Trial Outcomes & Findings for Impact of Photobiomodulation (PBM) on Biomarkers of Alzheimer's Disease (NCT NCT03405662)

NCT ID: NCT03405662

Last Updated: 2022-07-01

Results Overview

The ADAS-cog is the most popular cognitive testing instrument used in clinical trials of nootropics. It consists of 11 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities which are often referred to as the core symptoms of AD. Higher ADAS-cog scores indicate greater cognitive impairment. The changes score was determined by calculating the ratio of the ADAS-cog score at week 16 over the ADAS-cog score at baseline. Thus, a change score of 1 signifies no change compared to baseline and change scores \< 1 or \> 1 reflect a decrease or an increase in ADAS-cog score compared to baseline.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 23 participants
• Primary outcome timeframe: Baseline to 16 weeks
• Results posted on: 2022-07-01

Participant Flow

Twenty-three (23) participants signed informed consent forms/were enrolled in the study. Nine (9) of these participants did not meet study inclusion criteria (e.g., baseline MMSEs were too low, or did not have AD biomarkers). Fourteen (14) participants were randomized: 7 to Active PBM; 7 to Sham PBM.

Participant milestones

Measure	Acitve PBM This arm will receive active photobiomodulation (PBM), delivered with the Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Vielight Neuro Gamma: The Vielight Neuro Gamma is headset that delivers transcranial (through the scalp and skull) and intranasal (through the nose) near infrared (NIR) light. The device is engineered for increased efficacy and easy domestic use for comprehensive brain photobiomodulation (PBM). The NIR lights are pulsed at a 40 Hz rate, which correlates with electroencephalogram (EEG) gamma brain wave entrainment.	Sham PBM This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.
Overall Study STARTED	7	7
Overall Study COMPLETED	6	4
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Measure	Acitve PBM This arm will receive active photobiomodulation (PBM), delivered with the Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Vielight Neuro Gamma: The Vielight Neuro Gamma is headset that delivers transcranial (through the scalp and skull) and intranasal (through the nose) near infrared (NIR) light. The device is engineered for increased efficacy and easy domestic use for comprehensive brain photobiomodulation (PBM). The NIR lights are pulsed at a 40 Hz rate, which correlates with electroencephalogram (EEG) gamma brain wave entrainment.	Sham PBM This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.
Overall Study COVID-19 restriction	1	0
Overall Study unblinding	0	1
Overall Study placement in memory care facility	0	2

Baseline Characteristics

Impact of Photobiomodulation (PBM) on Biomarkers of Alzheimer's Disease

Baseline characteristics by cohort

Measure	Acitve PBM n=7 Participants This arm will receive active photobiomodulation (PBM), delivered with the Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Vielight Neuro Gamma: The Vielight Neuro Gamma is headset that delivers transcranial (through the scalp and skull) and intranasal (through the nose) near infrared (NIR) light. The device is engineered for increased efficacy and easy domestic use for comprehensive brain photobiomodulation (PBM). The NIR lights are pulsed at a 40 Hz rate, which correlates with electroencephalogram (EEG) gamma brain wave entrainment.	Sham PBM n=7 Participants This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.	Total n=14 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Age, Continuous	68.1 years n=5 Participants	72.4 years n=7 Participants	70.3 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Mini-Mental State Exam (MMSE)	23.4 units on a scale STANDARD_DEVIATION 7.1 • n=5 Participants	21.6 units on a scale STANDARD_DEVIATION 4.4 • n=7 Participants	22.5 units on a scale STANDARD_DEVIATION 5.7 • n=5 Participants
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)	35.5 units on a scale STANDARD_DEVIATION 8.3 • n=5 Participants	27.5 units on a scale STANDARD_DEVIATION 20.0 • n=7 Participants	31.5 units on a scale STANDARD_DEVIATION 15.3 • n=5 Participants
Neuropsychiatric Inventory (NPI)	42.0 units on a scale STANDARD_DEVIATION 29.8 • n=5 Participants	21 units on a scale STANDARD_DEVIATION 50.7 • n=7 Participants	31.5 units on a scale STANDARD_DEVIATION 41.5 • n=5 Participants
Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale (ADCS-ADL)	57.0 units on a scale STANDARD_DEVIATION 7.5 • n=5 Participants	68.4 units on a scale STANDARD_DEVIATION 8.2 • n=7 Participants	62.7 units on a scale STANDARD_DEVIATION 9.6 • n=5 Participants
Color Trails Test (CTT), 1	114.1 seconds STANDARD_DEVIATION 64.7 • n=5 Participants	69.4 seconds STANDARD_DEVIATION 33.0 • n=7 Participants	95.5 seconds STANDARD_DEVIATION 56.7 • n=5 Participants
CTT2	248.3 seconds STANDARD_DEVIATION 57.6 • n=5 Participants	147.8 seconds STANDARD_DEVIATION 75.4 • n=7 Participants	206.4 seconds STANDARD_DEVIATION 80.9 • n=5 Participants
CTT2/CTT1, index	2.0 ratio STANDARD_DEVIATION 1.2 • n=5 Participants	1.2 ratio STANDARD_DEVIATION 0.9 • n=7 Participants	1.6 ratio STANDARD_DEVIATION 1.1 • n=5 Participants
Plasma Aβ40	223.2 pg/mL STANDARD_DEVIATION 74 • n=5 Participants	219.0 pg/mL STANDARD_DEVIATION 9 • n=7 Participants	220.3 pg/mL STANDARD_DEVIATION 55 • n=5 Participants
Plasma Aβ42	21.3 pg/mL STANDARD_DEVIATION 6 • n=5 Participants	20.0 pg/mL STANDARD_DEVIATION 3 • n=7 Participants	20.7 pg/mL STANDARD_DEVIATION 5 • n=5 Participants
Plasma Aβ 42/40	0.08 ratio STANDARD_DEVIATION 0.01 • n=5 Participants	0.08 ratio STANDARD_DEVIATION 0.01 • n=7 Participants	0.08 ratio STANDARD_DEVIATION 0.01 • n=5 Participants
Plasma tau	1.6 pg/mL STANDARD_DEVIATION 0.3 • n=5 Participants	1.4 pg/mL STANDARD_DEVIATION 0.3 • n=7 Participants	1.5 pg/mL STANDARD_DEVIATION 0.4 • n=5 Participants
Plasma P-tau181	5.9 pg/mL STANDARD_DEVIATION 1.5 • n=5 Participants	5.2 pg/mL STANDARD_DEVIATION 1.7 • n=7 Participants	5.7 pg/mL STANDARD_DEVIATION 1.6 • n=5 Participants
Plasma neurofilament light chain (NfL)	14.3 pg/mL STANDARD_DEVIATION 5 • n=5 Participants	17.2 pg/mL STANDARD_DEVIATION 4 • n=7 Participants	15.8 pg/mL STANDARD_DEVIATION 5 • n=5 Participants
Plasma glial fibrillary acidic protein (GFAP)	262.5 pg/mL STANDARD_DEVIATION 79 • n=5 Participants	276.4 pg/mL STANDARD_DEVIATION 96 • n=7 Participants	269.5 pg/mL STANDARD_DEVIATION 88 • n=5 Participants
cerebrospinal fluid (CSF) Aβ40	26.7 pg/mL x 10^3 STANDARD_DEVIATION 9 • n=5 Participants	20.4 pg/mL x 10^3 STANDARD_DEVIATION 7 • n=7 Participants	23.6 pg/mL x 10^3 STANDARD_DEVIATION 8 • n=5 Participants
CSF Aβ42	3.4 pg/mL x 10^3 STANDARD_DEVIATION 2 • n=5 Participants	1.9 pg/mL x 10^3 STANDARD_DEVIATION 0.6 • n=7 Participants	2.7 pg/mL x 10^3 STANDARD_DEVIATION 1.4 • n=5 Participants
CSF Aβ42/40	0.1 ratio STANDARD_DEVIATION 0.1 • n=5 Participants	0.1 ratio STANDARD_DEVIATION 0.02 • n=7 Participants	0.1 ratio STANDARD_DEVIATION 0.07 • n=5 Participants
CSF tau	505 pg/mL STANDARD_DEVIATION 323 • n=5 Participants	382 pg/mL STANDARD_DEVIATION 322 • n=7 Participants	444 pg/mL STANDARD_DEVIATION 319 • n=5 Participants
CSF P-tau181	439 pg/mL STANDARD_DEVIATION 194 • n=5 Participants	335 pg/mL STANDARD_DEVIATION 202 • n=7 Participants	388 pg/mL STANDARD_DEVIATION 199 • n=5 Participants
CSF neurofilament light chain (NfL)	3.4 pg/mL x 10^3 STANDARD_DEVIATION 1 • n=5 Participants	3.3 pg/mL x 10^3 STANDARD_DEVIATION 2 • n=7 Participants	3.4 pg/mL x 10^3 STANDARD_DEVIATION 2 • n=5 Participants
CSF glial fibrillary acidic protein (GFAP)	50.1 pg/mL x 10^3 STANDARD_DEVIATION 43 • n=5 Participants	54.2 pg/mL x 10^3 STANDARD_DEVIATION 36 • n=7 Participants	52.2 pg/mL x 10^3 STANDARD_DEVIATION 40 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 16 weeks

Population: One Active PBM patient did not return for post-treatment assessment due to pandemic-related lock-down. Two Sham PBM patients did not return for post-treatment assessment due to worsening of symptoms that necessitated placement in memory care facility. One Sham PBM patient was excluded due to unblinding.

The ADAS-cog is the most popular cognitive testing instrument used in clinical trials of nootropics. It consists of 11 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities which are often referred to as the core symptoms of AD. Higher ADAS-cog scores indicate greater cognitive impairment.

The changes score was determined by calculating the ratio of the ADAS-cog score at week 16 over the ADAS-cog score at baseline. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in ADAS-cog score compared to baseline.

Outcome measures

Measure	Acitve PBM n=6 Participants This arm will receive active photobiomodulation (PBM), delivered with the Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Vielight Neuro Gamma: The Vielight Neuro Gamma is headset that delivers transcranial (through the scalp and skull) and intranasal (through the nose) near infrared (NIR) light. The device is engineered for increased efficacy and easy domestic use for comprehensive brain photobiomodulation (PBM). The NIR lights are pulsed at a 40 Hz rate, which correlates with electroencephalogram (EEG) gamma brain wave entrainment.	Sham PBM n=4 Participants This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.
Change in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog)	0.94 Ratio Standard Deviation 0.2	1.4 Ratio Standard Deviation 0.2

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Population: One Active PBM patient did not return for post-treatment assessment due to pandemic-related lock-down. Two Sham PBM patients did not return for post-treatment assessment due to worsening of symptoms that necessitated placement in memory care facility. One Sham PBM patient was excluded due to unblinding.

CTT is a non-verbal test of visual attention, graphomotor sequencing, and effortful executive processing abilities (i.e., sustained attention and set shifting). A higher index score indicates less cognitive flexibility, a lower ability to shift attention.

Outcome measures

Measure	Acitve PBM n=6 Participants This arm will receive active photobiomodulation (PBM), delivered with the Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Vielight Neuro Gamma: The Vielight Neuro Gamma is headset that delivers transcranial (through the scalp and skull) and intranasal (through the nose) near infrared (NIR) light. The device is engineered for increased efficacy and easy domestic use for comprehensive brain photobiomodulation (PBM). The NIR lights are pulsed at a 40 Hz rate, which correlates with electroencephalogram (EEG) gamma brain wave entrainment.	Sham PBM n=4 Participants This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.
Change in Performance on Color Trails Test (CTT2/CTT1 Index)	1.1 Ratio Standard Deviation 1	1.2 Ratio Standard Deviation 0.08

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Population: One Active PBM patient did not return for post-treatment assessment due to pandemic-related lock-down. Two Sham PBM patients did not return for post-treatment assessment due to worsening of symptoms that necessitated placement in memory care facility. One Sham PBM patient was excluded due to unblinding.

NPI is a well-validated, reliable, multi-item instrument to assess psychopathology (e.g., behavioral symptoms) in AD based on a questionnaire completed by the participants' study partners. Higher scores indicate more symptoms and/or more severe symptoms.

The changes score was determined by calculating the ratio of the week 16 NPI score over the baseline NPI score. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in NPI compared to baseline.

Outcome measures

Measure	Acitve PBM n=6 Participants This arm will receive active photobiomodulation (PBM), delivered with the Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Vielight Neuro Gamma: The Vielight Neuro Gamma is headset that delivers transcranial (through the scalp and skull) and intranasal (through the nose) near infrared (NIR) light. The device is engineered for increased efficacy and easy domestic use for comprehensive brain photobiomodulation (PBM). The NIR lights are pulsed at a 40 Hz rate, which correlates with electroencephalogram (EEG) gamma brain wave entrainment.	Sham PBM n=4 Participants This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.
Change on the Neuropsychiatriac Inventory (NPI)	1.1 Ratio Standard Deviation 2.2	1.87 Ratio Standard Deviation 0.5

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Population: One Active PBM patient did not return for post-treatment assessment due to pandemic-related lock-down. Two Sham PBM patients did not return for post-treatment assessment due to worsening of symptoms that necessitated placement in memory care facility. One Sham PBM patient was excluded due to unblinding.

ADCS-ADL assesses the competence of patients with AD in basic and instrumental activities of daily living (ADLs). It can be completed by a caregiver in questionnaire format, or administered by a clinician/researcher as a structured interview with a caregiver. ADCS-ADL scores range from 0-53, with higher scores indicating greater independence. The changes score was determined by calculating the ratio of the week 16 ADCS-ADL score over the baseline ADCS-ADL score. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in ADCS-ADL compared to baseline.

Outcome measures

Measure	Acitve PBM n=6 Participants This arm will receive active photobiomodulation (PBM), delivered with the Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Vielight Neuro Gamma: The Vielight Neuro Gamma is headset that delivers transcranial (through the scalp and skull) and intranasal (through the nose) near infrared (NIR) light. The device is engineered for increased efficacy and easy domestic use for comprehensive brain photobiomodulation (PBM). The NIR lights are pulsed at a 40 Hz rate, which correlates with electroencephalogram (EEG) gamma brain wave entrainment.	Sham PBM n=4 Participants This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.
Change on the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL)	1.0 Ratio Standard Deviation 2.2	0.9 Ratio Standard Deviation 0.07

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Population: One Active REAL PBM patient did not return for post-treatment assessment due to pandemic-related lock-down; another REAL PBM patient's post-treatment sample was contaminated. One SHAM patient was excluded for unblinding, two SHAM patients were institutionalized during the study; two other SHAM patients had failed lumbar punctures.

Although Aβ42 is present in plasma, it is unclear whether it originates from peripheral sources or from the brain. Because Aβ can be transported bidirectionally across the blood-brain barrier, it has been hypothesized that there may be an equilibrium between CSF and plasma pools of Aβ. Decreased levels of Aβ42 in CSF occurs in conjunction with cognitive decline. However, patients with mutations in chromosome 21 that cause early-onset familial AD and patients with trisomy 21 have increased levels of plasma Aβ42 before the onset of the symptoms of dementia. Therefore, it is possible that plasma Aβ42 levels increase with cognitive decline. The change score was determined by calculating the ratio of plasma Aβ42 at week 16 over the ADAS-cog score at baseline.

Outcome measures

Measure	Acitve PBM n=5 Participants This arm will receive active photobiomodulation (PBM), delivered with the Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Vielight Neuro Gamma: The Vielight Neuro Gamma is headset that delivers transcranial (through the scalp and skull) and intranasal (through the nose) near infrared (NIR) light. The device is engineered for increased efficacy and easy domestic use for comprehensive brain photobiomodulation (PBM). The NIR lights are pulsed at a 40 Hz rate, which correlates with electroencephalogram (EEG) gamma brain wave entrainment.	Sham PBM n=2 Participants This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.
Change in Plasma Levels of Aβ42	0.92 Ratio Standard Deviation 0.1	1.0 Ratio Standard Deviation 0.1

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Population: One Active REAL PBM patient did not return for post-treatment assessment due to pandemic-related lock-down; two REAL PBM patient's post-treatment samples were contaminated. One SHAM patient was excluded for unblinding, two SHAM patients were institutionalized during the study; two other SHAM patients had failed lumbar punctures.

Aβ42 is a biomarker of AD pathology. CSF levels of Aβ42 decrease in conjunction with the cognitive decline. The change score was determined by calculating the ratio of CSF Aβ42 at week 16 over the ADAS-cog score at baseline. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in CSF levels of Aβ42 compared to baseline.

Outcome measures

Measure	Acitve PBM n=4 Participants This arm will receive active photobiomodulation (PBM), delivered with the Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Vielight Neuro Gamma: The Vielight Neuro Gamma is headset that delivers transcranial (through the scalp and skull) and intranasal (through the nose) near infrared (NIR) light. The device is engineered for increased efficacy and easy domestic use for comprehensive brain photobiomodulation (PBM). The NIR lights are pulsed at a 40 Hz rate, which correlates with electroencephalogram (EEG) gamma brain wave entrainment.	Sham PBM n=2 Participants This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.
Change in CSF Levels of Aβ42.	0.4 Ratio Standard Deviation 0.1	1.3 Ratio Standard Deviation 0.3

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Population: One Active REAL PBM patient did not return for post-treatment assessment due to pandemic-related lock-down; another REAL PBM patient's post-treatment sample was contaminated. One SHAM patient was excluded for unblinding, two SHAM patients were institutionalized during the study; two other SHAM patients had failed lumbar punctures.

Tau, the microtubule-associated protein, forms insoluble filaments that accumulate as neurofibrillary tangles in Alzheimer's disease (AD). Research suggests that plasma tau levels increased with AD severity. The change score was determined by calculating the ratio of the week 16 plasma tau over the baseline plasma tau levels. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in plasma tau compared to baseline.

Outcome measures

Measure	Acitve PBM n=5 Participants This arm will receive active photobiomodulation (PBM), delivered with the Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Vielight Neuro Gamma: The Vielight Neuro Gamma is headset that delivers transcranial (through the scalp and skull) and intranasal (through the nose) near infrared (NIR) light. The device is engineered for increased efficacy and easy domestic use for comprehensive brain photobiomodulation (PBM). The NIR lights are pulsed at a 40 Hz rate, which correlates with electroencephalogram (EEG) gamma brain wave entrainment.	Sham PBM n=2 Participants This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.
Change in Plasma Levels of Tau.	0.7 Ratio Standard Deviation 0.2	1.0 Ratio Standard Deviation 0.1

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Population: One Active REAL PBM patient did not return for post-treatment assessment due to pandemic-related lock-down; two REAL PBM patient's post-treatment samples were contaminated. One SHAM patient was excluded for unblinding, two SHAM patients were institutionalized during the study; two other SHAM patients had failed lumbar punctures.

Tau forms insoluble filaments that accumulate as neurofibrillary tangles in AD. Increased levels of tau in CSF is a key characteristic of AD and is considered to result from neurodegeneration. The change score was determined by calculating the ratio of week 16 CSF tau over baseline CSF tau. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in CSF tau compared to baseline.

Outcome measures

Measure	Acitve PBM n=4 Participants This arm will receive active photobiomodulation (PBM), delivered with the Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Vielight Neuro Gamma: The Vielight Neuro Gamma is headset that delivers transcranial (through the scalp and skull) and intranasal (through the nose) near infrared (NIR) light. The device is engineered for increased efficacy and easy domestic use for comprehensive brain photobiomodulation (PBM). The NIR lights are pulsed at a 40 Hz rate, which correlates with electroencephalogram (EEG) gamma brain wave entrainment.	Sham PBM n=2 Participants This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.
Change in CSF Levels of Tau	0.7 Ratio Standard Deviation 0.5	1.1 Ratio Standard Deviation 0.3

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Population: One Active REAL PBM patient did not return for post-treatment assessment due to pandemic-related lock-down; another REAL PBM patient's post-treatment sample was contaminated. One SHAM patient was excluded for unblinding, two SHAM patients were institutionalized during the study; two other SHAM patients had failed lumbar punctures.

Neurofilament light chain (NfL) is a marker of axonal degeneration and is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD. The change score was determined by calculating the ratio of week 16 plasma levels of NfL over the baseline levels of plasma NfL. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in plasma levels of NfL compared to baseline.

Outcome measures

Measure	Acitve PBM n=5 Participants This arm will receive active photobiomodulation (PBM), delivered with the Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Vielight Neuro Gamma: The Vielight Neuro Gamma is headset that delivers transcranial (through the scalp and skull) and intranasal (through the nose) near infrared (NIR) light. The device is engineered for increased efficacy and easy domestic use for comprehensive brain photobiomodulation (PBM). The NIR lights are pulsed at a 40 Hz rate, which correlates with electroencephalogram (EEG) gamma brain wave entrainment.	Sham PBM n=2 Participants This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.
Change in Plasma Levels of Neurofilament Light Chain (NfL)	1.0 Ratio Standard Deviation 0.2	1.2 Ratio Standard Deviation 0.4

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Population: One Active REAL PBM patient did not return for post-treatment assessment due to pandemic-related lock-down; two REAL PBM patient's post-treatment samples were contaminated. One SHAM patient was excluded for unblinding, two SHAM patients were institutionalized during the study; two other SHAM patients had failed lumbar punctures.

Neurofilament light chain (NfL) is a marker of axonal degeneration and is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD. There is a strong relationship with cerebrospinal fluid (CSF) NfL, suggesting that these biomarker modalities reflect the same pathological process. The change score was determined by calculating the ratio of week CSF NfL over baseline CSF NfL. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in CSF NfL compared to baseline.

Outcome measures

Measure	Acitve PBM n=4 Participants This arm will receive active photobiomodulation (PBM), delivered with the Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Vielight Neuro Gamma: The Vielight Neuro Gamma is headset that delivers transcranial (through the scalp and skull) and intranasal (through the nose) near infrared (NIR) light. The device is engineered for increased efficacy and easy domestic use for comprehensive brain photobiomodulation (PBM). The NIR lights are pulsed at a 40 Hz rate, which correlates with electroencephalogram (EEG) gamma brain wave entrainment.	Sham PBM n=2 Participants This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.
Change in CSF Levels of NfL	0.6 Ratio Standard Deviation 0.3	0.7 Ratio Standard Deviation 0.06

Adverse Events

Acitve PBM

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Sham PBM

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Acitve PBM n=7 participants at risk This arm will receive active photobiomodulation (PBM), delivered with the Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Vielight Neuro Gamma: The Vielight Neuro Gamma is headset that delivers transcranial (through the scalp and skull) and intranasal (through the nose) near infrared (NIR) light. The device is engineered for increased efficacy and easy domestic use for comprehensive brain photobiomodulation (PBM). The NIR lights are pulsed at a 40 Hz rate, which correlates with electroencephalogram (EEG) gamma brain wave entrainment.	Sham PBM n=7 participants at risk This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks. Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.
Psychiatric disorders Agitation	0.00% 0/7 • 4 months	14.3% 1/7 • Number of events 1 • 4 months
Gastrointestinal disorders Diarrhea	0.00% 0/7 • 4 months	28.6% 2/7 • Number of events 2 • 4 months
General disorders Disorientation	14.3% 1/7 • Number of events 1 • 4 months	28.6% 2/7 • Number of events 2 • 4 months
General disorders Fever	14.3% 1/7 • Number of events 1 • 4 months	0.00% 0/7 • 4 months
Ear and labyrinth disorders Hearing loss	0.00% 0/7 • 4 months	14.3% 1/7 • Number of events 1 • 4 months
Renal and urinary disorders Hematuria	14.3% 1/7 • Number of events 1 • 4 months	0.00% 0/7 • 4 months
General disorders Hyponatremia	14.3% 1/7 • Number of events 1 • 4 months	14.3% 1/7 • Number of events 1 • 4 months
Musculoskeletal and connective tissue disorders Knee pain	14.3% 1/7 • Number of events 1 • 4 months	0.00% 0/7 • 4 months
Psychiatric disorders Paranoia	14.3% 1/7 • Number of events 1 • 4 months	14.3% 1/7 • Number of events 1 • 4 months
General disorders Syncope	14.3% 1/7 • Number of events 1 • 4 months	14.3% 1/7 • Number of events 1 • 4 months
Product Issues temporary device malfunction	28.6% 2/7 • Number of events 2 • 4 months	0.00% 0/7 • 4 months

Additional Information

Dr. Linda Chao

University of California, San Francisco & San Francisco VA Health Care System

Phone: 415-221-4810

Email: linda.chao@ucsf.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place