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Trial record 81 of 158 for:    genetics AND Parkinson's disease

BEAM: Brain-Eye Amyloid Memory Study (BEAM)

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ClinicalTrials.gov Identifier: NCT02524405
Recruitment Status : Recruiting
First Posted : August 14, 2015
Last Update Posted : November 27, 2017
Sponsor:
Collaborators:
Brain Canada
Weston Brain Institute
GE Healthcare
University Health Network, Toronto
Centre for Addiction and Mental Health
Baycrest
St. Michael's Hospital, Toronto
Kensington Eye Institute
Information provided by (Responsible Party):
Dr. Sandra E Black, Sunnybrook Health Sciences Centre

Brief Summary:

The main objectives for this study are:

  1. To investigate novel, non-invasive ocular measurements including optical coherence tomography and eye tracking in a cross-sectional study of participants with various neurodegenerative dementias against standard cognitive assessments and brain imaging measures; and
  2. To assess the potential utility of ocular assessments for early detection in the pre-dementia, i.e. the so-called Mild Cognitive Impairment (MCI) stage, across the common neurodegenerative dementia syndromes and, Vascular Cognitive Impairment (VCI) due to small vessel disease (SVD).
  3. To determine the prevalence and relevance of amyloid uptake on PET scanning across the dementias most commonly associated with amyloidosis. Specifically we aim to examine correlations with amyloid uptake status in patients symptomatic from the most common proteinopathies (ie amyloid, tau, synuclein) combined in varying degrees with the most common vasculopathies (ie small vessel disease) using multimodal structural and functional imaging, cognitive behavioral, and gait and balance measures, taking into account genetic risk markers (particularly apolipoprotein E genotypes) and fluid biomarkers ( eg cytokines, oxidative stress, lipidomics).

Condition or disease Intervention/treatment
Alzheimer's Disease Mild Cognitive Impairment Vascular Cognitive Impairment Parkinson's Disease Lewy Body Disease Other: Flutemetamol PET scan

  Show Detailed Description

Study Type : Observational
Estimated Enrollment : 320 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: The Brain Eye Amyloid Memory (BEAM) Study: Validation of Ocular Measures as Potential Biomarkers for Early Detection of Brain Amyloid and Neurodegeneration
Study Start Date : February 2016
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : September 2019


Group/Cohort Intervention/treatment
Normal Controls
Sixty normal elders, 50-90 years old who are within normal limits on the study neuropsychological battery will be enrolled. All patients involved in the study will undergo SD-OCT, eye tracking, gait and balance assessments, blood draw for genomics and fluid biomarkers, neuropsychological assessment, brain MRI and brain amyloid PET.
Other: Flutemetamol PET scan
This is a cross-sectional study of patients with various forms of cognitive impairment and a healthy control group for comparison. Brain amyloid PET scans using the radioligand Flutemetamol, which is not yet approved for clinical use in Canada, will be performed in all subjects.

Alzheimer's Disease (AD)
Sixty-five subjects meeting the National Institute on Aging-Alzheimer's Association (NIA-AA) core clinical criteria for probable AD dementia will be enrolled. All patients will undergo SD-OCT, eye tracking, gait and balance assessments, blood draw for genomics and fluid biomarkers, neuropsychological assessment, brain MRI and brain amyloid PET. A subset will undergo SV-OCT.
Other: Flutemetamol PET scan
This is a cross-sectional study of patients with various forms of cognitive impairment and a healthy control group for comparison. Brain amyloid PET scans using the radioligand Flutemetamol, which is not yet approved for clinical use in Canada, will be performed in all subjects.

Mild Cognitive Impairment (VCI)
Sixty-five subjects meeting the National Institute on Aging-Alzheimer's Association criteria for amnestic or multi-domain MCI with MoCA score ≥18 will be enrolled. All patients will undergo SD-OCT, eye tracking, gait and balance assessments, blood draw for genomics and fluid biomarkers, neuropsychological assessment, brain MRI and brain amyloid PET. A subset will undergo SV-OCT.
Other: Flutemetamol PET scan
This is a cross-sectional study of patients with various forms of cognitive impairment and a healthy control group for comparison. Brain amyloid PET scans using the radioligand Flutemetamol, which is not yet approved for clinical use in Canada, will be performed in all subjects.

Subcortical Vascular Impairment (VCI)
Sixty-five subjects meeting the American Heart Association-American Stroke Association (AHA-ASA) criteria for probable vascular dementia (VaD) or probable vascular mild cognitive impairment (VaMCI) due to subcortical ischemic vascular disease , and probable or possible Cerebral Amyloid Angiopathy using the Modified Boston Criteria116 will be enrolled. All patients will undergo SD-OCT, eye tracking, gait and balance assessments, blood draw for genomics and fluid biomarkers, neuropsychological assessment, brain MRI and brain amyloid PET. A subset will undergo SV-OCT.
Other: Flutemetamol PET scan
This is a cross-sectional study of patients with various forms of cognitive impairment and a healthy control group for comparison. Brain amyloid PET scans using the radioligand Flutemetamol, which is not yet approved for clinical use in Canada, will be performed in all subjects.

LBD Spectrum
Sixty- five subjects with: Dementia with Lewy Bodies (DLB) meeting the criteria for probable Dementia with Lewy Bodies with MMSE score ≥20; or PD-MCI meeting the proposed Level I criteria for Mild Cognitive Impairment in Parkinson's Disease with MoCA score 18-24; or; PDD meeting the criteria for probable Parkinson's Disease - Dementia and MMSE score ≥20 will be enrolled. All patients involved will undergo SD-OCT, eye tracking, gait and balance assessments, blood draw for genomics and fluid biomarkers, neuropsychological assessment, brain MRI and brain amyloid PET. A subset will undergo SV-OCT.
Other: Flutemetamol PET scan
This is a cross-sectional study of patients with various forms of cognitive impairment and a healthy control group for comparison. Brain amyloid PET scans using the radioligand Flutemetamol, which is not yet approved for clinical use in Canada, will be performed in all subjects.




Primary Outcome Measures :
  1. Retinal nerve fiber layer thickness [ Time Frame: One-time assessment ]
    This potential ocular biomarker will compared among the different cohorts and be validated against brain MRI and brain amyloid PET.

  2. Amyloid Depostition [ Time Frame: One-time assessment ]
    This will be compared among the different cohorts and be validated against brain amyloid PET, and are expected to correlate meaningfully with cognitive and behavioural patterns, including retinal and eye-tracking, gait and balance.


Secondary Outcome Measures :
  1. Retinal artery narrowing [ Time Frame: One-time assessment ]
    The extent of correlation between retinal artery narrowing and the presence of covert lacunar infarcts on MRI will be assessed.

  2. Retinal venular widening [ Time Frame: One-time assessment ]
    The extent of correlation between retinal venular widening and the amount of periventricular white matter hyperintensities on MRI will be assessed.


Biospecimen Retention:   Samples With DNA
Blood samples for genetic testing including apoliprotein E4 status, as well as for proteomic, lipidomic and other fluid biomarkers of neurodegeneration and vascular disease, will be collected for each participant. All samples should be taken after a 10 hour fast; if not possible, the participant should have a light meal only. Samples should be collected between 8am and 10am, in order to minimize circadian variations in biomarker levels.


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Ages Eligible for Study:   50 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Three hundred and twenty (320) subjects will be enrolled: 60 normal elders (20 aged 50-64 and 40 aged 65-90), 65 with MCI, 65 with AD, 65 with LBD spectrum, and 65 with subcortical VCI.

All patients will receive a standardized work up for dementia including brain imaging and a blood work screen to rule out secondary causes of dementia as part of their clinical work-up prior to study enrollment. Memory clinic patients will undergo a detailed neurocognitive assessment (Toronto Cognitive Assessment - TorCA), and the clinical history and examination will use a standardized common elements approach.

Criteria

General Inclusion Criteria (All Subgroups)

Participants must meet each of the following criteria for enrolment into the study:

  1. Written informed consent obtained and documented
  2. Male or post-menopausal female (minimum of one year since the last menstrual period)
  3. 50-90 years of age
  4. Self-reported proficiency in speaking and understanding spoken English questions
  5. ≥8 years education
  6. Capable of cooperating for the duration of the study procedures and assessments
  7. Willing to undergo study procedures and remain unaware of the results (unless there are findings that are of clinical significance and would require further action, in the opinion of the study physician)
  8. Sufficient vision to participate in cognitive testing (corrected near visual acuity of Snellen 20/70 in at least one eye) and eye-tracking (able to identify symbols and stimuli presented on a computer screen in front of them)
  9. Sufficient corrected hearing to participate in cognitive testing
  10. Good venous access for phlebotomy to be performed
  11. Able to walk, with or without an assistive aid (e.g., cane, walker)

Subgroup-Specific Inclusion Criteria

Cognitively Normal Controls

  1. Cognitively normal and functionally independent in pre-screening history
  2. Within normal limits on the Behavioural Neurology Assessment-Revised (BNA-R)
  3. Within normal limits on the study neuropsychological battery

Mild Cognitive Impairment (MCI)

  1. Meets the National Institute on Aging-Alzheimer's Association criteria for single or multi-domain amnestic MCI111
  2. Impairment of episodic memory plus or minus other cognitive domains on the BNA-R
  3. Montreal Cognitive Assessment (MoCA) score ≥18
  4. Mini-Mental State Examination (MMSE) > 20
  5. In the opinion of the investigator if required: reliable and capable partner who has regular interaction with them, can provide a collateral history, can assist in compliance with study procedures, and who is willing to act as the Study Partner (provide written informed consent) and remain unaware of the results

Alzheimer's Disease (AD)

  1. Meets the National Institute on Aging-Alzheimer's Association (NIA-AA) core clinical criteria for probable or possible AD dementia112
  2. Mild early AD stage, as defined by MMSE score ≥18, Atypical cases with a MoCA ≥ 14 will also be allowed.
  3. Impairment in two or more cognitive domains on the BNA-R
  4. Reliable and capable partner who has regular interaction with them, can provide a collateral history, can assist in compliance with study procedures, and who is willing to act as the Study Partner (provide written informed consent) and remain unaware of the results

Lewy Body Disease (LBD) Spectrum PD-MCI

  1. Meets the proposed Level I criteria for Mild Cognitive Impairment in Parkinson's Disease 113
  2. MMSE score ≥20
  3. MoCA score ≥18
  4. Impairment in one or more cognitive domains
  5. Hoehn & Yahr stage 1-3
  6. Reliable and capable partner who has regular interaction with them, can provide a collateral history, can assist in compliance with study procedures, and who is willing to act as the Study Partner (provide written informed consent) and remain unaware of the results

LBD-MCI

  1. Meets the criteria for Dementia with Lewy Bodies (McKeith et al, 2017 in press)114 but has preserved daily functioning
  2. MMSE score ≥20
  3. MoCA score ≥18
  4. Impairment in one or more cognitive domains on the BNA-R
  5. Hoehn & Yahr stage ≤3
  6. Reliable and capable partner who has regular interaction with them, can provide a collateral history, can assist in compliance with study procedures, and who is willing to act as the Study Partner (provide written informed consent) and remain unaware of the results

Dementia with Lewy Bodies (DLB)

  1. Meets the criteria for probable or possible Dementia with Lewy Bodies (McKeith et al, 2017 in press)114
  2. MMSE score ≥14
  3. MoCA score ≤25
  4. Impairment in one or more cognitive domains on the BNA-R
  5. Reliable and capable partner who has regular interaction with them, can provide a collateral history, can assist in compliance with study procedures, and who is willing to act as the Study Partner (provide written informed consent) and remain unaware of the results

PDD

  1. Meets the criteria for probable Parkinson's Disease - Dementia115
  2. MMSE score ≥18
  3. MoCA score ≤25
  4. Impairment in two or more cognitive domains
  5. Hoehn & Yahr stage ≤4
  6. Reliable and capable partner who has regular interaction with them, can provide a collateral history, can assist in compliance with study procedures, and who is willing to act as the Study Partner (provide written informed consent) and remain unaware of the results

Subcortical Vascular Cognitive Impairment (VCI)

  1. Presence of subcortical vascular disease, indicated by the following:

    i. Periventricular Fazekas score = 3, with or without subcortical lacunes or small cortical infarcts (<1.5 cm in longest diameter); or ii. Fazekas score ≥ 2, with 2 or more subcortical lacunes or small cortical infarcts (<1.5 cm in longest diameter); or iii. Fazekas score = 0 or 1, with 3 subcortical lacunar infarcts (<1.5 cm in diameter), at least 1 in each hemisphere; or

    iv. Probable or possible Cerebral Amyloid Angiopathy using the Modified Boston Criteria116

  2. Impairment in one or more cognitive domains on the BNA-R
  3. Reliable and capable partner who has regular interaction with them, can provide a collateral history, can assist in compliance with study procedures, and who is willing to act as the Study Partner (provide written informed consent) and remain unaware of the results

Exclusion criteria General Exclusion Criteria (All Subgroups)

Participants who exhibit any of the following conditions will be excluded from the study:

  1. Underlying conditions (other than the disease being studied) which in the opinion of the investigator may interfere with the participant's ability to participate in the study or may compromise study results, including but not limited to:

    1. Unstable cardiac, pulmonary, renal, hepatic, endocrine (i.e. diabetes) or hematologic disease
    2. Active malignancy or infectious disease
    3. Significant psychiatric illness, including life-long depressive illness
    4. History of significant learning disability
    5. Significant other neurologic disease (e.g., multiple sclerosis, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma) or cognitive complications of cancer
    6. Symptomatic stroke within the past 6 months
    7. Substance abuse within the past year or history of alcohol or drug abuse which in the opinion of the investigator may interfere with the participant's ability to comply with the study procedures
    8. History of significant head trauma or recurrent concussions requiring hospitalization followed by persistent neurologic defaults or known structural brain abnormalities
    9. Pain or sleep disorder that could interfere with cognitive testing
    10. Any disability that would limit the ability to perform study assessments
  2. Ocular conditions, including:

    a. Clinical diagnosis of glaucoma, taking eye drops for glaucoma, or previous surgery (including laser) for glaucoma b. Any other serious eye disease or treatment or eye surgery, including any history of intra-vitreal injections c. History of optic neuritis d. Previous retinal laser therapy (either pan-retinal, or grid/focal) for diabetic retinopathy e. Cupping of the optic nerve head (ONH) consistent with a diagnosis of glaucoma, as clinically determined by expert ophthalmological assessment of digital colour fundus images centered on the ONH. Specifically, one or more of the following (assessed as part of SD-OCT visit at Kensington Eye Institute): i. a cup/disc ratio of 0.7 or greater in either eye ii. a cup/disc asymmetry of more than 0.2 iii. disc hemorrhage iv. notch f. Wet/exudative age-related macular degeneration (ARMD) in one or both eyes, as clinically determined by expert ophthalmological assessment of digital color fundus images centered on the fovea (assessed as part of SD-OCT visit at Kensington Eye Institute)

  3. Intra-ocular pressure greater than 22mmHg or a difference in intra-ocular pressure (Goldmann tonometry) greater than 5mmHg between the two eyes (assessed as part of SD-OCT visit at Kensington Eye Institute)
  4. Brain imaging abnormalities detected either on clinical MRI or CT prior to enrollment or on study MRI, including but not limited to:

    1. Evidence of infection
    2. Focal compressive mass lesions (tumours, subdural hematomas, malformations, etc.)
  5. Known hypersensitivity to Flutemetamol (18F) or any components of the Flutemetamol (18F) Injection formulation
  6. Contraindications to 3T MRI, as listed in the site-specific Magnetic Resonance Environment Screening Questionnaire (e.g. metal implant)
  7. Unable to tolerate the MRI environment (e.g., due to physical size and/or claustrophobia)
  8. Currently enrolled in a disease-modifying therapeutic trial that in the opinion of the Principal Investigator can potentially compromise study results

Subgroup-Specific Exclusion Criteria Cognitively Normal Controls

  1. Subjective memory complaints
  2. Brain imaging abnormalities detected either on clinical MRI or CT prior to enrollment or on study MRI, including but not limited to:

    1. Periventricular Fazekas score = 2.5 or 3
    2. Subcortical non-lacunar infarct or more than 1 subcortical lacunar infarct (<1.5 cm in longest diameter)
    3. Cortical ischemic stroke Cortical or subcortical hemorrhagic stroke >1.5cm in diameter

MCI, AD, and LBD Spectrum

(1) Brain imaging abnormalities detected either on clinical MRI or CT prior to enrollment or on study MRI, including but not limited to:

  1. Periventricular Fazekas score = 2.5 or 3
  2. Subcortical non-lacunar infarct or more than 1 subcortical lacunar infarct (<1.5 cm diameter)
  3. Cortical ischemic stroke >1.5cm in longest diameter
  4. Cortical or subcortical hemorrhagic stroke >1.5cm in diameter

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): NCT02524405


Contacts
Contact: Sandra E Black, MD sandra.black@sunnybrook.ca

Locations
Canada, Ontario
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: , BSc         
Principal Investigator: Sandra Black, MD         
St. Michael's Hospital Not yet recruiting
Toronto, Ontario, Canada, M5B 1W8
Principal Investigator: Corinne Fischer, MD         
University Health Network Not yet recruiting
Toronto, Ontario, Canada, M5T2S8
Principal Investigator: Carmela Tartaglia, MD, FRCPC         
Baycrest Health Sciences Not yet recruiting
Toronto, Ontario, Canada, M6A 2E1
Contact: Brad Pugh    406.785.2500 ext 6207    b.pugh@baycrest.org   
Principal Investigator: Morris Freedman, MD         
Centre for Addiction and Mental Health (CAMH) Not yet recruiting
Toronto, Ontario, Canada
Contact: Shirley Yiu    416-535-8501 ext 33091    Shirley.Yui@camh.ca   
Contact: Lina Chiuccariello    416-535-8501 ext 30409    Lina.Chiuccariello@camh.ca   
Principal Investigator: Sanjeev Kumar, MD         
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Brain Canada
Weston Brain Institute
GE Healthcare
University Health Network, Toronto
Centre for Addiction and Mental Health
Baycrest
St. Michael's Hospital, Toronto
Kensington Eye Institute
Investigators
Principal Investigator: Sandra Black, MD Sunnybrook Health Sciences Center

Responsible Party: Dr. Sandra E Black, Principal Investigator, Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT02524405     History of Changes
Other Study ID Numbers: 221-2013
First Posted: August 14, 2015    Key Record Dates
Last Update Posted: November 27, 2017
Last Verified: November 2017

Additional relevant MeSH terms:
Parkinson Disease
Alzheimer Disease
Lewy Body Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Cognitive Dysfunction
Dementia
Tauopathies