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Alzheimer's DiseaseMITNEC C6NCT02330510

Amyloid and Glucose PET Imaging in Alzheimer and Vascular Cognitive Impairment Patients With Significant White Matter Disease

An observational study of Alzheimer's Disease and Small Vessel Disease White Matter Hyperintensities Subtype, run by Dr. Sandra E Black at 8 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The prevalence of both Alzheimer's Disease (AD) and stroke doubles each decade over 65 years old. Both are major causes of dementia, currently estimated to affect 46 million people worldwide. The current costs globally are $818 billion. Read more about this study

Who is it for?
Ages 60 years and older
How many people
80 participants
Where
8 sitesCanada
Study dates
Aug 2014to 10 Dec 2024
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Two groups of patients will participate in this study: 1. Patients with early Alzheimer's Disease (AD) or amnestic or multi-domain Mild Cognitive Impairment who have extensive pvWMH; recruited from memory clinics (n= 40) 2. Patients who have had a stroke or a Transient Ischemic Attack (TIA) with extensive pvWMH; recruited from stroke prevention clinics (n= 40)

Who may be able to join

None listed.

Who cannot join

  • Subject meeting any one of the following criteria are not eligible for the the study:
  • Patients with cortical or non-lacunar infarct on imaging
  • Patients with persisting hemiparesis after a motor stroke, leg strength <4/5 on the Medical Research Council (MRC) scale; significant cerebellar ataxia
  • Patients with contraindications to 3T MRI
  • Patients with major psychiatric disorder during the preceding 5 years
  • History of substance abuse within the past 2 years
Show all 11Show fewer
  • Serious/chronic systemic or neurological illness (other than AD) such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities
  • Pain or sleep disorder that could interfere with testing
  • Claustrophobia
  • Patients that have received radiation therapy to the head or neck or have been in another research study involving radiation
  • Patients who are unable or unwilling to comply with protocol requirements or deemed by the investigator to be unfit for the study.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Canada8 sites
  • University of Alberta Health Services

    Calgary, Alberta

  • Hamilton General Hospital

    Hamilton, Ontario, L8L 2X2

  • Parkwood Hospital St. Joseph's Health Care

    London, Ontario, N6C 5J1

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • CHU de Sherbrooke

    Québec, Quebec, J1H 5H3

  • CHU de Quebec

    Québec, Quebec

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

  • University of British Columbia Hospital

    Vancouver, British Columbia, V6T 2B5

Other trials in Canada

About this study

The prevalence of both Alzheimer's Disease (AD) and stroke doubles each decade over 65 years old. Both are major causes of dementia, currently estimated to affect 46 million people worldwide. The current costs globally are $818 billion. Additionally, in population studies elders over 65 years, "covert" cerebral small vessel disease appears on MRI scans as silent lacunar infarcts in 25% as Microbleeds in 10%, and as focal or diffuse 'incidental' white matter disease (WMD) in 95%. WMD is extensive in 20%, with a clinical threshold effect around 10cc2. Small vessel disease is even more common in dementia, often coexisting with AD and independently contributing to cognitive decline and progression to dementia. Longitudinal imaging using cerebral amyloid labeling opens a new opportunity to understand the additive/interactive effects of small vessel disease and AD.

The design of this study includes recruitment of two cohorts, including Mild Cognitive Impairment (MCI) and/or early Alzheimer Disease subjects from memory clinics and subjects with strokes/TIA from stroke prevention clinics. Inclusion criteria include the presence of moderate/extensive white matter disease, eg. Fazekas score of 2 (with confluent peri-ventricular hyperintensities) or Fazekas score of 3, as determined by previous MR or CT, > 60 years of age, Mini-Mental Status Exam (MMSE) scores ≥ 20. Subjects will undergo 3T structural MRI (including T1, PD/T2, FLAIR, GRE, DTI, ASL, and resting state fMRI), glucose PET, amyloid PET (using AV-45 florbetapir) and neuropsychological testing, as well as blood sampling. Repeat MR and PET/CT imaging and neuropsychological testing will be conducted at 24 months. The follow up assessments can also be completed at either year 1 or year 3 or Year 4 depending on the availability of study participants. The imaging portion is designed to closely parallel the Alzheimer's Disease Neuroimaging Initiative (ADNI) in order to benefit from the availability of both cognitively normal controls (NC), MCI and Alzheimer's disease subjects with minimal WMD.

Read the detailed description

This study will be a multi-center trial to be conducted in centers across Canada and approximately 80 patients will be enrolled. Participants will be recruited from both stroke prevention (N=40) and memory clinics (N=40). For comparison, we will access the publically-available data using a very similar protocol being collected from normal controls (N=250), MCI (N=250 early MCI, N=150 late MCI) and AD patients (N=150) without significant white matter disease, who are participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI-GO and ADNI 2, N=800), to choose representative samples for comparison to those with scores ≤ 1 who represent the non-white matter disease group.

Three imaging modalities will be used with each participant. 3 Telsa MRI scans will be acquired, using an ADNI based protocol, except for the addition of a PD/T2 interleved sequence. Participants will also undergo 18-fluoro PET with the AVID-45 ligand and 18-fluorodeoxyglucose PET using the ADNI protocols.

The primary objectives are to characterize at baseline and 2-year follow-up in patients with significant Periventricular White Matter Hyperintensities (pvWMH), presenting as transient cerebrovascular events or memory problems, patterns of: 1. Uptake of amyloid on Florbetapir F-18 PET/CT 2. Glucose uptake on 18F-FDG PET/CT 3. Volumetric measures of brain structure on MRI imaging 4. Performance on standard neuropsychological assessments, activities of daily living and gait speed.

Secondary objectives are to: 1. Compare the relationship between amyloid brain uptake, pvWMH volumes, and cognitive scores in patients with significant pvWMH and a control group of individuals that are cognitively normal, MCI or AD, with mild pvWMH, identified from the ADNI database. 2. Examine the relationship between amyloid uptake, ApoE e4 genotype, and structural MRI volumes in patients with a high burden of pvWMH. 3. Evaluate the utility of baseline brain amyloid to predict cognitive decline and increases in pvWMH volume at 2 years follow up. 4. Evaluate the safety of a single intravenous dose of Florbetapir F 18 Injection (370 MBq +/- 10%) in subjects with significant pvWMH.

Keywords
Alzheimer's Disease, White Matter Hyperintensities, Vascular Cognitive Impairment, Amyloid Imaging, Transient Ischemic Attack
Medical subject headings
Alzheimer Disease, Ischemic Attack, Transient

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02330510
Study groupRoleWhat they receive
Alzheimer's DiseaseIndividuals with early Alzheimer's Disease (AD) or amnestic or multi-domain Mild Cognitive Impairment who have extensive Periventricular White Matter Hyperintensities
Transient Ischemic Attack/Mild Subcortical StrokeIndividuals who have had a mild subcortical stroke or a Transient Ischemic Attack (TIA) with extensive Periventricular White Matter Hyperintensities in the absence of cortical infarcts

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in F18 florbetapir SUVR over 2 years in patients with moderate-severe White Matter Hyperintensities, at baseline and 1 year follow-up brain uptake of Florbetapir F 18

    Standardized measures of F18 florbetapir brain uptake will be compared to baseline uptake patterns and prevalence of signal uptake in various areas

    Measured: 24 months

Secondary outcomes (6)
  1. Florbetapir F18 SUVR brain uptake, regional FDG metabolic measures and regional volutmetrics on MRI based volume including grey and white matter, small vessel disease, as well as regional cortical thickness measures.

    Standardized measures of F18 florbetapir brain uptake will be correlated with posterior-cingulate and parietal-temporal metabolism. We will also correlate with hippocampal, ventricular and regional volumes and with cortical thickness, derived with Lesion Explorer enhancement

    Measured: 24 months

  2. F18 florbetapir SUVR brain uptake, with Periventricular White Matter Hyperintensity volumes and cognitive scores.

    The relationship between F18 florbetapir brain uptake, Periventricular White Matter Hyperintensity volumes, executive function and memory scores, in patients with significant pvWMH, accounting for relevant co-variates (age, education), using multivariate analysis including Partial Least Squares (PLS).

    Measured: 24 months

  3. F18 florbetapir brain SUVR uptake, Periventricular White Matter Hyperintensity volumes and cognitive scores in an age-matched group of normal controls, MCI and AD subjects with minimal or mild degrees of pvWMH.

    Mutlivariate analysis will be used to carry out this analysis, including PLS

    Measured: 24 months

  4. F18 florbetapir SUVR brain uptake, ApoE e4 genotype status, and White Matter Hyperintensity volumes in patients with a high burden of pvWMH.

    Measured: 24 months

  5. Baseline F18 florbetapir SUVR brain uptake, cognitive score decline and increase in White Matter Hyperintensity volume at 2 year follow up.

    Measured: 24 months

  6. Assess any adverse events or serious adverse events occurring with a a single intravenous dose of F18 florbetapir Injection (370 MBq +/- 10%) in subjects with significant pvWM

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jan 2015 (estimated)
  2. Study startAug 2014
  3. Primary completion10 Dec 2024
  4. Study completion10 Dec 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02330510
Sponsor's protocol ID
Ml1-112246
Acronym
MITNEC C6
Status last verified
Dec 2024
First submitted
27 Jun 2014
Last updated
16 Dec 2024
Results posted
No
Data monitoring committee
Yes

Publications

  • Xhima K, Ottoy J, Gibson E, Zukotynski K, Scott C, Feliciano GJ, Adamo S, Kuo PH, Borrie MJ, Chertkow H, Frayne R, Laforce R Jr, Noseworthy MD, Prato FS, Sahlas DJ, Smith EE, Sossi V, Thiel A, Soucy JP, Tardif JC, Goubran M, Black SE, Ramirez J; Medical Imaging Trials Network of Canada (MITNEC). Distinct spatial contributions of amyloid pathology and cerebral small vessel disease to hippocampal morphology. Alzheimers Dement. 2024 May;20(5):3687-3695. doi: 10.1002/alz.13791. Epub 2024 Apr 4.

    PubMed 38574400
  • Boone L, Biparva M, Mojiri Forooshani P, Ramirez J, Masellis M, Bartha R, Symons S, Strother S, Black SE, Heyn C, Martel AL, Swartz RH, Goubran M. ROOD-MRI: Benchmarking the robustness of deep learning segmentation models to out-of-distribution and corrupted data in MRI. Neuroimage. 2023 Sep;278:120289. doi: 10.1016/j.neuroimage.2023.120289. Epub 2023 Jul 24.

    PubMed 37495197
  • Ottoy J, Ozzoude M, Zukotynski K, Kang MS, Adamo S, Scott C, Ramirez J, Swardfager W, Lam B, Bhan A, Mojiri P, Kiss A, Strother S, Bocti C, Borrie M, Chertkow H, Frayne R, Hsiung R, Laforce RJ, Noseworthy MD, Prato FS, Sahlas DJ, Smith EE, Kuo PH, Chad JA, Pasternak O, Sossi V, Thiel A, Soucy JP, Tardif JC, Black SE, Goubran M; Medical Imaging Trials Network of Canada (MITNEC) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Amyloid-PET of the white matter: Relationship to free water, fiber integrity, and cognition in patients with dementia and small vessel disease. J Cereb Blood Flow Metab. 2023 Jun;43(6):921-936. doi: 10.1177/0271678X231152001. Epub 2023 Jan 25.

    PubMed 36695071
  • Ottoy J, Ozzoude M, Zukotynski K, Adamo S, Scott C, Gaudet V, Ramirez J, Swardfager W, Cogo-Moreira H, Lam B, Bhan A, Mojiri P, Kang MS, Rabin JS, Kiss A, Strother S, Bocti C, Borrie M, Chertkow H, Frayne R, Hsiung R, Laforce RJ, Noseworthy MD, Prato FS, Sahlas DJ, Smith EE, Kuo PH, Sossi V, Thiel A, Soucy JP, Tardif JC, Black SE, Goubran M; Medical Imaging Trial Network of Canada (MITNEC) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Vascular burden and cognition: Mediating roles of neurodegeneration and amyloid PET. Alzheimers Dement. 2023 Apr;19(4):1503-1517. doi: 10.1002/alz.12750. Epub 2022 Sep 1.

    PubMed 36047604
  • Mojiri Forooshani P, Biparva M, Ntiri EE, Ramirez J, Boone L, Holmes MF, Adamo S, Gao F, Ozzoude M, Scott CJM, Dowlatshahi D, Lawrence-Dewar JM, Kwan D, Lang AE, Marcotte K, Leonard C, Rochon E, Heyn C, Bartha R, Strother S, Tardif JC, Symons S, Masellis M, Swartz RH, Moody A, Black SE, Goubran M. Deep Bayesian networks for uncertainty estimation and adversarial resistance of white matter hyperintensity segmentation. Hum Brain Mapp. 2022 May;43(7):2089-2108. doi: 10.1002/hbm.25784. Epub 2022 Jan 28.

    PubMed 35088930
  • Ntiri EE, Holmes MF, Forooshani PM, Ramirez J, Gao F, Ozzoude M, Adamo S, Scott CJM, Dowlatshahi D, Lawrence-Dewar JM, Kwan D, Lang AE, Symons S, Bartha R, Strother S, Tardif JC, Masellis M, Swartz RH, Moody A, Black SE, Goubran M. Improved Segmentation of the Intracranial and Ventricular Volumes in Populations with Cerebrovascular Lesions and Atrophy Using 3D CNNs. Neuroinformatics. 2021 Oct;19(4):597-618. doi: 10.1007/s12021-021-09510-1. Epub 2021 Feb 1.

    PubMed 33527307

Questions about this trial

What is this clinical trial studying?

An observational study of Alzheimer's Disease and Small Vessel Disease White Matter Hyperintensities Subtype, run by Dr. Sandra E Black at 8 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in F18 florbetapir SUVR over 2 years in patients with moderate-severe White Matter Hyperintensities, at baseline and 1 year follow-up brain uptake of Florbetapir F 18 (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02330510, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2024.

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