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

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ClinicalTrials.gov Identifier: NCT03405662
Recruitment Status : Recruiting
First Posted : January 23, 2018
Last Update Posted : October 1, 2018
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 goal of this study is to determine if PBM administered transcranially (through the scalp and skull) and intranasally (inside the nose) has an effect on cognitive function and behavioral symptoms in people with Alzheimer's disease (AD). The study will also examine whether PBM has an effect on biomarkers of AD in the blood and spinal fluid of patients with 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.

One aim of the study is to examine the effect PMB on cognitive function and behavioral symptoms in patients with probable AD. A second aim 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]). The final aim of the study is to 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. Upon completion of the post-treatment assessments, the Sham-treated patients 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 the active PBM treatments.

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).

Cognitive and behavioral function will be assessed in all study participants at baseline and after 16 weeks of PBM. 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 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
Estimated Primary Completion Date : May 31, 2019
Estimated Study Completion Date : December 31, 2019

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.


Secondary Outcome Measures :
  1. Change in performance on Color Trails Test (CTT) [ Time Frame: Baseline to 16 weeks ]
    CTTis a non-verbal test of visual attention, graphomotor sequencing, and effortful executive processing abilities (i.e., sustained attention and set shifting).

  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 an interview with a study companion or qualified partner.

  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.

  4. Change in blood levels of MCP-1. [ Time Frame: Baseline to 16 weeks ]
    MCP-1 is a biomarker of neuroinflammation.

  5. Change in CSF levels of MCP-1 [ Time Frame: Baseline to 16 weeks ]
    MCP-1 is a biomarker of neuroinflammation.

  6. Change in blood levels of Aβ42. [ Time Frame: Baseline to 16 weeks ]
    Aβ42 is a biomarker of AD pathology.

  7. Change in CSF levels of Aβ42. [ Time Frame: Baseline to 16 weeks ]
    Aβ42 is a biomarker of AD pathology

  8. Change in blood levels of UCH-L1. [ Time Frame: Baseline to 16 weeks ]
    UCH-L1 is a biomarker of neurodegeneration.

  9. Change in CSF levels of UCH-L1. [ Time Frame: Baseline to 16 weeks ]
    UCH-L1 is a biomarker of neurodegeneration.

  10. Change in blood levels of BDNF. [ Time Frame: Baseline to 16 weeks ]
    BDNF is a neurotrophic factor, which supports the growth, survival, and differentiation of both developing and mature neurons.

  11. Change in CSF levels of BDNF [ Time Frame: Baseline to 16 weeks ]
    BDNF is a neurotrophic factor, which supports the growth, survival, and differentiation of both developing and mature neurons.



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


Contacts
Contact: Linda L Chao, PhD 415-221-4810 ext x24386 linda.chao@ucsf.edu
Contact: Julio C Rojas, MD, PhD 415-502-7341 Julio.Rojas-Martinez@ucsf.edu

Locations
United States, California
VA Health Care System Recruiting
San Francisco, California, United States, 94121
Contact: Linda L Chao, PhD    415-221-4810 ext 24386    linda.chao@ucsf.edu   
UCSF Memory and Aging Center Recruiting
San Francisco, California, United States, 94158
Contact: Julio C Rojas-Martinez, MD, PhD    415-502-7341    Julio.Rojas-Martinez@ucsf.edu   
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Linda L Chao, PhD University of California, San Francisco

Publications:

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

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders