Laser Therapy for Mild Cognitive Impairment

(PBMCI-Prime Trial)

Recruiting at 1 trial location

Overseen By Corinne Fischer, MD, FRCP(C)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Unity Health Toronto

Must be taking: Cholinesterase inhibitors, Memantine

Must not be taking: Major anti-coagulants

Disqualifiers: Stroke, Seizures, MS, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Mild cognitive impairment (MCI) is a transitional risk state that occurs between the normal aging process and Alzheimer's dementia (AD). On average 32% of patients with MCI will progress to dementia, 62% will stay stable, and about 6% will return to normal cognition at subsequent visits. Current treatment for MCI includes cholinesterase inhibitors (donepezil, galantamine and rivastigmine), and NMDA receptor antagonists (memantine) which delay or slow the worsening of symptoms and treat cognitive symptoms (memory loss, confusion, and problems with thinking and reasoning). Despite currently ongoing drug studies and modest clinical benefits of currently approved drug treatments, there continues to remain a need for treatments for long term symptomatic improvement of MCI with fewer and less severe side effects. Photobiomodulation (PBM) therapy also called low-level laser (or light) therapy (LLLT) is a safe, non-invasive, non-thermal (no significant heat is generated) method of therapy which uses either visible red or near-infrared (NIR) light to stimulate, heal and repair damaged or dying tissue cells. This study proposes to use the Neuro RX Gamma device (version 2) to deliver NIR light energy to particular brain regions which are dysfunctional in MCI participants.

Do I have to stop taking my current medications for the trial?

If you are taking cholinesterase inhibitors or memantine, you must be on a stable dosage for at least the prior 3 months to participate in the trial. The protocol does not specify about other medications, so it's best to discuss with the trial team.

Is laser therapy safe for humans?

Research on laser therapy, also known as photobiomodulation, suggests it is generally safe for use in humans, as it is noninvasive and has fewer side effects compared to drugs. Studies in animal models have shown it can reduce inflammation and oxidative stress, which are linked to Alzheimer's disease, without significant safety concerns. ^{1 2 3 4 5}

How does the Neuro RX Gamma (v2) treatment differ from other treatments for mild cognitive impairment?

Neuro RX Gamma (v2) uses a unique approach called transcranial photobiomodulation, which involves shining near-infrared light on the brain to improve mitochondrial function and increase blood flow, potentially enhancing cognitive function. This method is different from traditional drug treatments as it targets the brain's energy production and reduces inflammation without using medication. ^{2 5 6 7 8}

Eligibility Criteria

This trial is for individuals with mild cognitive impairment (MCI) or early Alzheimer's disease. Participants should be experiencing memory loss, confusion, and difficulty with thinking and reasoning. Those who have other serious medical conditions that could interfere with the study or are currently receiving certain treatments for MCI may not qualify.

Inclusion Criteria

Essentially normal functional activities as derived from the CDR

I have been on a stable dose of cholinesterase inhibitor or memantine for 3 months.

MoCA score between 19 and 25 at screening assessment and impairment in learning and memory domain

Exclusion Criteria

Presence of 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

I have no problems with walking, seeing, or hearing that would affect medical tests.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo an 8-week trial of home-use PBM using the Neuro RX Gamma (v2) device, 6 days/week, 20 minutes per session

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cognitive assessments and blood-based biomarker tests

4 weeks

Treatment Details

Interventions

• Neuro RX Gamma (v2)

Trial Overview The trial is testing a device called Neuro RX Gamma (v2), which uses near-infrared light to stimulate brain regions affected by MCI. It compares the effects of an active tPBM device against a sham (inactive) device to see if it can improve symptoms related to cognitive decline.

Participant Groups

Group I: Active group Active Control 1 Intervention

The active group will undergo a 8-week trial of home-use tPBM using the active Neuro RX Gamma (v2) device, 6 days/week, 20 minutes per session.

Group II: Sham group Placebo Group 1 Intervention

The sham group will undergo a 8-week trial of home-use PBM using the sham Neuro RX Gamma (v2) device, 6 days/week, 20 minutes per session.

Who Is Running the Clinical Trial?

Unity Health Toronto

Lead Sponsor

Trials

572

Recruited

470,000+

The W. Garfield Weston Foundation

Collaborator

Trials

4

Recruited

210+

HILARY AND GALEN WESTON FOUNDATION

Collaborator

Findings from Research

This study will evaluate the efficacy and safety of transcranial photobiomodulation (t-PBM) in improving cognitive function in participants with amnestic mild cognitive impairment (aMCI) and early Alzheimer's disease (AD) through 24 treatment sessions over 8 weeks.

The research aims to explore the underlying brain mechanisms of t-PBM, including its effects on tau burden and mitochondrial function, as well as its ability to increase blood flow in the prefrontal cortex, which could provide insights into how this therapy may enhance cognitive performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol Report on the Transcranial Photobiomodulation for Alzheimer's Disease (TRAP-AD) Study. Iosifescu, DV., Song, X., Gersten, MB., et al.[2023]

The RGn500 device, which combines photonic and magnetic emissions, showed a neuroprotective effect in a mouse model of Alzheimer's disease when applied daily for 10 minutes, leading to memory restoration and normalization of key Alzheimer's markers.

This treatment demonstrated similar therapeutic efficacy to traditional pharmacological approaches, suggesting it could be a promising alternative for managing Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroprotective effect of a new photobiomodulation technique against Aβ25-35 peptide-induced toxicity in mice: Novel hypothesis for therapeutic approach of Alzheimer's disease suggested. Blivet, G., Meunier, J., Roman, FJ., et al.[2022]

In a study involving 5 patients with mild to moderately severe dementia, treatment with near-infrared photobiomodulation (PBM) therapy for 12 weeks led to significant cognitive improvements, as measured by the Mini-Mental State Exam (MMSE) and Alzheimer's Disease Assessment Scale (ADAS-cog).

The therapy was associated with positive changes in daily functioning, sleep quality, and reduced anxiety, with no reported negative side effects, highlighting PBM's potential as a safe and effective home treatment option for dementia and Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significant Improvement in Cognition in Mild to Moderately Severe Dementia Cases Treated with Transcranial Plus Intranasal Photobiomodulation: Case Series Report. Saltmarche, AE., Naeser, MA., Ho, KF., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Low energy laser light (632.8 nm) suppresses amyloid-β peptide-induced oxidative and inflammatory responses in astrocytes. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Low-level laser therapy for beta amyloid toxicity in rat hippocampus. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Microglia modulation with 1070-nm light attenuates Aβ burden and cognitive impairment in Alzheimer's disease mouse model. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Photobiomodulation Using a Low-Level Light-Emitting Diode Improves Cognitive Dysfunction in the 5XFAD Mouse Model of Alzheimer's Disease. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Protocol Report on the Transcranial Photobiomodulation for Alzheimer's Disease (TRAP-AD) Study. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Neuroprotective effect of a new photobiomodulation technique against Aβ25-35 peptide-induced toxicity in mice: Novel hypothesis for therapeutic approach of Alzheimer's disease suggested. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Significant Improvement in Cognition in Mild to Moderately Severe Dementia Cases Treated with Transcranial Plus Intranasal Photobiomodulation: Case Series Report. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Illumination with 630 nm Red Light Reduces Oxidative Stress and Restores Memory by Photo-Activating Catalase and Formaldehyde Dehydrogenase in SAMP8 Mice. [2020]