Clinical trial NCT05563298: Neuro RX Gamma for Amnestic Mild Cognitive Impairment (aMCI)
Official title: A Pilot Study Evaluating the Feasibility, Safety, and Efficacy of the Vielight Neuro RX Gamma for the Treatment of Amnestic Mild Cognitive Impairment (aMCI)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: MCI
Amnestic Mild Cognitive Disorder
Keywords: MCI
Photobiomodulation
PBM
AD
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
First posted: 2022-10-03
Enrollment: 20
Sex: ALL
Minimum age (years): 50
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes from pre- to post-treatment on mental status and cognitive function assessed by Mini-Mental State Examination (MMSE)
timeFrame: Baseline and 6 weeks post randomization
measure: Changes from pre- to post-treatment on verbal learning and memory assessed by California Verbal Learning Test II (CVLTII)
timeFrame: Baseline and 6 weeks post randomization
measure: Changes from pre- to post-treatment on visuospatial memory assessed by Brief Visuospatial Memory Test Revised (BVMT-R)
timeFrame: Baseline and 6 weeks post randomization
measure: Changes from pre- to post-treatment on processing speed assessed by Trail Making Test (TMT)-part A
timeFrame: Baseline and 6 weeks post randomization
measure: Changes from pre- to post-treatment on executive functioning assessed by Trail Making Test (TMT)-B/A and Stroop Color and Word Test (SCWT)
timeFrame: Baseline and 6 weeks post randomization
Secondary outcomes:
measure: Changes from pre- to post-treatment on Quality of life using QOL-AD
timeFrame: Baseline and 6 weeks post randomization
measure: Changes from pre- to post-treatment on peripheral Biomarkers assessed by blood
timeFrame: Baseline and 6 weeks post randomization
measure: Changes from pre- to post-treatment on peripheral Biomarkers assessed by structural MRI (T1-weighted imaging)
timeFrame: Baseline and 6 weeks post randomization
measure: Changes from pre- to post-treatment on peripheral Biomarkers assessed by structural MRI (Diffusion tensor imaging (DTI))
timeFrame: Baseline and 6 weeks post randomization
measure: Changes from pre- to post-treatment on peripheral Biomarkers assessed by functional MRI (resting state functional MRI scan)
timeFrame: Baseline and 6 weeks post randomization
measure: Changes from pre- to post-treatment on depressive symptoms using Beck's depression inventory
timeFrame: Baseline and 6 weeks post randomization
measure: Changes from pre- to post-treatment on Pittsburgh sleep quality index
timeFrame: Baseline and 6 weeks post randomization
measure: Changes from pre- to post-treatment on Neuropsychiatric symptoms (NPS) using MBI-C (Mild Behavioral Impairment Checklist)
timeFrame: Baseline and 6 weeks post randomization
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: St Michael's Hospital
state: Ontario
Study officials:
affiliation: Unity Health Toronto
name: Corinne Fischer, MD
role: PRINCIPAL_INVESTIGATOR
References: