Neuro RX Gamma for Amnestic Mild Cognitive Impairment (aMCI)
Primary Purpose
MCI, Amnestic Mild Cognitive Disorder
Status
Recruiting
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Neuro RX Gamma device
Sham Neuro RX Gamma device
Sponsored by
About this trial
This is an interventional treatment trial for MCI focused on measuring MCI, Photobiomodulation, PBM, AD
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.
- Adequate caregiver to ensure compliance of home-based treatments and to complete study assessments and questionnaires.
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.
Sites / Locations
- St Michael's HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Sham Comparator
Arm Label
Active Neuro Rx Device
Sham Neuro Rx Device
Arm Description
The active device will deliver light for the 20 minutes session duration.
The Sham device is indistinguishable from the active device. The sham device will not deliver light for the 20 minutes session duration.
Outcomes
Primary Outcome Measures
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
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
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
Changes from pre- to post-treatment on processing speed assessed by Trail Making Test (TMT)-part A
Trail Making A - Time per correct connection
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
Secondary Outcome Measures
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.
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.
Changes from pre- to post-treatment on peripheral Biomarkers assessed by structural MRI (T1-weighted imaging)
Cortical thickness and subcortical volume
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
Changes from pre- to post-treatment on peripheral Biomarkers assessed by functional MRI (resting state functional MRI scan)
Brain networks functional connectivity
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.
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
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
Full Information
NCT ID
NCT05563298
First Posted
September 16, 2022
Last Updated
February 14, 2023
Sponsor
Unity Health Toronto
1. Study Identification
Unique Protocol Identification Number
NCT05563298
Brief Title
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
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 14, 2023 (Anticipated)
Primary Completion Date
October 30, 2023 (Anticipated)
Study Completion Date
December 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Unity Health Toronto
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MCI, Amnestic Mild Cognitive Disorder
Keywords
MCI, Photobiomodulation, PBM, AD
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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
Participant
Masking 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.
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Active Neuro Rx Device
Arm Type
Active Comparator
Arm Description
The active device will deliver light for the 20 minutes session duration.
Arm Title
Sham Neuro Rx Device
Arm Type
Sham Comparator
Arm Description
The Sham device is indistinguishable from the active device. The sham device will not deliver light for the 20 minutes session duration.
Intervention Type
Device
Intervention Name(s)
Neuro RX Gamma device
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Sham Neuro RX Gamma device
Intervention Description
The Sham device is indistinguishable from the active device. The sham device will not deliver light for the 20 minutes session duration.
Primary Outcome Measure Information:
Title
Changes from pre- to post-treatment on mental status and cognitive function assessed by Mini-Mental State Examination (MMSE)
Description
MMSE is a brief 30-point assessment
Time Frame
Baseline and 6 weeks post randomization
Title
Changes from pre- to post-treatment on verbal learning and memory assessed by California Verbal Learning Test II (CVLTII)
Description
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
Time Frame
Baseline and 6 weeks post randomization
Title
Changes from pre- to post-treatment on visuospatial memory assessed by Brief Visuospatial Memory Test Revised (BVMT-R)
Description
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
Time Frame
Baseline and 6 weeks post randomization
Title
Changes from pre- to post-treatment on processing speed assessed by Trail Making Test (TMT)-part A
Description
Trail Making A - Time per correct connection
Time Frame
Baseline and 6 weeks post randomization
Title
Changes from pre- to post-treatment on executive functioning assessed by Trail Making Test (TMT)-B/A and Stroop Color and Word Test (SCWT)
Description
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
Time Frame
Baseline and 6 weeks post randomization
Secondary Outcome Measure Information:
Title
Changes from pre- to post-treatment on Quality of life using QOL-AD
Description
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.
Time Frame
Baseline and 6 weeks post randomization
Title
Changes from pre- to post-treatment on peripheral Biomarkers assessed by blood
Description
Blood lactate and lactate/pyruvate ratio will be measured due to their noted relationship with mitochondrial function.
Time Frame
Baseline and 6 weeks post randomization
Title
Changes from pre- to post-treatment on peripheral Biomarkers assessed by structural MRI (T1-weighted imaging)
Description
Cortical thickness and subcortical volume
Time Frame
Baseline and 6 weeks post randomization
Title
Changes from pre- to post-treatment on peripheral Biomarkers assessed by structural MRI (Diffusion tensor imaging (DTI))
Description
fractional anisotropy (FA), and mean diffusivity (MD) measure
Time Frame
Baseline and 6 weeks post randomization
Title
Changes from pre- to post-treatment on peripheral Biomarkers assessed by functional MRI (resting state functional MRI scan)
Description
Brain networks functional connectivity
Time Frame
Baseline and 6 weeks post randomization
Title
Changes from pre- to post-treatment on depressive symptoms using Beck's depression inventory
Description
Beck's depression inventory is a 21-item multiple-choice self-report inventory rating inventory that measures characteristic attitudes and symptoms of depression.
Time Frame
Baseline and 6 weeks post randomization
Title
Changes from pre- to post-treatment on Pittsburgh sleep quality index
Description
The measure consists of 19 individual items, creating 7 components that produce one global score
Time Frame
Baseline and 6 weeks post randomization
Title
Changes from pre- to post-treatment on Neuropsychiatric symptoms (NPS) using MBI-C (Mild Behavioral Impairment Checklist)
Description
The MBI-C is a 34-item instrument and serves as a global and domain-specific NPS measure including early symptom presentations
Time Frame
Baseline and 6 weeks post randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
95 Years
Accepts Healthy Volunteers
No
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.
Adequate caregiver to ensure compliance of home-based treatments and to complete study assessments and questionnaires.
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Corinne Fischer, MD
Phone
416-864-5320
Email
Corinne.Fischer@unityhealth.to
First Name & Middle Initial & Last Name or Official Title & Degree
Arthishia Art Shanmuganathan
Phone
647-227-8986
Email
Arthishia.Shanmuganathan@unityhealth.to
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Corinne Fischer, MD
Organizational Affiliation
Unity Health Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arthishia Shanmuganathan
Phone
647-227-8986
Email
Arthishia.Shanmuganathan@unityhealth.to
First Name & Middle Initial & Last Name & Degree
Adrienne Atayde
Email
adrienne.atayde@unityhealth.to
First Name & Middle Initial & Last Name & Degree
Corinne Fischer, MD
12. IPD Sharing Statement
Plan to Share IPD
No
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Neuro RX Gamma for Amnestic Mild Cognitive Impairment (aMCI)
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