Clinical trial NCT05107882: Optina Diagnostics' Cerebral ß-Amyloid Status (CAS) Test
Official title: Retinal Deep PhenotypingTM Platform for Cerebral Amyloid Status Evaluation: a Validation Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alzheimer Disease
Mild Cognitive Impairment
Mild Dementia
Lead sponsor: Optina Diagnostics Inc.
Sponsor class: INDUSTRY
Collaborators: name: Eastern Virginia Medical School
name: The Cleveland Clinic
name: University of Washington
name: Sunnybrook Research Institute
First posted: 2021-11-04
Enrollment: 466
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: The target population for the Optina Diagnostics' CAS test is men and women 50 years and older who are under clinical investigation for cognitive impairment where Alzheimer's disease (AD) is one of the possible differential diagnoses.

As concomitant eye pathologies or conditions could interfere with CAS algorithm, individuals with certain ocular pathologies or conditions, including glaucoma, age-related macular degeneration (AMD), retinopathies, and advanced cataracts, will not be included in the target population at this time. Work is on-going to improve the CAS classifier algorithm with the goal to include these individuals in the target population at a later date.

Brief summary: This observational, cross-sectional study is designed to validate a novel diagnostic test for the detection of phenotypic changes in the retina that correlate with likely PET amyloid status (negative or positive), to aid in the evaluation of adult patients with cognitive impairment who are being evaluated for Alzheimer's disease and other causes of cognitive decline. The CAS test is an adjunct to other diagnostic evaluations, and is indicated for use with the Optina Diagnostics' MHRC (K200254).

Detailed description: This non-interventional, cross-sectional study is designed to validate a novel diagnostic test, the Optina Diagnostics' Cerebral ß-Amyloid Status (CAS) test, for the detection of phenotypic changes in the retina that correlate with likely PET amyloid status (positive or negative). The CAS test is an adjunct to other diagnostic evaluations, and is indicated for use with the Optina Diagnostics' MHRC for imaging the retina. The study objective is to characterize the performance of the diagnostic CAS test in the target population of adult patients fifty (50) years and older with cognitive impairment, who are being evaluated for Alzheimer's disease (AD) and other causes of cognitive decline. The data generated in this study will provide evidence to be used in the assessment of the benefits and risks associated with use of the device in the intended population. The primary endpoint is to demonstrate accuracy of the Optina Diagnostics' CAS test compared to amyloid-PET status, as determined by a majority of three (3) qualified, independent PET Readers.

Eligibility criteria: Inclusion Criteria:

* Male and female adults aged 50 years and older (inclusive).
* Individuals with reported cognitive complaint (self or from an informant) under clinical investigation by a health professional for cognitive impairment where Alzheimer's disease (AD) is one of the differential diagnoses.
* Demonstrated cognitive impairment as evidenced by at least one of the following:

  1. Mini Mental State Examination (MMSE) score \< 26/30
  2. Montreal Cognitive Assessment (MoCA) score \< 26/30
  3. Score \> 1 Standard Deviation below population mean on a standardized neuropsychological test (in any domain), based on normative data from age-, sex-, education-, and where possible, race-matched peers \[Based on guidelines for detecting Mild Cognitive Impairment due to AD (Albert et al., 2011)\]
* Clinical laboratory assessment (complete blood count \[CBC\], standard blood chemistry profile, thyroid stimulating hormone \[TSH\], vitamin B12) within the 6 months prior to enrollment.
* Cognitive impairment on the above test/s is unable to be fully explained by systemic, neurological or psychiatric disorders other than Alzheimer's disease.
* Capacity to give informed consent by patient or substitute decision maker.
* Ability to undergo PET and MRI scans.

Exclusion Criteria:

* Any ophthalmologic condition that would prevent obtaining retinal imaging and/or could interfere with the analysis of the MHRC images by the CAS, including:

  1. Pupil dilation contraindicated (due to a pathology, or presence of 3 quadrants with Van Herick grading of 0 or 1 without iridotomy)
  2. Inadequate pupil dilatation (\< 6mm diameter) preventing uniform illumination of the retina with the MHRC
  3. Diagnosis of glaucoma or signs of glaucoma (excavation ratio ≥0.7)
  4. Signs of vascular occlusion or retinopathy (microaneurysm, exudate, hemorrhage or edema) within a diameter of 10 mm from the mid-point between the optic nerve head and the macula
  5. Presence of drusen and/or age-related macular degeneration (AREDS 9-step scale ≥4 - cumulative drusen area diameter ≥ 250 um, pigmentary changes and cumulative drusen area diameter ≥ 63 um or pigmentary changes and cumulative geographic atrophy area diameter ≥ 354 um)
  6. Macular anomaly (e.g., macular hole, dystrophy, degeneration)
  7. Nuclear sclerosis \> 2 (LOCS II four-point grading system) or presence of central cortical or central posterior subcapsular cataract
  8. Refractive error outside the range of -15 D to +15 D
  9. Scar, atrophy, naevus, tumor, eepiretinal membrane or retinal pucker with a cumulative area \> 1 disc area within a diameter of 10 mm from the mid-point between the optic nerve head and the macula
  10. Papilledema
  11. Deficient visual fixation (inability to fixate for at least 2 s)
  12. Corneal or media opacities (e.g., Weiss ring) affecting retinal imaging on a cumulative area \> 1 disc area within a diameter of 10 mm from the mid-point between the optic nerve head and the macula (i.e., the area of interest for the MHRC imaging)
* Inability of obtaining at least 3 images of satisfactory quality with the MHRC per the Optina Diagnostics quality index software and /or per the eye specialists' evaluation.
* Impossibility of obtaining a satisfactory quality amyloid-PET scan for interpretation by imaging specialists.
* Individuals who currently or have previously taken cerebral amyloid modifying medication.

Primary outcomes:
measure: Retinal beta-amyloid detection
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: Ezy Medical Research
state: Florida
city: Las Vegas
country: United States
facility: Lou Ruvo Center for Brain Health at Cleveland Clinic (LR-CC)
state: Nevada
city: Norfolk
country: United States
facility: East Virginia Medical School (EVMS)
state: Virginia
city: Seattle
country: United States
facility: University of Washington (MBWC)
state: Washington
city: Ottawa
country: Canada
facility: Ottawa Memory Clinic (OMC)
state: Ontario
city: Toronto
country: Canada
facility: Centricity Research
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Eastern Virginia Medical Center
name: Hamid Okhravi, MD, PhD FRPC
role: PRINCIPAL_INVESTIGATOR
affiliation: Ottawa Memory Clinic and Clinic Memoire Outaouais
name: Richard Bergeron, PhD FRPC
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: Suman Jayadev, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cleveland Clinic Lou Ruvo Center for Brain
name: Charles Bernick, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Research Institute (SRI)
name: Sandra Black, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ezy Medical Research
name: Jorge P. Bruno, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centricity Research
name: Giovanni J Marotta, MD, FRCP(C)
role: PRINCIPAL_INVESTIGATOR
References: