Clinical trial NCT05604183: Hyperspectral Retinal Observations for the Cross-sectional Detection of Alzheimer's Disease
Official title: Hyperspectral Retinal Observations for the Cross-sectional Detection of Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Alzheimer Disease, Early Onset
Cognitive Impairment
Cognitive Decline
Keywords: Retinoscopy
Non-invasive
Accessible healthcare
Lead sponsor: Mantis Photonics AB
Sponsor class: INDUSTRY
Collaborators: name: Blekinge Institute of Technology
name: Blekinge County Council Hospital
First posted: 2022-11-03
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Two devices will be tested in this research:

1. Mantis Photonics' hyperspectral camera for non-invasive retinal examination (i.e., a hardware medical device under investigation).
2. Blekinge CoGNIT cognitive ability test (i.e., an assessment).

Detailed description: Worldwide, millions of people are affected by neurodegenerative diseases (e.g., Alzheimer's disease, dementia). Those diseases are having a tremendous socio-economic impact on our society. The cost associated with treating and caring for those diseases is enormous. Overwhelming evidence indicates how selective lifestyle changes (e.g., reducing exposure to known risk factors) can sometimes significantly decrease the probability of developing the disease or delay its onset. However, the diseases must be diagnosed early for them to be effective. There is a lack of accessible, inexpensive, and non-invasive practices that would allow for an early diagnosis of different diseases, even at the primary physician's office. Mantis Photonics and Blekinge Tekniska Högskola (Institustionen för Hälsa) aim to fill this urgent unmet medical need.

Strong indications of the possibility of classifying Alzheimer's status based on hyperspectral scans of the retina have been published by different researchers. These results were obtained based on images taken with hyperspectral cameras with a different working principle than the Mantis Photonics camera. The working principle of the Mantis Photonics camera allows making a hyperspectral retinoscopy with the same spectral range and comparable or better spectral resolution with a machine that is more modular and lower in cost. There is thus reason to hypothesize retinal scans taken with the Mantis Photonics camera can be used for the same classification task.

Previous studies on the automated tablet computer cognitive test CoGNIT have established validity, reliability and sensitivity for testing patients with Normal Pressure Hydrocephalus (NPH) . Recently feasibility of testing in Mild Cognitive Impairment (MCI) was affirmed (Behrens, Berglund, \& Anderberg, CoGNIT Automated Tablet Computer Cognitive Testing in Patients With Mild Cognitive Impairment: Feasibility Study, 2022). In NPH patients, CoGNIT was more sensitive to cognitive impairment at baseline and cognitive improvement after shunt surgery than the Mini-Mental State Examination (MMSE).

Blood tests for amyloid-β and other biomarkers related to Alzheimer's disease are being investigated for clinical practice, but the technique is not accepted as a standard test. Research has shown that renal function influences amyloid-β clearance from the body. Also, analytical errors influence test results. Therefore, one can question the influence of normal repeatability of the blood test result.

The aim of this investigation is the evaluation, (further) development and comparison of non-invasive techniques for the evaluation of patients suffering mild cognitive impairment, in particular, the Mantis Photonics hyperspectral camera with classification machine learning model in combination with the CoGNIT test of Dr Behrens (Blekinge Tekniska Högskola). These techniques will be compared to the result of cerebrospinal fluid analysis (CSF), the reference biological diagnostic technique for Alzheimer's disease.

Eligibility criteria: Inclusion Criteria:

* subject age over 18 years old
* The subject has undergone a lumbar puncture an cerebrospinal fluid analysis as part of the standard care.
* The subject has at least one healthy eye.
* The subject is applicable for taking a blood sample for the blood analysis test.
* The informed consent is provided, explained and understood by the person. The person has consented to the informed consent.

Exclusion Criteria:

* There are contra-indications for lumbar puncture (eg: brain tumor with suspicion of raised intracranial pressure, coagulopathies or ongoing anticoagulant medications) will be excluded from the study.
* When the subject suffers from excessive visual or auditive impairment, the he/she will be excluded from the CoGNIT track.

Primary outcomes:
measure: Accuracy (Statistical metric) retinal image classification model
timeFrame: within 2 months after last patient procedure
measure: Area under the Curve (statistical metrics) retinal image classification model
timeFrame: within 2 months after last patient procedure
measure: Sensitivity (Statistical metric) retinal image classification model
timeFrame: within 2 months after last patient procedure
measure: CoGNIT test diagnostic accuracy
timeFrame: within 2 months after last patient procedure
Secondary outcomes:
measure: Accuracy: Metrics combination model
timeFrame: within 3 months after last patient procedure
measure: Area Under the Curve: Metrics combination model
timeFrame: within 3 months after last patient procedure
measure: Sensitivity: Metrics combination model
timeFrame: within 3 months after last patient procedure
measure: Non invasive test variability compared to reference
timeFrame: within 3 months after last patient procedure
Other outcomes:
measure: Adverse effect
timeFrame: Immediately after the retinoscopy procedure
measure: Serious adverse effect
timeFrame: Immediately after the retinoscopy procedure
Locations:
city: Karlskrona
country: Sweden
facility: Blekinge Tekniska Högskola
state: Blekine Län
city: Karlskrona
country: Sweden
facility: Blekinge Hospital
state: Blekinge Län
Study officials:
affiliation: Blekinge Tekniska Högskola
name: Anders Behrens, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Behrens A, Berglund JS, Anderberg P. CoGNIT Automated Tablet Computer Cognitive Testing in Patients With Mild Cognitive Impairment: Feasibility Study. JMIR Form Res. 2022 Mar 11;6(3):e23589. doi: 10.2196/23589.
citation: Behrens A, Eklund A, Elgh E, Smith C, Williams MA, Malm J. A computerized neuropsychological test battery designed for idiopathic normal pressure hydrocephalus. Fluids Barriers CNS. 2014 Sep 25;11:22. doi: 10.1186/2045-8118-11-22. eCollection 2014.
citation: Behrens A, Elgh E, Leijon G, Kristensen B, Eklund A, Malm J. The Computerized General Neuropsychological INPH Test revealed improvement in idiopathic normal pressure hydrocephalus after shunt surgery. J Neurosurg. 2019 Feb 8;132(3):733-740. doi: 10.3171/2018.10.JNS18701. Print 2020 Mar 1.
citation: Budelier MM, Bateman RJ. Biomarkers of Alzheimer Disease. J Appl Lab Med. 2020 Jan 1;5(1):194-208. doi: 10.1373/jalm.2019.030080.
citation: Hadoux X, Hui F, Lim JKH, Masters CL, Pebay A, Chevalier S, Ha J, Loi S, Fowler CJ, Rowe C, Villemagne VL, Taylor EN, Fluke C, Soucy JP, Lesage F, Sylvestre JP, Rosa-Neto P, Mathotaarachchi S, Gauthier S, Nasreddine ZS, Arbour JD, Rheaume MA, Beaulieu S, Dirani M, Nguyen CTO, Bui BV, Williamson R, Crowston JG, van Wijngaarden P. Non-invasive in vivo hyperspectral imaging of the retina for potential biomarker use in Alzheimer's disease. Nat Commun. 2019 Sep 17;10(1):4227. doi: 10.1038/s41467-019-12242-1.
citation: Rasmussen J, Langerman H. Alzheimer's Disease - Why We Need Early Diagnosis. Degener Neurol Neuromuscul Dis. 2019 Dec 24;9:123-130. doi: 10.2147/DNND.S228939. eCollection 2019.
citation: Teunissen CE, Verberk IMW, Thijssen EH, Vermunt L, Hansson O, Zetterberg H, van der Flier WM, Mielke MM, Del Campo M. Blood-based biomarkers for Alzheimer's disease: towards clinical implementation. Lancet Neurol. 2022 Jan;21(1):66-77. doi: 10.1016/S1474-4422(21)00361-6. Epub 2021 Nov 24.