AusCADASIL: An Australian Cohort of CADASIL

NCT06148051 | Recruiting DMC

• 1 other identifier: AusCADASIL
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 5

Brief Summary

The aim of this project is to establish an Australian cohort of patients diagnosed with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). This study will examine the clinical features and longitudinal course of CADASIL. Outcome measures include neuropsychological profile, neuroimaging, genetics, blood biomarkers, and retinal imaging.

Conditions

Cadasil

Keywords

CADASIL; Clinical Research; Genetics; Cognition; Neuroimaging; Blood markers; Retinal imaging

Outcome Measures

Primary Outcomes (18)

• Online Medical Questionnaire

  Includes questions on participant's medical history (CADASIL and other), family history, and medication use. Outcome will be used to inform clinical profile

  Baseline, Year 1, Year 2, Year 3, Year 4

• Weight and height will be combined to report BMI in kg/m^2

  Participants will undergo structured physical examination which will provide further details on their clinical profile.

  Baseline, Year 1, Year 2, Year 3, Year 4

• Blood Pressure

  Participants will undergo structured physical examination which will provide further details on their clinical profile. Systolic/diastolic blood pressure will be recorded 3 times during the physical examination

  Baseline, Year 1, Year 2, Year 3, Year 4

• Modified Rankin Scale (mRS)

  Participants will undergo structured physical examination which will provide further details on their clinical profile. Scale from 0-5 (0 no symptoms, 5 severe disability)

  Baseline, Year 1, Year 2, Year 3, Year 4

• National Institute of Health Stroke Scale (NIHSS)

  Participants will undergo structured physical examination which will provide further details on their clinical profile. Individual items (11) relating to stroke symptoms and disability, for each item 0 indicates normal.

  Baseline, Year 1, Year 2, Year 3, Year 4

• Alphabet required for Trail Making A/B

  As part of the neuropsychological battery, participants will need to complete the alphabet to inform ability to complete Trail Making tests A and B. These indicate executive function

  Baseline, Year 1, Year 2, Year 3, Year 4

• Montreal Cognitive Assessment (MoCA)

  As part of the neuropsychological battery, participants will complete the MoCA to provide a measure of global cognitive function

  Baseline, Year 1, Year 2, Year 3, Year 4

• Category Fluency (animals)

  As part of the neuropsychological battery, participants will complete Category Fluency to provide a measure of processing speed

  Baseline, Year 1, Year 2, Year 3, Year 4

• Digit Span Backwards (WAIS-IV)

  As part of the neuropsychological battery, participants will complete digit span backwards to provide a measure of executive function

  Baseline, Year 1, Year 2, Year 3, Year 4

• National Institute of Health Computerised Toolbox (NIHCTB)

  As part of the neuropsychological battery, participants will complete the NIHCTB to provide measures of global function

  Baseline, Year 1, Year 2, Year 3, Year 4

• Letter Fluency (FAS)

  As part of the neuropsychological battery, participants will complete the FAS to provide measures of executive function

  Baseline, Year 1, Year 2, Year 3, Year 4

• Rey Auditory Verbal Learning Test (RAVLT)

  As part of the neuropsychological battery, participants will complete the RAVLT to provide measures of learning and memory

  Baseline, Year 1, Year 2, Year 3, Year 4

• Brain MRI scan (total scan time 60 mins)- includes T1 weighted imaging

  To assess brain morphology

  Baseline, Year 3

• Brain MRI scan (total scan time 60 mins)- includes T2-weighted fluid attenuated inversion recovery (FLAIR) imaging

  Combined with T1 outcome to assess brain morphology

  Baseline, Year 3

• Brain MRI scan (total scan time 60 mins)- includes susceptibility-weighted MRI

  Assesses cerebral microbleeds. Signal magnitude will be processed to estimate signal decay time (i.e., T2\* maps), which reflect compartmentalisation of magnetised tissue constituents (iron, calcium) \[22\]. Signal phase will be processed for quantitative susceptibility mapping.

  Baseline, Year 3

• Brain MRI scan (total scan time 60 mins)- includes multi-shell diffusion weighted MRI

  Measures of brain white matter microstructural integrity, such as fractional anisotropy and mean diffusivity, will be calculated using tensor models. Fixel-based analyses of fibre density and cross-section will also be performed. Markers of cerebrovascular diseases derived from diffusion data, such as Peak width of Skeletonised Mean Diffusivity (PSMD), will be calculated. Structural connectivity will also be examined.

  Baseline, Year 3

• Brain MRI scan (total scan time 60 mins)- includes pseudo-continuous arterial spin labelling (PCASL) perfusion imaging with multiple post-labelling delays.

  Used to assess quantitative cerebral blood flow and arterial transit time.

  Baseline, Year 3

• Brain MRI scan (total scan time 60 mins)- includes resting-state blood oxygenation level dependent (BOLD) imaging.

  Used to assess brain functional activity and amplitude of low-frequency fluctuations which embeds signal of cerebrovascular reactivity. For sites with available capnography monitors, participants' end-tidal carbon dioxide concentrations will be recorded during acquiring resting-state BOLD data for more accurate quantification of cerebrovascular reactivity

  Baseline, Year 3

Secondary Outcomes (23)

• Blood biochemistry

  Baseline, Year 3

• Ocular Questionnaire

  Baseline, Year 3

• Genetic Profile

  Baseline

• Instrumental Activities of Daily Living Scale (IADL)

  Baseline

• Quality of Life Scale (EQ-5D-5L)

  Baseline

Study Arms (2)

CADASIL cohort

Control Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with CADASIL confirmed by genetic testing, suspected due to clinical symptoms, or family history of CADASIL. Control cohort will be negative for the NOTCH3 pathogenic variant and have no cognitive complaints

You may qualify if:

• Adults ≥18 years old
• Ability to provide written informed consent
• A large-print version is available for individuals with visual impairment
• An easy-to-read version is available for individuals with cognitive difficulties who may require extra support
• Ability to attend a testing site
• Ability to complete minimum dataset (medical examination and medical history questionnaire, blood test to determine genetic status and a short (20 minute) neuropsychology assessment).
• CADASIL participants according to one of the following categories:
• confirmed diagnosis via genetic testing (NOTCH3 pathogenic variant), OR
• suspected diagnosis based on medical history and brain MRI, OR
• first degree relative of participant who is positive for NOTCH3 pathogenic variant
• OR 6. Unrelated individual who is negative for the NOTCH3 pathogenic variant, and has no cognitive complaints (i.e. control participant)

You may not qualify if:

• \. Significant cognitive impairment leading to an inability to provide informed consent.

Sponsors & Collaborators

• Perminder Sachdev: lead
• Prince of Wales Hospital, Sydney: collaborator
• John Hunter Hospital: collaborator
• St Vincent's Hospital - Sydney, Australia: collaborator
• Royal Brisbane and Women's Hospital: collaborator
• Melbourne Health: collaborator
• The University of Queensland: collaborator

Study Sites (5)

John Hunter Hospital

Newcastle, New South Wales, 2305, Australia

RECRUITING

Prince of Wales Hospital

Sydney, New South Wales, 2031, Australia

RECRUITING

University of New South Wales

Sydney, New South Wales, 2031, Australia

RECRUITING

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4006, Australia

NOT YET RECRUITING

Royal Melbourne Hospital

Melbourne, Victoria, 3052, Australia

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples

MeSH Terms

Conditions

CADASIL

Condition Hierarchy (Ancestors)

Cerebral Infarction; Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Dementia, Vascular; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Stroke; Dementia; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Officials

• Perminder S Sachdev, MBBS, MD, PhD, FRANZCP, FAAHMS

  University of New South Wales

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Danit Saks, MBMSc, MRes, PhD

CONTACT

9348 1658; d.saks@unsw.edu.au

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 7, 2023
• First Posted: November 28, 2023
• Study Start: November 25, 2023
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: May 8, 2024

Record last verified: 2024-05

Locations

AU (5)