Transcranial Photobiomodulation (tPBM) in Alzheimer's Disease Study

Official title

A Longitudinal Study Investigating the Effects of Photobiomodulation (PBM) on Cognitive Function and Alzheimer's Disease (AD)-Related Biomarkers in Individuals With Mild Cognitive Impairment (MCI) or Dementia Due to AD

Overview

The purpose of this study is to see if a special light treatment, called photobiomodulation, can help people with memory problems such as Mild Cognitive Impairment or Mild Dementia due to Alzheimer's disease. The light is given to the forehead using an FDA-cleared medical device. This device is cleared to provide topical heating to elevate tissue temperature for temporary relief of muscle and joint pain, muscle spasm and stiffness associated with arthritis. It also increases blood circulation and relaxes muscle tissue. This device is being used "off-label," meaning it will be used in a way that is different than its cleared use. We want to learn whether this light treatment can improve executive function, and whether it changes certain inflammatory and neurodegeneration related signals in the blood. To do this, we will apply the photobiomodulation device to your forehead. We will also ask you questions and give you cognitive tests before and after light treatment. We will also collect blood samples before and after treatment.

Interventions

• Device Photobiomodulation
  1064nm transcranial photobiomodulation

Primary outcome measures

• NIH Toolbox [Time frame: Baseline measurements will be performed prior to intervention, post-treatment (week 5), and lastly at the 3-month follow-up visit]

Secondary outcome measures (6)

• Glial Fibrillary Acidic Protein (GFAP) [Time frame: Will be performed at baseline and at 3 month follow up]
• Neurofilament Light Chain (NfL) [Time frame: Baseline and 3-month follow up]
• Total Tau [Time frame: Baseline and 3-month follow up]
• Interferon-γ (IFN-γ) [Time frame: Baseline and 3-month follow up]
• Interleukin-1β (IL-1β) [Time frame: Baseline and 3-month follow up]
• Tumor Necrosis Factor-α (TNF-α) [Time frame: Baseline and 3-month follow up]

Eligibility criteria

Inclusion criteria

• Signed and dated informed consent form (either by subject or LAR)
• Willingness and ability to comply with all study procedures
• Age 55 to 89 years, inclusive
• Clinical diagnosis of Mild Cognitive Impairment or mild dementia (CDR Global = 0-1; MoCA 16-25) due to probable Alzheimer's disease diagnosis
• Ability to attend in-person sessions at Cedars-Sinai and adhere to weekly visits
• Stable dose of Alzheimer's disease medications (e.g., donepezil, rivastigmine, memantine, galantamine) for at least 4 weeks prior to enrollment, if applicable

Exclusion criteria

• Presence of significant neurological conditions other than AD (e.g., epilepsy, Parkinson, etc.)
• History of Seizures
• If patient holds neuroimaging showing space-occupying lesions
• If patient holds imaging with Fazekas greater than or equal to 3, more than 2 lacunar infarcts, and/or more than 5 microhemorrhages
• Current pregnancy or lactation (although unlikely in this population)
• Participation in another clinical trial or investigational drug within the past 30 days
• Active use of illicit substances or non-prescribed psychoactive drugs within the past 30 days.
• Severe dementia due to Alzheimer's disease or another etiology
• Physical or mental impairment that prevents the participant from complying with the cognitive testing battery.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 1 center

• CSMC — Los Angeles

Publications

• Zhu G, Tong Q, Ye X, Li J, Zhou L, Sun P, Liang F, Zhong S, Cheng R, Zhang J. Phototherapy for Cognitive Function in Patients With Dementia: A Systematic Review and Meta-Analysis. Front Aging Neurosci. 2022 Jun 30;14:936489. doi: 10.3389/fnagi.2022.936489. eCollection 2022. PMID 35847661
• Luo G, Zhang J, Song Z, Wang Y, Wang X, Qu H, Wang F, Liu C, Gao F. Effectiveness of non-pharmacological therapies on cognitive function in patients with dementia-A network meta-analysis of randomized controlled trials. Front Aging Neurosci. 2023 Mar 2;15:1131744. doi: 10.3389/fnagi.2023.1131744. eCollection 2023. PMID 36967820
• Chan AS, Lee TL, Yeung MK, Hamblin MR. Photobiomodulation improves the frontal cognitive function of older adults. Int J Geriatr Psychiatry. 2019 Feb;34(2):369-377. doi: 10.1002/gps.5039. Epub 2018 Dec 10. PMID 30474306
• Su M, Nizamutdinov D, Liu H, Huang JH. Recent Mechanisms of Neurodegeneration and Photobiomodulation in the Context of Alzheimer's Disease. Int J Mol Sci. 2023 May 25;24(11):9272. doi: 10.3390/ijms24119272. PMID 37298224
• Gonzalez-Lima, F. (2021). Neuroprotection and Neurocognitive Augmentation by Photobiomodulation. In: Opris, I., A. Lebedev, M., F. Casanova, M. (eds) Modern Approaches to Augmentation of Brain Function. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-030-54564-2_9
• Vargas E, Barrett DW, Saucedo CL, Huang LD, Abraham JA, Tanaka H, Haley AP, Gonzalez-Lima F. Beneficial neurocognitive effects of transcranial laser in older adults. Lasers Med Sci. 2017 Jul;32(5):1153-1162. doi: 10.1007/s10103-017-2221-y. Epub 2017 May 2. PMID 28466195
• Boyer D, Hu A, Warrow D, Xavier S, Gonzalez V, Lad E, Rosen RB, Do D, Schneiderman T, Ho A, Munk MR, Jaffe G, Tedford SE, Croissant CL, Walker M, Ruckert R, Tedford CE. LIGHTSITE III: 13-Month Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative (Dry) Age-Related Macular Degeneration Using the Lumithera Valeda Light Delivery System. Retina. 2024 Mar 1;44(3):487-497. PMID 37972955

Identifiers

NCT: NCT07224607 · STUDY00004349

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗