Neuro RX Gamma for Amnestic Mild Cognitive Impairment (aMCI)

NCT05563298 | Completed Early Phase 1

• 1 other identifier: REB 22-128
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

MCI; Amnestic Mild Cognitive Disorder

Keywords

MCI; Photobiomodulation; PBM; AD

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (9)

• Changes from pre- to post-treatment on peripheral blood-biomarkers assessed by blood

  Assessed at baseline and post-intervention (week 7)

• Changes from pre- to post-treatment on plasma biomarkers

  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)

  Assessed at baseline and post-intervention (week 7)

• Changes from pre- to post-treatment on structural MRI (T1-weighted imaging)

  Assessed at baseline and post-intervention (week 7)

• Changes from pre- to post-treatment on brain metabolites (PCC)

  Assessed at baseline and post-intervention (week 7)

Study Arms (2)

Active Neuro Rx Device

ACTIVE COMPARATOR

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

Device: Neuro RX Gamma device

Sham Neuro Rx Device

SHAM COMPARATOR

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

Interventions

Neuro RX Gamma device 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.

Active Neuro Rx Device

Sham Neuro RX Gamma device DEVICE

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

Sham Neuro Rx Device

Eligibility Criteria

• Age: 50 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Unity Health Toronto: lead

Study Sites (1)

St Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Study Officials

• Corinne Fischer, MD

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: This is a randomized, single-blind trial. The trial will include patients with amnestic MCI who will be randomized in a 1:1 ratio to treatment with an active or sham Neuro RX Gamma device.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry, University of Toronto

Model Details: This is a randomized, single-blind trial. The trial will include patients with amnestic MCI who will be randomized in a 1:1 ratio to treatment with an active or sham Neuro RX Gamma device.

Study Record Dates

• First Submitted: September 16, 2022
• First Posted: October 3, 2022
• Study Start: March 28, 2023
• Primary Completion: February 3, 2025
• Study Completion: February 3, 2025
• Last Updated: July 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)