Amyloid-related Imaging Abnormalities (Microbleeds) in Atypical AD

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Mayo Clinic
Sponsor:
Information provided by (Responsible Party):
Jennifer Whitwell, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01723553
First received: November 6, 2012
Last updated: June 25, 2014
Last verified: October 2013
  Purpose

The study is designed to assess the demographic, clinical and imaging associations with the presence of microbleeds in atypical Alzheimer's disease. The primary hypothesis is that cognitive and functional performance will be poorer in atypical Alzheimer's subjects with microbleeds compared to those without microbleeds.


Condition Intervention
Atypical Alzheimers Disease
Logopenic Variant of Primary Progressive Aphasia (LPA)
Posterior Cortical Atrophy (PCA)
Drug: C-11 PiB

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Amyloid-related Imaging Abnormalities (Microbleeds) in Atypical AD

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Proportion of subjects with and without microbleeds [ Time Frame: up to day 2 of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of white matter hyperintensity burden on MRI and ratio of amyloid burden on PiB PET scan [ Time Frame: Study entry, approximately day 1 or day 2 of study ] [ Designated as safety issue: No ]
  • Number of microbleeds per subject [ Time Frame: Study entry, approximately day 1 or day 2 of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: November 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PiB positron emission tomography (PET)
All subjects will receive PiB PET imaging on approximately day 1 or day 2 of study to determine if they have beta-amyloid deposits in their brains.
Drug: C-11 PiB
One time intravenous administration of ~740 megabecquerel (MBq) of [N-methyl-C-11]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PiB) (range 370 - 740 MBq).
Other Names:
  • Pittsburgh Compound B
  • PiB

Detailed Description:

Alzheimer's disease (AD) is associated with amyloid-related imaging abnormalities (ARIA). Microbleeds (MBs) represent part of the spectrum of ARIA and can be identified as small hypointense lesions on gradient-recalled echo (GRE) T2*-weighted MRI. They are thought to represent hemosiderin deposits (and hence have been classified as ARIA-H1) and occur as a consequence of leakage of blood products out of vessels that have been damaged by deposition of the protein β-amyloid in cerebral vessels; cerebral amyloid angiopathy (CAA). However, it is also possible that cerebrovascular disease could contribute to the presence of MBs in AD. Subjects with MBs are at a greater risk of bleeds which could impact the use of anti-coagulation treatment approaches.

The presence of CAA has been particularly associated with AD and studies have demonstrated that MBs occur in 12-33% of subjects with typical Alzheimer's dementia, with a large proportion of subjects showing multiple MBs. The presence of MBs has been associated with older age and a greater degree of white matter hyperintensities (WMH) in Alzheimer's dementia. The association between MBs and WMH, a marker of cerebrovascular disease, suggests cerebrovascular disease may also play a role in the etiology of MBs in AD. However, approximately 16% of AD subjects do not present with episodic memory loss, but instead display language problems such as poor naming and impaired sentence repetition, or visuospatial and visual perceptual deficits, and are referred to as atypical AD. Since AD is associated with CAA, one would assume that CAA and hence MBs, would also occur in atypical AD, although no studies have assessed MBs in atypical AD.

Amyloid-binding ligands, such as Pittsburgh Compound B (PiB), that can be detected using PET scanning have now been developed and provide an invaluable biomarker to infer the presence of β-amyloid. The presence of CAA has been shown to be associated with elevated PiB uptake, and hence the assessment of PiB-PET in subjects with MBs will provide important information on the association of MBs and β-amyloid deposition in AD.

The goal of the study is to assess the associations between MBs and demographic/clinical features, assess the associations between MBs and imaging features as well as a possible correlate to the number of MBs a subject has in atypical AD.

Patients found to be eligible and willing to enroll in this study will be asked to undergo a Neurologic Examination, Neuropsychometric testing, an MRI scan, and a PiB PET scan of the brain. This will be done over a period of two days at the Mayo Clinic in Rochester, Minnesota.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • over the age of 21
  • will have an informant/study partner who will be able to provide independent evaluation of functioning
  • must fulfill clinical diagnostic criteria for atypical AD, and hence should either have a chief complaint of difficulty with language and fulfill criteria for logopenic variant of primary progressive aphasia, or present with visuospatial/perceptual deficits and fulfill criteria for posterior cortical atrophy
  • speaks English as their primary language (including bilingual patients whose primary language is English)
  • agrees to and is eligible to undergo MRI and PET scanning
  • if woman of child bearing age, must agree to pregnancy test no more than 48 hours before the PET scans

Exclusion Criteria:

  • subjects with concurrent illnesses that could account for the presenting syndrome, such as traumatic brain injury, strokes or developmental syndromes
  • subjects meeting criteria for another neurodegenerative disease, particularly typical Alzheimer's dementia
  • women that are pregnant or post-partum and breast-feeding
  • subjects will also be excluded if MRI is contraindicated (metal in head, cardiac pace maker, e.t.c.), if there is severe claustrophobia, and if there are conditions that may confound brain imaging studies (e.g. structural abnormalities, including subdural hematoma or intracranial neoplasm)
  • subjects will also be excluded if they do not have an informant, do not consent to research or do not complete all components of the study (neurological exam, neuropsychometric tests, MRI, PiB PET)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01723553

Contacts
Contact: Sarah Boland 507-293-4707 boland.sarah@mayo.edu

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Sarah Boland    507-293-4707    boland.sarah@mayo.edu   
Sub-Investigator: Keith A Josephs, MD, MST, MSc         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Jennifer Whitwell, PhD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Jennifer Whitwell, PI, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01723553     History of Changes
Other Study ID Numbers: 12-007139
Study First Received: November 6, 2012
Last Updated: June 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
aphasia
logopenic
PCA
LPA

Additional relevant MeSH terms:
Pick Disease of the Brain
Brain Diseases
Alzheimer Disease
Aphasia
Aphasia, Primary Progressive
Frontotemporal Dementia
Dementia
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Frontotemporal Lobar Degeneration
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases

ClinicalTrials.gov processed this record on September 30, 2014