Neuro RX Gamma for Amnestic Mild Cognitive Impairment (aMCI)

NCT ID: NCT05563298

Last Updated: 2025-07-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-28
• Study Completion Date: 2025-02-03

Brief Summary

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.

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

Conditions

MCI; Amnestic Mild Cognitive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Active Neuro Rx Device

The active device will deliver light for the 20 minutes session duration.

Group Type: ACTIVE_COMPARATOR

Neuro RX Gamma device

Intervention Type: 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 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.

Group Type: SHAM_COMPARATOR

Sham Neuro RX Gamma device

Intervention Type: DEVICE

The Sham device is indistinguishable from the active device. The sham device will not deliver light for the 20 minutes session duration.

Interventions

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.

Intervention Type: 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.

Intervention Type: DEVICE

Eligibility Criteria

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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 95 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Unity Health Toronto

OTHER

Sponsor Role: lead

Responsible Party

Corinne Fischer

Professor of Psychiatry, University of Toronto

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Corinne Fischer, MD

Role: PRINCIPAL_INVESTIGATOR

Unity Health Toronto

Locations

St Michael's Hospital

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

REB 22-128

Identifier Type: -

Identifier Source: org_study_id