Transcranial Photobiomodulation for Alzheimer's Disease

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called transcranial photobiomodulation (t-PBM) to determine its effectiveness for people with early Alzheimer's Disease or mild memory problems. Participants will receive either the actual treatment or a sham version to compare effects. The trial aims to understand how t-PBM might improve brain function by using light to stimulate specific brain areas. Individuals experiencing mild memory issues related to Alzheimer's and who can follow study procedures might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to early findings on its potential benefits.

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 prior data suggests that transcranial photobiomodulation is safe for Alzheimer's patients?

Research has shown that transcranial photobiomodulation (t-PBM) is generally safe. Studies have found that t-PBM neither damages the brain nor affects cognitive abilities. Similar treatments, such as transcranial low-level laser therapy, have also demonstrated safety and positive effects on the brain.

No serious side effects have been reported with t-PBM, making it a promising option for clinical trial participants. However, as with any treatment, staying informed and discussing concerns with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Transcranial Photobiomodulation (t-PBM) is unique because it uses light therapy to potentially improve brain function in Alzheimer's patients. Unlike standard treatments like cholinesterase inhibitors and memantine that primarily address symptoms, t-PBM aims to stimulate brain cells by delivering light energy directly to the brain. Researchers are excited because this method could enhance brain metabolism and neuroprotection, offering a novel approach that targets the disease's underlying mechanisms rather than just its symptoms. This could open the door to more effective management of Alzheimer's disease.

What evidence suggests that transcranial photobiomodulation might be an effective treatment for Alzheimer's Disease?

Research has shown that transcranial photobiomodulation (t-PBM), a treatment available to participants in this trial, might help with memory and thinking problems related to Alzheimer's Disease. Studies have found that t-PBM can improve memory and decision-making, areas often affected by Alzheimer's. The treatment uses low-level laser light on the head to potentially boost brain function without causing harm. It is non-invasive, meaning it doesn't involve surgery, and it is affordable. Early results suggest it could be a promising option for people with early Alzheimer's or mild memory issues. ^{1 2 3 5 6}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10840571/

Transcranial photobiomodulation for brain diseases: review of ... Transcranial photobiomodulation (tPBM) is a promising technology for treating brain diseases, due to its effectiveness, non-invasiveness, and affordability.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X24001955

Transcranial low-level laser stimulation in the near-infrared ... Our data indicate that 1064 nm laser tPBM does not induce adverse effects on brain structure or function, nor does it impair cognitive abilities.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5180077/

Transcranial Low-Level Laser (Light) Therapy for Brain Injury Low-level laser therapy (LLLT) or photobiomodulation (PBM) is a possible treatment for brain injury, including traumatic brain injury (TBI).

4. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03988-w

Advances in photobiomodulation for cognitive improvement by ... In the field of cognition-related disorders, studies have shown that transcranial photobiomodulation improves executive performance, memory, ...

5. jneuropsychiatry.org jneuropsychiatry.org/peer-review/transcranial-lowlevel-laser-therapy-for-depression-and-alzheimers-disease.pdf

Transcranial Low-Level Laser Therapy for Depression and ... LLLT applies low-powered red or near-infrared (NIR) laser light (1-500 mW of power levels and 600-1100 nm of wavelengths) to stimulate a biological response [1] ...

6. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2770551

Effect of Transcranial Low-Level Light Therapy vs Sham ... The results of this clinical trial show that transcranial LLLT is feasible, safe, and affects the brain in a measurable manner.