Clinical trial NCT03405662: Impact of Photobiomodulation (PBM) on Biomarkers of Alzheimer's Disease
Official title: Examining the Impact of Photobiomodulation on Cognition, Behavior, and Biomarkers of Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alzheimer Disease
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2018-01-23
Enrollment: 23
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants randomized to the "Active PBM" group will use an active Vielight Neuro device, for 16 weeks, once every other day (e.g., Mon, Wed, Fri) for 20 minutes.

Participants randomized to the "Sham PBM" group will use a a sham Vielight Neuro device, for 16 weeks, once every other day (e.g., Mon, Wed, Fri) for 20 minutes.

All study participants will undergo cognitive and behavioral assessments, blood draw, and lumbar puncture at baseline (before using Vielight Neuro Gamma device) and after 16 weeks of using the Vielight Neuro Gamma device.

Upon completion of the post-16 week assessments, blood draw, and lumbar puncture, patients randomized to the Sham PBM group will be offered an opportunity to use an active Vielight Neuro Gamma device for 16 weeks. We will assess cognition and behavioral symptoms in Sham patients who opt to undergo active PBM 16 weeks after they start active PBM treatments.
Primary purpose: TREATMENT

Brief summary: Photobiomodulation (PBM) describes the use of near-infrared light (which is not visible to the eye) to heal and protect tissue that has either been injured, is degenerating, or else is at risk of dying. Research suggests that the light delivered during PBM enhances the body's biochemical ability to store and use energy and increase blood flow, which triggers the body's natural healing processes. The primary goal of this study is to determine if PBM administered transcranially (through the scalp and skull) and intranasally (inside the nose) with a commercially available device is safe and tolerable for patients with mild-to-moderate Alzheimer's disease (AD). Secondary goals are to examine whether tPBM has an effect on cognitive function and behavioral symptoms in patients with AD and whether tPBM has an effect on fluid biomarkers of AD. A biomarker is a specific physical trait used to measure the progress of a disease or condition.

Detailed description: Alzheimer's disease (AD), the most common form of dementia, is characterized by the loss of higher brain function such as memory, problem-solving abilities, and language. Photobiomodulation (PBM) describes a kind of light therapy that uses red or near-infrared light to stimulate, heal, regenerate, and protect tissue that has either been injured, is degenerating, or else is at risk of dying. The pathological hallmarks of AD include senile plaques rich in β-amyloid (Aβ) peptide and neurofibrillary tangles composed of hyperphosphorylated tau (p-tau). In animal models of AD, PBM reduces the size and number of brain Aβ plaques, p-tau, and neurofibrillary tangles. PBM also mitigates behavioral deficits in transgenic AD mouse models and humans with dementia. The goal of this sham-controlled pilot trial is to investigate the effects of PBM on the cognitive function, behavioral symptoms, and fluid (i.e., cerebrospinal fluid (CSF) and blood) biomarkers of AD pathology including amyloid burden, tangle pathology, axonal injury, microglia activation/inflammation, and neurotrophic factors in 16 patients with biomarkers-supported probable Alzheimer's dementia, according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.

The main goal of the study is to examine the safety and tolerability of home administered transcranial photobiomodulation (tPBM) with a commercially available device in patients with mild-to-moderate AD. Another goal of the study is to examine the effect PMB on cognitive function and behavioral symptoms in patients with probable AD. The study's final goal is to examine the effects of 16 weeks of PBM on fluid biomarkers of inflammation (i.e., monocyte chemoattractant protein 1 and 3 \[MCP-1 and MCP-3\] and macrophage inflammatory protein 1β \[MIP-1β\]), neurodegeneration (i.e., ubiquitin carboxyl-terminal hydrolase isozyme L1 \[UCH-L1\] and neurofilament light chain \[NfL\]) and neurotrophic factors (i.e., vascular endothelial growth factor \[VEGF\] and brain-derived neurotrophic factor \[BDNF\]). We will also explore the relationship between cognitive and behavioral changes after 16 weeks of PBM with changes in biomarkers of inflammation, neurotrophic factors, and neurodegeneration.

Sixteen patients with biomarkers-supported probable Alzheimer's dementia will be enrolled and randomly assigned to an active or sham PBM group. All patients will be asked to use the Vielight Neuro Gamma (real or sham) device for 20 minutes/day, every other day, for 16 weeks. Randomization with blind assignment will be determined by a computer-generated random allocation. We will assess safety and tolerability by comparing adverse events (AD) in each group. Cognition, behavioral symptoms, and biomarker measures will be assessed in all study participants at baseline and after 16 weeks of PBM. Biomarkers will be obtained through a blood draw and lumbar puncture. A lumbar puncture (also called a spinal tap) is a procedure to collect cerebrospinal fluid, or CSF), which surrounds the brain and spinal cord. During a lumbar puncture, a needle is carefully inserted into the spinal canal low in the back (lumbar area).

Study partners (e.g., caregivers) will be asked to answer questions about the study participant's memory and daily functioning at baseline and after 16 weeks of PBM. Study partners will also be trained and ask to help the study partners administer PBM treatments with the Vielight Neuro Gamma device at home for 16 weeks.

Eligibility criteria: Inclusion Criteria (for participants with AD):

* Diagnosis of AD supported by AD biomarkers (CSF or amyloid PET)
* Mini-Mental State Exam (MMSE) score \> 13
* fluent in English
* has a reliable caregiver/study partner who can help administer and log PBM use
* no history of stroke or seizures
* willing to undergo 2 lumbar punctures approximately 4 months apart
* legally authorized representative consent

Exclusion Criteria: (for participants with AD)

* lack of assent to study procedures
* terminal illness (i.e., life expectancy \< 1 year)
* started dementia medication (i.e., cholinesterase inhibitor or memantine) within the past 3 months or planning to start new dementia medication
* current participation in another research study that could potentially confound current study (e.g., medication or behavioral intervention)
* MMSE \< 13
* history of structural brain lesions or stroke temporally related to the onset or worsening of cognitive impairment
* history of head trauma associated with injury-onset cognitive complaints or loss of consciousness for 10 minutes or longer.

Inclusion Criteria (for study partners):

* ability to answer questions about the primary participant's memory, behaviors, and activities of daily living
* willingness to help primary participant use and log the use of the Vielight Neuro Gamma device every other day for 16 weeks
* fluent in English

Exclusion Criteria (for study partners):

* major neurological or psychiatric condition
* terminal illness (i.e., life expectancy \< 1 year)
* evidence of cognitive impairment
* inability to consent to study procedure

Primary outcomes:
measure: Change in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog)
timeFrame: Baseline to 16 weeks
Secondary outcomes:
measure: Change in Performance on Color Trails Test (CTT2/CTT1 Index)
timeFrame: Baseline to 16 weeks
measure: Change on the Neuropsychiatriac Inventory (NPI)
timeFrame: Baseline to 16 weeks
measure: Change on the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL)
timeFrame: Baseline to 16 weeks
measure: Change in Plasma Levels of Aβ42
timeFrame: Baseline to 16 weeks
measure: Change in CSF Levels of Aβ42.
timeFrame: Baseline to 16 weeks
measure: Change in Plasma Levels of Tau.
timeFrame: Baseline to 16 weeks
measure: Change in CSF Levels of Tau
timeFrame: Baseline to 16 weeks
measure: Change in Plasma Levels of Neurofilament Light Chain (NfL)
timeFrame: Baseline to 16 weeks
measure: Change in CSF Levels of NfL
timeFrame: Baseline to 16 weeks
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: VA Health Care System
state: California
city: San Francisco
country: United States
facility: UCSF Memory and Aging Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: Linda L Chao, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: De Taboada L, Yu J, El-Amouri S, Gattoni-Celli S, Richieri S, McCarthy T, Streeter J, Kindy MS. Transcranial laser therapy attenuates amyloid-beta peptide neuropathology in amyloid-beta protein precursor transgenic mice. J Alzheimers Dis. 2011;23(3):521-35. doi: 10.3233/JAD-2010-100894.
citation: Purushothuman S, Johnstone DM, Nandasena C, Mitrofanis J, Stone J. Photobiomodulation with near infrared light mitigates Alzheimer's disease-related pathology in cerebral cortex - evidence from two transgenic mouse models. Alzheimers Res Ther. 2014 Jan 3;6(1):2. doi: 10.1186/alzrt232. eCollection 2014.
citation: Berman MH, Halper JP, Nichols TW, Jarrett H, Lundy A, Huang JH. Photobiomodulation with Near Infrared Light Helmet in a Pilot, Placebo Controlled Clinical Trial in Dementia Patients Testing Memory and Cognition. J Neurol Neurosci. 2017;8(1):176. doi: 10.21767/2171-6625.1000176. Epub 2017 Feb 28.
citation: Sommer AP, Bieschke J, Friedrich RP, Zhu D, Wanker EE, Fecht HJ, Mereles D, Hunstein W. 670 nm laser light and EGCG complementarily reduce amyloid-beta aggregates in human neuroblastoma cells: basis for treatment of Alzheimer's disease? Photomed Laser Surg. 2012 Jan;30(1):54-60. doi: 10.1089/pho.2011.3073. Epub 2011 Oct 26.
citation: Grillo SL, Duggett NA, Ennaceur A, Chazot PL. Non-invasive infra-red therapy (1072 nm) reduces beta-amyloid protein levels in the brain of an Alzheimer's disease mouse model, TASTPM. J Photochem Photobiol B. 2013 Jun 5;123:13-22. doi: 10.1016/j.jphotobiol.2013.02.015. Epub 2013 Mar 22.