Multimodal Ocular Imaging in Neurodegeneration

March 10, 2022 updated by: Cagri Besirli, University of Michigan
Alzheimer's disease (AD) and frontotemporal dementia (FTD) are two of the most common types of age-related neurodegenerative disorders. Identifying at-risk patients and gauging disease progression in a non-invasive manner would be invaluable. Early and correct diagnosis is crucial for coordinating supportive care, patient expectations, caregiver arrangements and family planning. In addition, as treatments become available, beginning therapy early in the disease before symptoms become severe will be important. Multimodal ocular imaging (MOI) includes an ophthalmic (eye) exam and eye photographs to evaluate different layers of the retina, which is the light sensing layer of the eye. Newer technologies make it possible to visualize the disease process occurring in AD and FTD by using MOI to look at the retina, since the retina is fundamentally an outward extension of the brain itself. This study will attempt to correlate signs of disease in the retina, as determined by MOI, with plaque buildup in the brain as seen by imaging. This will demonstrate the sensitivity and specificity of MOI for diagnosing AD and FTD in a noninvasive manner.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

41 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients are recruited with mid-to-late stage AD and FTD, as well as age-matched healthy controls, using the extensive database of research participants maintained by the Michigan Alzheimer's Disease Center (MADC).

Description

Inclusion Criteria:

  • Subjects with dementia must have known diagnosis of Alzheimer's dementia (AD) or frontotemporal dementia (FTD)
  • Subjects with dementia must have Moderate/severe dementia as preferentially defined by a documented MoCA score of less than 17, or by MMSE score of less than 17, within the last 12 months
  • Individuals with no evidence of AD or FTD as age-matched controls.

Exclusion Criteria:

  • Preexisting retinal or optic nerve disorder including macular degeneration, diabetic retinopathy, retinal dystrophy, and glaucoma
  • Anterior segment abnormalities of the eye limiting ocular imaging (e.g. corneal disorders, dense cataract).
  • Use of medications with known effects on the retina or optic nerve (e.g. hydroxychloroquine, ethambutol).
  • Pregnant or lactating women.
  • Prisoners.
  • Subjects with advanced dementia who cannot be independently and reliably positioned at the ocular imaging device for reliable imaging.
  • Subjects with contraindications to magnetic resonance (MR) imaging, including pacemakers or claustrophobia.
  • Evidence of large vessel stroke or mass lesion identified on MR imaging.
  • Subjects limited by participation in research procedures involving ionizing radiation.
  • Subjects who are already participating in another clinical study or clinical trial
  • Participants with a clinically significant or unstable medical or surgical condition that, in the opinion of any of the investigators, might preclude safe completion of the study or might affect the results of the study. These include conditions causing significant central nervous system or autonomic dysfunction, such as congestive heart failure, recent (<6 months) myocardial infarction, thrombocytopenia (<50 x 10(9)/L), immunosuppressed state, severe uncontrolled hypertension, severe cardiopulmonary disease, severe anemia (hemoglobin <8g/dl), severe liver or kidney disease (creatinine >2.3 mg/dl) uncontrolled diabetes mellitus (HgbA1c >10g%), alcoholism, malignant neoplasms, amyloidosis, uncontrolled hypothyroidism, unstable peripheral neuropathies, concurrent infections, orthopedic problems that compromise mobility and activities of daily living, severe cerebrovascular accidents (causing symptoms such as hemiplegia, aphasia and non-dominant parietal lobe syndrome), history of exposure to neurotoxins or neuroactive drugs, or parkinsonism due to drugs (including neuroleptics, alpha-methyldopa, reserpine, metoclopramide).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Healthy Control
Healthy controls will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, all healthy controls will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Device: Spectral-Domain Optical Coherence Tomography (SD-OCT)
Each participant in this study will undergo Optical coherence tomography (OCT), a non-invasive imaging test of the eye, one time. OCT uses light waves to take cross-section pictures of the retina, which are generated using scattered light waves.
Other Names:
  • Imaging of the Eye
Device: Magnetic Resonance Imaging (MRI)
Each participant in this study will undergo a single Magnetic resonance imaging (MRI) scan, a scanning technique for creating detailed images of the human body. The scan uses a magnetic field and radio waves to generate images of the brain.
Device: Positron Emission Tomography (PET)
Each participant in this study will undergo a single Positron emission tomography (PET) scan of the brain. PET is a nuclear medicine functional imaging technique that is used to observe metabolic processes in the brain as an aid to the diagnosis of disease using the combination of a radioactive tracer, camera, and a computer.
Diagnostic test: Comprehensive Ophthalmic Examination
Each participant in this study will receive one comprehensive eye examination which will be performed by a licensed ophthalmologist at the University of Michigan. This examination will include the assessment of the participant's visual acuity, a slit lamp examination which will look at the anterior and posterior tissues of the eye including the retina using various lights and lenses, and intraocular pressures.
Other Names:
  • Comprehensive Eye Examination
Device: Fundus Photography
Each participant in this study will undergo fundus photography of each eye. Fundus photography involves the use of a retinal camera coupled with a low power microscope to capture photographs of the retina.
Other Names:
  • Photography of the Eye
Alzheimer's Dementia
Subjects with Alzheimer's Dementia will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, all subjects with Alzheimer's Dementia will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Device: Spectral-Domain Optical Coherence Tomography (SD-OCT)
Each participant in this study will undergo Optical coherence tomography (OCT), a non-invasive imaging test of the eye, one time. OCT uses light waves to take cross-section pictures of the retina, which are generated using scattered light waves.
Other Names:
  • Imaging of the Eye
Device: Magnetic Resonance Imaging (MRI)
Each participant in this study will undergo a single Magnetic resonance imaging (MRI) scan, a scanning technique for creating detailed images of the human body. The scan uses a magnetic field and radio waves to generate images of the brain.
Device: Positron Emission Tomography (PET)
Each participant in this study will undergo a single Positron emission tomography (PET) scan of the brain. PET is a nuclear medicine functional imaging technique that is used to observe metabolic processes in the brain as an aid to the diagnosis of disease using the combination of a radioactive tracer, camera, and a computer.
Diagnostic test: Comprehensive Ophthalmic Examination
Each participant in this study will receive one comprehensive eye examination which will be performed by a licensed ophthalmologist at the University of Michigan. This examination will include the assessment of the participant's visual acuity, a slit lamp examination which will look at the anterior and posterior tissues of the eye including the retina using various lights and lenses, and intraocular pressures.
Other Names:
  • Comprehensive Eye Examination
Device: Fundus Photography
Each participant in this study will undergo fundus photography of each eye. Fundus photography involves the use of a retinal camera coupled with a low power microscope to capture photographs of the retina.
Other Names:
  • Photography of the Eye
Frontotemporal Dementia
Subjects with Frontotemporal Dementia will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, subjects with Frontotemporal Dementia will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Device: Spectral-Domain Optical Coherence Tomography (SD-OCT)
Each participant in this study will undergo Optical coherence tomography (OCT), a non-invasive imaging test of the eye, one time. OCT uses light waves to take cross-section pictures of the retina, which are generated using scattered light waves.
Other Names:
  • Imaging of the Eye
Device: Magnetic Resonance Imaging (MRI)
Each participant in this study will undergo a single Magnetic resonance imaging (MRI) scan, a scanning technique for creating detailed images of the human body. The scan uses a magnetic field and radio waves to generate images of the brain.
Device: Positron Emission Tomography (PET)
Each participant in this study will undergo a single Positron emission tomography (PET) scan of the brain. PET is a nuclear medicine functional imaging technique that is used to observe metabolic processes in the brain as an aid to the diagnosis of disease using the combination of a radioactive tracer, camera, and a computer.
Diagnostic test: Comprehensive Ophthalmic Examination
Each participant in this study will receive one comprehensive eye examination which will be performed by a licensed ophthalmologist at the University of Michigan. This examination will include the assessment of the participant's visual acuity, a slit lamp examination which will look at the anterior and posterior tissues of the eye including the retina using various lights and lenses, and intraocular pressures.
Other Names:
  • Comprehensive Eye Examination
Device: Fundus Photography
Each participant in this study will undergo fundus photography of each eye. Fundus photography involves the use of a retinal camera coupled with a low power microscope to capture photographs of the retina.
Other Names:
  • Photography of the Eye

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Presence of Retinal Thinning
Time Frame: 45 minutes
Imaging of the eye will be used to measure differences in retinal thickness between subjects with Alzheimer's Dementia, Frontotemporal Dementia, and healthy age-matched controls.
45 minutes

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Presence of Amyloid Plaque
Time Frame: 45 Minutes
Fundus autofluorescence (FAF) will be used to detect the presence of lipofuscin
45 Minutes
Presence of Brain Pathology
Time Frame: 60 Minutes
MRI of the brain will be performed in order to determine if pathology observed on neuroimaging correlates quantitatively and/or qualitatively with retinal thickness.
60 Minutes
Presence of Brain Metabolism
Time Frame: 180 Minutes
PET scanning of the brain will be performed in order to determine if brain metabolism observed on neuroimaging correlates quantitatively and/or qualitatively with retinal thickness.
180 Minutes
Presence of Macular Vascular Anomalies
Time Frame: 45 Minutes
Imaging of the eye will be used to measure differences in vascular density between subjects with Alzheimer's Dementia, Frontotemporal Dementia, and healthy age-matched controls.
45 Minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Michigan

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Cagri G. Besirli, MD PhD, University of Michigan

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 4, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 3, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 3, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 5, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 5, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 9, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 28, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HUM00146956

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

IPD Data may be shared if requests to the PI are made, a reasonable plan is proposed, and Data Use agreements are put in place.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings