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Impact of Photobiomodulation (PBM) on Biomarkers of Alzheimer's Disease (PBMbiomarker)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03405662
Recruitment Status : Completed
First Posted : January 23, 2018
Results First Posted : July 1, 2022
Last Update Posted : July 1, 2022
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco

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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Device: Vielight Neuro Gamma Other: Sham Vielight Neuro Gamma Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Blind assignment determined by a computer-generated random allocation schedule
Primary Purpose: Treatment
Official Title: Examining the Impact of Photobiomodulation on Cognition, Behavior, and Biomarkers of Alzheimer's Disease
Actual Study Start Date : August 16, 2018
Actual Primary Completion Date : January 1, 2021
Actual Study Completion Date : January 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Acitve PBM
This arm will receive active photobiomodulation (PBM), delivered with the Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks.
Device: Vielight Neuro Gamma
The Vielight Neuro Gamma is headset that delivers transcranial (through the scalp and skull) and intranasal (through the nose) near infrared (NIR) light. The device is engineered for increased efficacy and easy domestic use for comprehensive brain photobiomodulation (PBM). The NIR lights are pulsed at a 40 Hz rate, which correlates with electroencephalogram (EEG) gamma brain wave entrainment.

Sham Comparator: Sham PBM
This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks.
Other: Sham Vielight Neuro Gamma
The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.




Primary Outcome Measures :
  1. Change in Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog) [ Time Frame: Baseline to 16 weeks ]

    The ADAS-cog is the most popular cognitive testing instrument used in clinical trials of nootropics. It consists of 11 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities which are often referred to as the core symptoms of AD. Higher ADAS-cog scores indicate greater cognitive impairment.

    The changes score was determined by calculating the ratio of the ADAS-cog score at week 16 over the ADAS-cog score at baseline. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in ADAS-cog score compared to baseline.



Secondary Outcome Measures :
  1. Change in Performance on Color Trails Test (CTT2/CTT1 Index) [ Time Frame: Baseline to 16 weeks ]
    CTT is a non-verbal test of visual attention, graphomotor sequencing, and effortful executive processing abilities (i.e., sustained attention and set shifting). A higher index score indicates less cognitive flexibility, a lower ability to shift attention.

  2. Change on the Neuropsychiatriac Inventory (NPI) [ Time Frame: Baseline to 16 weeks ]

    NPI is a well-validated, reliable, multi-item instrument to assess psychopathology (e.g., behavioral symptoms) in AD based on a questionnaire completed by the participants' study partners. Higher scores indicate more symptoms and/or more severe symptoms.

    The changes score was determined by calculating the ratio of the week 16 NPI score over the baseline NPI score. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in NPI compared to baseline.


  3. Change on the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) [ Time Frame: Baseline to 16 weeks ]
    ADCS-ADL assesses the competence of patients with AD in basic and instrumental activities of daily living (ADLs). It can be completed by a caregiver in questionnaire format, or administered by a clinician/researcher as a structured interview with a caregiver. ADCS-ADL scores range from 0-53, with higher scores indicating greater independence. The changes score was determined by calculating the ratio of the week 16 ADCS-ADL score over the baseline ADCS-ADL score. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in ADCS-ADL compared to baseline.

  4. Change in Plasma Levels of Aβ42 [ Time Frame: Baseline to 16 weeks ]
    Although Aβ42 is present in plasma, it is unclear whether it originates from peripheral sources or from the brain. Because Aβ can be transported bidirectionally across the blood-brain barrier, it has been hypothesized that there may be an equilibrium between CSF and plasma pools of Aβ. Decreased levels of Aβ42 in CSF occurs in conjunction with cognitive decline. However, patients with mutations in chromosome 21 that cause early-onset familial AD and patients with trisomy 21 have increased levels of plasma Aβ42 before the onset of the symptoms of dementia. Therefore, it is possible that plasma Aβ42 levels increase with cognitive decline. The change score was determined by calculating the ratio of plasma Aβ42 at week 16 over the ADAS-cog score at baseline.

  5. Change in CSF Levels of Aβ42. [ Time Frame: Baseline to 16 weeks ]
    Aβ42 is a biomarker of AD pathology. CSF levels of Aβ42 decrease in conjunction with the cognitive decline. The change score was determined by calculating the ratio of CSF Aβ42 at week 16 over the ADAS-cog score at baseline. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in CSF levels of Aβ42 compared to baseline.

  6. Change in Plasma Levels of Tau. [ Time Frame: Baseline to 16 weeks ]
    Tau, the microtubule-associated protein, forms insoluble filaments that accumulate as neurofibrillary tangles in Alzheimer's disease (AD). Research suggests that plasma tau levels increased with AD severity. The change score was determined by calculating the ratio of the week 16 plasma tau over the baseline plasma tau levels. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in plasma tau compared to baseline.

  7. Change in CSF Levels of Tau [ Time Frame: Baseline to 16 weeks ]
    Tau forms insoluble filaments that accumulate as neurofibrillary tangles in AD. Increased levels of tau in CSF is a key characteristic of AD and is considered to result from neurodegeneration. The change score was determined by calculating the ratio of week 16 CSF tau over baseline CSF tau. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in CSF tau compared to baseline.

  8. Change in Plasma Levels of Neurofilament Light Chain (NfL) [ Time Frame: Baseline to 16 weeks ]
    Neurofilament light chain (NfL) is a marker of axonal degeneration and is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD. The change score was determined by calculating the ratio of week 16 plasma levels of NfL over the baseline levels of plasma NfL. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in plasma levels of NfL compared to baseline.

  9. Change in CSF Levels of NfL [ Time Frame: Baseline to 16 weeks ]
    Neurofilament light chain (NfL) is a marker of axonal degeneration and is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD. There is a strong relationship with cerebrospinal fluid (CSF) NfL, suggesting that these biomarker modalities reflect the same pathological process. The change score was determined by calculating the ratio of week CSF NfL over baseline CSF NfL. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in CSF NfL compared to baseline.



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03405662


Locations
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United States, California
VA Health Care System
San Francisco, California, United States, 94121
UCSF Memory and Aging Center
San Francisco, California, United States, 94158
Sponsors and Collaborators
University of California, San Francisco
Investigators
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Principal Investigator: Linda L Chao, PhD University of California, San Francisco
  Study Documents (Full-Text)

Documents provided by University of California, San Francisco:
Informed Consent Form  [PDF] February 18, 2020

Publications:

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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03405662    
Other Study ID Numbers: OsherRAP
First Posted: January 23, 2018    Key Record Dates
Results First Posted: July 1, 2022
Last Update Posted: July 1, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders