Transcranial Photobiomodulation for Alzheimer's Disease

Recruiting at 2 trial locations

Overseen By Dan Iosifescu, MD, MSc

Age: 65+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must be taking: Memantine, Acetylcholinesterase inhibitors

Must not be taking: Narcotics, Anticholinergics, Antipsychotics

Disqualifiers: Other dementia, Stroke, Bipolar, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 28

Duration: 8 weeks

125 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, it mentions that medications affecting cognition, like narcotic analgesics and antipsychotic meds, are not allowed. Stable use of memantine or acetylcholinesterase inhibitors is permitted.

What data supports the effectiveness of the treatment Transcranial Photobiomodulation for Alzheimer's Disease?

Preliminary data suggests that transcranial photobiomodulation (t-PBM) may help improve thinking skills in people with early Alzheimer's disease and mild memory problems. Additionally, studies have shown that similar light therapies can protect brain cells and improve memory in animal models, indicating potential benefits for Alzheimer's treatment. ^{1 2 3 4 5}

How does the treatment Transcranial Photobiomodulation differ from other treatments for Alzheimer's disease?

Transcranial Photobiomodulation (t-PBM) is unique because it uses near-infrared light to penetrate the brain and stimulate cellular processes, potentially improving blood flow and cognitive function. Unlike traditional drug treatments, t-PBM is non-invasive and focuses on reducing inflammation and oxidative stress, which are linked to Alzheimer's disease. ^{1 3 6 7 8}

What is the purpose of this trial?

This multi-site study will be the first to evaluate the dose-dependent effects of t-PBM in amnestic Mild Cognitive Impairment (aMCI) and early Alzheimer's Disease (AD) (CDR of 0.5-1, FAST 1-4; age 65-85) in a randomized clinical trial of 8 weeks of t-PBM vs. sham. At baseline, all subjects will complete initial neuropsychological testing. To elucidate mechanisms of action of t-PBM, prior to treatment, subjects will undergo neuroimaging related to critical features of AD: tau 18F MK-6240 load (PET), measures of brain bioenergetics (31P-MRS), and functional connectivity (rs-fMRI). After undergoing target engagement testing (t-PBM session performed during fMRI to detect BOLD changes with active t-PBM), subjects will then be randomized to t-PBM/sham and complete 24 t-PBM/sham treatments, \~11 min per day, 3 days per week, for 8 weeks. t-PBM will be administered via continuous, 808 nm wavelength laser delivery to the forehead bilaterally (at standard EEG electrode positions F4, F3).

Research Team

Dan Iosifescu, MD

Principal Investigator

NYU Langone Health and Nathan Kline Institute

Ricardo Osorio, MD

Principal Investigator

NYU Langone Health and Nathan Kline Institute

Paolo Cassano, MD, PhD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for people aged 65-85 with mild cognitive impairment or early Alzheimer's, who have at least a high school education and can consent to the study. Participants need a relative to confirm reports and must fit comfortably in imaging scanners without claustrophobia or metal implants that interfere with MRI.

Inclusion Criteria

I have mild memory loss that affects my daily life, but I am not severely impaired.

Have at least a high school diploma / 12 years education

Able to give written informed consent and follow study procedures.

Exclusion Criteria

A family member had dementia before turning 60.

I have no significant abnormal lab results or physical exam findings.

You are afraid of small spaces or have metal objects in your body that would prevent you from having an MRI scan.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Initial neuropsychological testing and neuroimaging to assess critical features of Alzheimer's Disease

1 week

1 visit (in-person)

Treatment

Participants receive 24 t-PBM/sham treatments, approximately 11 minutes per day, 3 days per week

8 weeks

24 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Transcranial Photobiomodulation

Trial Overview The TRAP-AD study tests if tPBM (a type of light therapy) helps brain function in those with memory issues due to aging. It involves daily sessions over 8 weeks, comparing active tPBM against a sham treatment while monitoring changes through advanced brain scans like PET and fMRI.

Participant Groups

Group I: Transcranial Photobiomodulation (t-PBM) Experimental Treatment 2 Interventions

Group II: Sham Placebo Group 2 Interventions

Transcranial Photobiomodulation is already approved in United States, European Union for the following indications:

Approved in United States as Transcranial Photobiomodulation for:

• Not approved for any indication; under investigation for Alzheimer's Disease and Mild Cognitive Impairment

Approved in European Union as Transcranial Photobiomodulation for:

• Not approved for any indication; under investigation for Alzheimer's Disease and Mild Cognitive Impairment

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

LiteCure LLC

Industry Sponsor

Trials

4

Recruited

190+

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]

Transcranial laser therapy using 808-nm continuous-wave laser light was found to be safe in healthy Sprague-Dawley rats, with no significant differences in clinical hematology or brain histopathology compared to sham controls after one year.

Both single and multiple applications of the laser treatment did not induce any toxic effects or abnormalities, suggesting its potential for long-term use in treating neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of single and multiple infrared transcranial laser treatments in Sprague-Dawley rats. McCarthy, TJ., De Taboada, L., Hildebrandt, PK., et al.[2019]

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]

Transcranial photobiomodulation (PBM) using NIR light has shown promising results in treating traumatic brain injury (TBI) in mice, leading to improved memory and learning, as well as increased neuroprogenitor cells and synaptogenesis in the brain.

The mechanism of action involves photon absorption in mitochondria, which activates signaling pathways that enhance protective gene expression, suggesting that PBM could have broader applications for various neurological conditions beyond TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photobiomodulation and the brain: a new paradigm. Hennessy, M., Hamblin, MR.[2020]

Near-infrared laser therapy (NIRLT) is being studied as a potential treatment for acute ischemic stroke patients in a pivotal phase III trial (NEST-3), focusing on its neuroreparatory and neuroprotective effects.

The review discusses the theoretical background and experimental studies supporting NIRLT, indicating its promise in clinical applications for stroke recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Near-infrared laser treatment of acute stroke: from bench to bedside]. Schellinger, PD., Köhrmann, M.[2021]

Photobiomodulation therapy has shown potential in reducing inflammation, oxidative stress, and cell death caused by amyloid beta in Alzheimer's disease, based on a systematic review of 10 studies conducted between 2008 and 2019.

The therapy also appears to restore mitochondrial function and improve cognitive behavior, suggesting it could be a promising non-pharmacological intervention for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Potential of Photobiomodulation In Alzheimer's Disease: A Systematic Review. Cardoso, FDS., Lopes Martins, RÁB., Gomes da Silva, S.[2021]

Transcranial photobiomodulation therapy (tPBMT) uses near infrared light to stimulate brain cells, potentially improving cognitive function in conditions like Alzheimer's disease and canine cognitive dysfunction.

This review highlights the promising effects of tPBMT observed in both animal models and human trials, suggesting it could be a beneficial treatment for cognitive decline in both humans and dogs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial photobiomodulation (laser) therapy for cognitive impairment: A review of molecular mechanisms and potential application to canine cognitive dysfunction (CCD). Dewey, CW., Brunke, MW., Sakovitch, K.[2022]

Photobiomodulation (PBM), which uses red or near-infrared light, shows promise as a non-invasive treatment for Alzheimer's disease (AD) and dementia, potentially stimulating healing and improving cognitive function.

While many clinical trials for AD treatments have failed, preliminary studies on tPBM in animal models and limited human trials suggest it may offer a new therapeutic approach worth further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photobiomodulation for Alzheimer's Disease: Has the Light Dawned? Hamblin, MR.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Long-term safety of single and multiple infrared transcranial laser treatments in Sprague-Dawley rats. [2019]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

Photobiomodulation and the brain: a new paradigm. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

[Near-infrared laser treatment of acute stroke: from bench to bedside]. [2021]

6. Iran pubmed.ncbi.nlm.nih.gov

Therapeutic Potential of Photobiomodulation In Alzheimer's Disease: A Systematic Review. [2021]

7. Libya pubmed.ncbi.nlm.nih.gov

Transcranial photobiomodulation (laser) therapy for cognitive impairment: A review of molecular mechanisms and potential application to canine cognitive dysfunction (CCD). [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Photobiomodulation for Alzheimer's Disease: Has the Light Dawned? [2020]