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Multimodal Ocular Imaging in Neurodegeneration

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03699644
Recruitment Status : Recruiting
First Posted : October 9, 2018
Last Update Posted : May 29, 2019
Sponsor:
Information provided by (Responsible Party):
Cagri Besirli, University of Michigan

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Alzheimer Dementia Frontotemporal Dementia Device: Spectral-Domain Optical Coherence Tomography (SD-OCT) Device: Magnetic Resonance Imaging (MRI) Device: Positron Emission Tomography (PET) Diagnostic Test: Comprehensive Ophthalmic Examination Device: Fundus Photography Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Multimodal Ocular Imaging in Neurodegeneration
Actual Study Start Date : January 4, 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Active Comparator: 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 Name: 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 Name: 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 Name: Photography of the Eye

Active Comparator: 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 Name: 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 Name: 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 Name: Photography of the Eye

Active Comparator: 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 Name: 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 Name: 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 Name: Photography of the Eye




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Presence of Amyloid Plaque [ Time Frame: 45 Minutes ]
    Fundus autofluorescence (FAF) will be used to detect the presence of lipofuscin

  2. 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.

  3. 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.

  4. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   45 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03699644


Contacts
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Contact: Cagri G. Besirli, MD PhD (734) 615 - 2479 cbesirli@med.umich.edu
Contact: Omar Moinuddin, MD (847) 217 - 5387 omoinudd@med.umich.edu

Locations
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United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Cagri G. Besirli, MD PhD    734-615-2479    cbesirli@med.umich.edu   
Sponsors and Collaborators
University of Michigan
Investigators
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Principal Investigator: Cagri G. Besirli, MD PhD University of Michigan

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Responsible Party: Cagri Besirli, Assistant Professor of Ophthalmology, University of Michigan
ClinicalTrials.gov Identifier: NCT03699644    
Other Study ID Numbers: HUM00146956
First Posted: October 9, 2018    Key Record Dates
Last Update Posted: May 29, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Cagri Besirli, University of Michigan:
FTD
Dementia
Retina
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain
Nerve Degeneration
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Frontotemporal Lobar Degeneration
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Pathologic Processes