Neuro RX Gamma for Amnestic Mild Cognitive Impairment (aMCI)

A Pilot Study Evaluating the Feasibility, Safety, and Efficacy of the Vielight Neuro RX Gamma for the Treatment of Amnestic Mild Cognitive Impairment (aMCI)

Over 50 million people worldwide are currently living with dementia-a number projected to rise to 152 million by 2050. Mitochondrial dysfunction in the brains of individuals with Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) has gained increasing attention as a potential mechanism and therapeutic target. However, no effective treatment specifically targeting mitochondrial function is currently available.

Photobiomodulation (PBM) is an innovative, non-invasive technique that delivers near-infrared light transcranially to the brain. PBM is believed to enhance mitochondrial function-particularly in tissues with high mitochondrial density such as the brain-by reducing oxidative stress and increasing ATP production. It can be safely administered to awake outpatients and does not require general anesthesia or surgical intervention. While preclinical and case studies suggest PBM may be beneficial in AD, the absence of placebo-controlled trials and objective biomarkers has limited understanding of its effectiveness and underlying mechanisms.

Objectives: This pilot feasibility study aims to assess cognitive outcomes and neural correlates associated with PBM in individuals with early amnestic MCI (aMCI). Participants who meet eligibility criteria (n = 20) will undergo a 6-week, home-based PBM intervention using the Neuro Rx Gamma device (6 days/week, 20 minutes/session). Clinical and cognitive assessments, blood sample collection, and structural and resting-state functional MRI scans will be conducted at two time points: baseline and post-treatment. These assessments will enable evaluation of PBM's effects on cognition and brain function, with particular focus on mitochondrial-related mechanisms.

This study offers a unique opportunity to investigate whether PBM can modulate mitochondrial and neural processes associated with cognitive decline in aMCI.

Study Overview

• Status: Completed
• Conditions: MCI; Amnestic Mild Cognitive Disorder
• Intervention / Treatment: Device: Neuro RX Gamma device; Device: Sham Neuro RX Gamma device

Detailed Description

Intervention:

The experimental intervention will be the Vielight Neuro RX Gamma photobiomodulation (PBM) device, which delivers near-infrared light via five light-emitting diodes (LEDs) operating at a wavelength of 810 nm. The LEDs are positioned equidistantly on the scalp and intranasally to target key brain regions. The device generates no significant heat, enabling the use of an indistinguishable sham device for placebo control.

All participants will self-administer 20-minute sessions once daily, six days per week, for six weeks. Subjects and/or caregivers will receive training to ensure proper at-home use and will be asked to maintain a treatment diary to monitor adherence.

Assessments:

Each participant will undergo two in-person visits-at baseline (T0) and post-intervention (week 7; T2)-to complete the following evaluations:

Mini-Mental State Examination (MMSE) California Verbal Learning Test - Long Delayed Free Recall (CVLT-LDFR) Trail Making Test A and B (TMT-A, TMT-B)

Pittsburgh Sleep Quality Index (PSQI) Mild Behavioral Impairment Checklist (MBI-C) Blood tests: lactate and lactate-to-pyruvate (L/P) ratio Structural and resting-state functional MRI, 1H-MRS, CBF An additional safety check will be conducted at week 1, 3, 5, and at the end of the study (either remotely or in person).

Safety Endpoints:

Serious adverse events (SAEs), regardless of device causality Device-related adverse events (AEs) Rates of epistaxis (nosebleeds) and nasal infections

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St Michael's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age is greater than or equal to 50 years old.
• Meets the National Institute on Aging and Alzheimer's Association (NIA-AA) criteria for MCI due to Alzheimer's disease.
• Essentially normal functional activities as derived from the CDR.
• If receiving ongoing cholinesterase inhibitor therapy and/or memantine, must be on a stable dosage for at least the prior 3 months.
• MoCA score between 19 and 25 at screening assessment and impairment in learning and memory domain.

Exclusion Criteria:

• Cannot tolerate blood draws.
• Claustrophobia (fear of small or enclosed spaces), that cannot tolerate MRI scanners.
• A pace-maker or other metal implants that would preclude safe use of MRI.
• DSM 5 diagnosis of alcohol or other substance use disorders within the past 12 months.
• Unstable medical illness, (e.g., uncontrolled diabetes mellitus or hypertension).
• Any history of stroke, seizures, MS, light sensitivity or Lyme disease.
• Any issues with ambulation, vision, or hearing which could, in the opinion of the investigator, interfere with their ability to complete assessments.
• Participant or caregiver does not speak English at a level necessary for the completion of the assessments.
• Has not completed at least a grade eight education, as necessary for the completion of the assessments.
• Currently participating in another clinical research study involving an investigational product.
• History of significant agitation and/or aggression, epileptic seizures.
• Current neurologic disease affecting cognition other than Alzheimer's disease.
• Photosensitivity reactions to sunlight or visible light (polymorphous light eruption, solar urticaria, persistent light reactivity).
• History of recurrent epistaxis within the last 24 weeks or currently taking major anti-coagulants (including warfarin, low molecular weight heparin)
• Increased skin sensitivity at the treatment site including active herpes simplex in the treatment area, history of keloid formation, or history of retinoid use in the past month.
• Pregnant or lactating or planning to become pregnant.
• Currently undergoing light therapy treatment.
• Any reason that, in the opinion of the investigator, might place a participant at unacceptable risk for participation in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Neuro Rx Device; The active device will deliver light for the 20 minutes session duration.	Device: Neuro RX Gamma device; The Neuro RX Gamma device is a portable, wearable, low level light therapy (LLLT) delivery device. The Vielight Neuro RX Gamma delivers a synchronized pulse frequency of 40 Hz from all LED clusters.
Sham Comparator: Sham Neuro Rx Device; The Sham device is indistinguishable from the active device. The sham device will not deliver light for the 20 minutes session duration.	Device: Sham Neuro RX Gamma device; The Sham device is indistinguishable from the active device. The sham device will not deliver light for the 20 minutes session duration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from pre- to post-treatment on mental status and cognitive function assessed by Mini-Mental State Examination (MMSE)	MMSE is a brief 30-point assessment	Assessed at baseline and post-intervention (week 7)
Changes from pre- to post-treatment on verbal learning and memory assessed by California Verbal Learning Test-II (CVLT-II)	The Composite Score was created by grouping variables into domains and averaging the domains into a single Composite Score for each participant using: CVLT-II - Total Recall Trials 1-5 CVLT-II - d' Hits and False Alarms of recognition Yes/No responses CVLT-II - Percent retained at long delay trial from trial 5 at immediate recall condition	Assessed at baseline and post-intervention (week 7)
Changes from pre- to post-treatment on processing speed assessed by Trail Making Test (TMT)-part A & B	Trail Making A - Time per correct connection	Assessed at baseline and post-intervention (week 7)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from pre- to post-treatment on peripheral blood-biomarkers assessed by blood	Blood lactate and lactate/pyruvate ratio will be measured due to their noted relationship with mitochondrial function.	Assessed at baseline and post-intervention (week 7)
Changes from pre- to post-treatment on structural MRI (T1-weighted imaging)	Cortical thickness and subcortical volume	Assessed at baseline and post-intervention (week 7)
Changes from pre- to post-treatment on brain metabolites (PCC)	N-acetylaspartate/creatine, lactate/creatine via single-voxel ¹H-MRS	Assessed at baseline and post-intervention (week 7)
Changes from pre- to post-treatment on resting state functional connectivity of the default mode network (DMN) via rs-fMRI	Brain networks functional connectivity	Assessed at baseline and post-intervention (week 7)
Changes from pre- to post-treatment on structural MRI (Diffusion tensor imaging - DTI)	fractional anisotropy (FA), and mean diffusivity (MD) measure	Assessed at baseline and post-intervention (week 7)
Changes from pre- to post-treatment on plasma biomarkers	markers of neuroinflammation (IL-6, IL-10), neurodegeneration (GFAP, NfL), tau pathology (phosphorylated Tau-217), and synaptic plasticity (Brain-Derived Neurotrophic Factor-BDNF)	Assessed at baseline and post-intervention (week 7)
Changes from pre- to post-treatment on Neuropsychiatric symptoms (NPS) using MBI-C (Mild Behavioral Impairment Checklist)	The MBI-C is a 34-item instrument and serves as a global and domain-specific NPS measure including early symptom presentations	Assessed at baseline and post-intervention (week 7)
Changes from pre- to post-treatment on Pittsburgh sleep quality index	The measure consists of 19 individual items, creating 7 components that produce one global score	Assessed at baseline and post-intervention (week 7)
Changes from pre- to post-treatment on cerebral blood flow (CBF)	CBF using pseudo-continuous arterial spin labeling (PCASL) -with a focus on DMN	Assessed at baseline and post-intervention (week 7)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from pre- to post-treatment on structural MRI (T1-weighted imaging)	Cortical thickness and subcortical volume	Assessed at baseline and post-intervention (week 7)
Changes from pre- to post-treatment on structural MRI (Diffusion tensor imaging - DTI)	fractional anisotropy (FA), and mean diffusivity (MD) measure	Assessed at baseline and post-intervention (week 7)
Changes from pre- to post-treatment on plasma biomarkers	markers of neuroinflammation (IL-6, IL-10), neurodegeneration (GFAP, NfL), tau pathology (phosphorylated Tau-217), and synaptic plasticity (Brain-Derived Neurotrophic Factor-BDNF)	Assessed at baseline and post-intervention (week 7)
Changes from pre- to post-treatment on Neuropsychiatric symptoms (NPS) using MBI-C (Mild Behavioral Impairment Checklist)	The MBI-C is a 34-item instrument and serves as a global and domain-specific NPS measure including early symptom presentations	Assessed at baseline and post-intervention (week 7)
Changes from pre- to post-treatment on Pittsburgh sleep quality index	The measure consists of 19 individual items, creating 7 components that produce one global score	Assessed at baseline and post-intervention (week 7)

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Investigators: Principal Investigator: Corinne Fischer, MD, Unity Health Toronto

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2023
• Primary Completion (Actual): February 3, 2025
• Study Completion (Actual): February 3, 2025

Study Registration Dates

• First Submitted: September 16, 2022
• First Submitted That Met QC Criteria: September 28, 2022
• First Posted (Actual): October 3, 2022

Study Record Updates

• Last Update Posted (Actual): July 24, 2025
• Last Update Submitted That Met QC Criteria: July 21, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: MCI; AD; Photobiomodulation; PBM
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognitive Dysfunction; Cognition Disorders
• Other Study ID Numbers: REB 22-128

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No