1 hour á day for consecutive days.

Active

Light Therapy System (LTS): Sham setting OTHER

Exposure for 1 hour á day for consecutive days.

Sham

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zealand University Hospital: lead
• Technical University of Denmark: collaborator
• University of Copenhagen: collaborator
• OptoCeutics: collaborator

Study Sites (1)

Zealand University DK34197393

Roskilde, Region Sjælland, 4000, Denmark

Location

Related Publications (6)

• 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.

  PMID: 31076275 BACKGROUND

• 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.

  PMID: 31836315 BACKGROUND

• 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.

  PMID: 27929004 BACKGROUND

• 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.

  PMID: 30879788 BACKGROUND

• 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.

  PMID: 11355381 BACKGROUND

• 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.

  PMID: 22091642 BACKGROUND

Related Links

• 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)

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2020
• First Posted: October 5, 2020
• Study Start: October 1, 2020
• Primary Completion: July 12, 2022
• Study Completion: July 12, 2022
• Last Updated: December 13, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)