Neuro RX Gamma for Amnestic Mild Cognitive Impairment (aMCI)

Study Overview
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Brief Summary
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There are over 50 million people living with dementia, and by 2050, the number is expected to rise to 152 million worldwide. Mitochondrial dysfunction in the brain of MCI and AD patients is gaining prominence as a potential mechanism and thus treatment target. However, an effective therapy targeting mitochondrial function, is still missing. Photobiomodulation (PBM), is an innovative noninvasive technique that delivers transcranial near infrared light to the brain. PBM is thought to play a key role in enhancing mitochondrial function [especially in tissues with a high number of mitochondria (e.g.,brain)], by reducing oxidative stress and increasing ATP levels. PBM can be safely administered to awake outpatients and does not require general anesthesia or surgical implantation. Recent animal studies, and case studies suggest that PBM is a promising therapy for AD. However, due to the lack of placebo controls and objective blood and neuroimaging biomarkers, the effectiveness and mechanism of action of PBM (via enhancing mitochondrial function) in AD remains to be studied. Objectives: The investigators aim to evaluate cognitive changes and neural correlates associated with PBM in early amnestic MCI (aMCI) during a pilot feasibility study. Participants who meet study criteria will undergo a 6-week trial of home-used PBM using the Neuro Rx Gamma 6days/week, 20 minutes per session (n=20). All patients will undergo clinical and cognitive assessment, blood sample collection, and structural and resting state functional MRI scans in two timepoints; pre and post treatment. The longitudinal nature of the study will allow investigation of the PBM effect and its' neural correlates in aMCI via enhancement of mitochondrial function. The present study provides a unique opportunity to investigate the mitochondrial and neural mechanisms that may be involved in prevention or delay of cognitive decline in aMCI.

Detailed Description
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The experimental intervention will be the Vielight Neuro RX Gamma photobiomodulation device. The device uses 5 light emitting diodes (810nm wavelength). Diodes are placed on the skull at equidistance as well as intranasally to target relevant brain areas. No significant heat is generated, allowing for a sham device which will be indistinguishable from the intervention to the subjects. All subjects will be treated in 20 min sessions once daily for 6 days/week for 6 weeks. Subjects/caregivers will be taught to use the device at home and maintain a treatment diary. 20 min sessions of treatment (or sham) administered 6 days/week for 6 weeks by the subject. Baseline (T0) and 6-week (T2): 2 visits per subject pre and post treatment (at baseline, 6-week) for the following assessments: Mini-Mental State Examination (MMSE), CVLT Long delayed free recall, TMT B, TMT A, BVMT-R, Stroop neuropsychological screening, Pittsburgh sleep quality index, Beck's depression inventory, QOL-AD (Quality of life) , Mild Behavioral Impairment Checklist (MBI-C), Lactate, lactate/pyruvate blood test, Structural and functional MRI , One visits at week 3 (remote or in person) for safety assessment. Safety Endpoints: SAEs regardless of device causality, Device-related AEs, Rates of epistaxis and nasal infection.

Official Title
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A Pilot Study Evaluating the Feasibility, Safety, and Efficacy of the Vielight Neuro RX Gamma for the Treatment of Amnestic Mild Cognitive Impairment (aMCI)

Conditions
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MCI, Amnestic Mild Cognitive Disorder

Intervention / Treatment
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* Device: Neuro RX Gamma device
* Device: Sham Neuro RX Gamma device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age is greater than or equal to 50 years old. Meets the National Institute on Aging and Alzheimer's Association (NIA-AA) criteria for MCI due to Alzheimer's disease. Essentially normal functional activities as derived from the CDR. If receiving ongoing cholinesterase inhibitor therapy and/or memantine, must be on a stable dosage for at least the prior 3 months. MoCA score between 19 and 25 at screening assessment and impairment in learning and memory domain. Exclusion Criteria: Cannot tolerate blood draws. Claustrophobia (fear of small or enclosed spaces), that cannot tolerate MRI scanners. A pace-maker or other metal implants that would preclude safe use of MRI. DSM 5 diagnosis of alcohol or other substance use disorders within the past 12 months. Unstable medical illness, (e.g., uncontrolled diabetes mellitus or hypertension). Any history of stroke, seizures, MS, light sensitivity or Lyme disease. Any issues with ambulation, vision, or hearing which could, in the opinion of the investigator, interfere with their ability to complete assessments. Participant or caregiver does not speak English at a level necessary for the completion of the assessments. Has not completed at least a grade eight education, as necessary for the completion of the assessments. Currently participating in another clinical research study involving an investigational product. History of significant agitation and/or aggression, epileptic seizures. Current neurologic disease affecting cognition other than Alzheimer's disease. Photosensitivity reactions to sunlight or visible light (polymorphous light eruption, solar urticaria, persistent light reactivity). History of recurrent epistaxis within the last 24 weeks or currently taking major anti-coagulants (including warfarin, low molecular weight heparin) Increased skin sensitivity at the treatment site including active herpes simplex in the treatment area, history of keloid formation, or history of retinoid use in the past month. Pregnant or lactating or planning to become pregnant. Currently undergoing light therapy treatment. Any reason that, in the opinion of the investigator, might place a participant at unacceptable risk for participation in the trial.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized, single-blind trial. The trial will include patients with amnestic MCI who will be randomized in a 1:1 ratio to treatment with an active or sham Neuro RX Gamma device.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Neuro Rx Device<br>The active device will deliver light for the 20 minutes session duration. | Device: Neuro RX Gamma device<br>* The Neuro RX Gamma device is a portable, wearable, low level light therapy (LLLT) delivery device. The Vielight Neuro RX Gamma delivers a synchronized pulse frequency of 40 Hz from all LED clusters.<br>|
| Sham Comparator: Sham Neuro Rx Device<br>The Sham device is indistinguishable from the active device. The sham device will not deliver light for the 20 minutes session duration. | Device: Sham Neuro RX Gamma device<br>* The Sham device is indistinguishable from the active device. The sham device will not deliver light for the 20 minutes session duration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from pre- to post-treatment on mental status and cognitive function assessed by Mini-Mental State Examination (MMSE) | MMSE is a brief 30-point assessment | Baseline and 6 weeks post randomization | 
| Changes from pre- to post-treatment on verbal learning and memory assessed by California Verbal Learning Test II (CVLTII) | The Composite Score was created by grouping variables into domains and averaging the domains into a single Composite Score for each participant using: CVLTII - Total Recall Trials 1-5 CVLTII - d' Hits and False Alarms of recognition Yes/No responses CVLTII - Percent retained at long delay trial from trial 5 at immediate recall condition | Baseline and 6 weeks post randomization | 
| Changes from pre- to post-treatment on visuospatial memory assessed by Brief Visuospatial Memory Test Revised (BVMT-R) | The Composite Score was created by grouping variables into domains and averaging the domains into a single Composite Score for each participant using: BVMT-R - Total Recall Trials 1-3 BVMT-R - Percent Retained at Delayed Recall | Baseline and 6 weeks post randomization | 
| Changes from pre- to post-treatment on processing speed assessed by Trail Making Test (TMT)-part A | Trail Making A - Time per correct connection | Baseline and 6 weeks post randomization | 
| Changes from pre- to post-treatment on executive functioning assessed by Trail Making Test (TMT)-B/A and Stroop Color and Word Test (SCWT) | The Composite Score was created by grouping variables into domains and averaging the domains into a single Composite Score for each participant using: Trails Making Test - Ratio of time per correct connection B/A Stroop Neuropsychological Screening Test - Correct Responses at Color-Word condition | Baseline and 6 weeks post randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from pre- to post-treatment on Quality of life using QOL-AD | QOL-AD (Quality of life) is a 13-item questionnaire covering quality of life in different domains, such as living condition, physical health, relationship, and financial condition. Each item was rated on a 4-point scale, yielding a total score ranging from 13 to 52. | Baseline and 6 weeks post randomization | 
| Changes from pre- to post-treatment on peripheral Biomarkers assessed by blood | Blood lactate and lactate/pyruvate ratio will be measured due to their noted relationship with mitochondrial function. | Baseline and 6 weeks post randomization | 
| Changes from pre- to post-treatment on peripheral Biomarkers assessed by structural MRI (T1-weighted imaging) | Cortical thickness and subcortical volume | Baseline and 6 weeks post randomization | 
| Changes from pre- to post-treatment on peripheral Biomarkers assessed by structural MRI (Diffusion tensor imaging (DTI)) | fractional anisotropy (FA), and mean diffusivity (MD) measure | Baseline and 6 weeks post randomization | 
| Changes from pre- to post-treatment on peripheral Biomarkers assessed by functional MRI (resting state functional MRI scan) | Brain networks functional connectivity | Baseline and 6 weeks post randomization | 
| Changes from pre- to post-treatment on depressive symptoms using Beck's depression inventory | Beck's depression inventory is a 21-item multiple-choice self-report inventory rating inventory that measures characteristic attitudes and symptoms of depression. | Baseline and 6 weeks post randomization | 
| Changes from pre- to post-treatment on Pittsburgh sleep quality index | The measure consists of 19 individual items, creating 7 components that produce one global score | Baseline and 6 weeks post randomization | 
| Changes from pre- to post-treatment on Neuropsychiatric symptoms (NPS) using MBI-C (Mild Behavioral Impairment Checklist) | The MBI-C is a 34-item instrument and serves as a global and domain-specific NPS measure including early symptom presentations | Baseline and 6 weeks post randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MCI, Photobiomodulation, PBM, AD