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NCT Number: NCT06148051

AusCADASIL: An Australian Cohort of CADASIL

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

John Hunter Hospital, Newcastle, New South Wales, Australia

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About this study

Using clinical examination, questionnaires, neuropsychological evaluation, brain MRI, blood sample evaluation and retinal imaging, we aim to characterise the clinical profile and progression of CADASIL in an Australian cohort.

This is multi-centre observational cohort study currently based at six sites (clinics, hospitals and universities) across three states in Australia (New South Wales, Victoria and Queensland). The multidisciplinary team aims to be the first to develop an Australian cohort of CADASIL which will contribute to global efforts and understanding of the disease.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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)

Exclusion criteria

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

Treatment and study plan

Primary outcomes

  1. Online Medical Questionnaire

    Time frame: Baseline, Year 1, Year 2, Year 3, Year 4

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

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

    Time frame: Baseline, Year 1, Year 2, Year 3, Year 4

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

  3. Blood Pressure

    Time frame: Baseline, Year 1, Year 2, Year 3, Year 4

    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

  4. Modified Rankin Scale (mRS)

    Time frame: Baseline, Year 1, Year 2, Year 3, Year 4

    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)

  5. National Institute of Health Stroke Scale (NIHSS)

    Time frame: Baseline, Year 1, Year 2, Year 3, Year 4

    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.

  6. Alphabet required for Trail Making A/B

    Time frame: Baseline, Year 1, Year 2, Year 3, Year 4

    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

  7. Montreal Cognitive Assessment (MoCA)

    Time frame: Baseline, Year 1, Year 2, Year 3, Year 4

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

  8. Category Fluency (animals)

    Time frame: Baseline, Year 1, Year 2, Year 3, Year 4

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

  9. Digit Span Backwards (WAIS-IV)

    Time frame: Baseline, Year 1, Year 2, Year 3, Year 4

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

  10. National Institute of Health Computerised Toolbox (NIHCTB)

    Time frame: Baseline, Year 1, Year 2, Year 3, Year 4

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

  11. Letter Fluency (FAS)

    Time frame: Baseline, Year 1, Year 2, Year 3, Year 4

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

  12. Rey Auditory Verbal Learning Test (RAVLT)

    Time frame: Baseline, Year 1, Year 2, Year 3, Year 4

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

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

    Time frame: Baseline, Year 3

    To assess brain morphology

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

    Time frame: Baseline, Year 3

    Combined with T1 outcome to assess brain morphology

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

    Time frame: Baseline, Year 3

    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.

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

    Time frame: Baseline, Year 3

    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.

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

    Time frame: Baseline, Year 3

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

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

    Time frame: Baseline, Year 3

    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

Secondary outcomes

  1. Blood biochemistry

    Time frame: Baseline, Year 3

    Analysed by local pathology lab to indicate clinical profile. Measures will include fasting glucose, HbA1c, lipids, C-reactive protein, creatinine, vit D and liver function tests.

  2. Ocular Questionnaire

    Time frame: Baseline, Year 3

    Includes questions regarding vision ability and ocular symptoms, and history

  3. Genetic Profile

    Time frame: Baseline

    Genetic testing for NOTCH3 variants as well as potentially modifying genes

  4. Instrumental Activities of Daily Living Scale (IADL)

    Time frame: Baseline

    Completed online, 8 items to assess daily living skills in older adults. Outcome will be used to inform clinical profile

  5. Quality of Life Scale (EQ-5D-5L)

    Time frame: Baseline

    Completed online, 6 items to assess mobility, self-care, activities, pain/discomfort, anxiety/depression. Outcome will be used to inform clinical profile

  6. STOP-BANG Sleep Questionnaire

    Time frame: Baseline

    Completed online, 8 items to assess Obstructive Sleep Apnoea risk. Outcome will be used to inform clinical profile

  7. PROMIS Sleep Disturbance

    Time frame: Baseline

    Completed online, 8 items to assess sleep quality. Outcome will be used to inform clinical profile

  8. Apathy Evaluation Scale (AES)

    Time frame: Baseline

    Completed online, 18 items to assess apathy by goal-directed behaviour, goal-related cognition, and goal-related emotional responses. Outcome will be used to inform clinical profile

  9. Multidimensional Fatigue Inventory (MFI)

    Time frame: Baseline

    Completed online, 20 items to assess physical and mental fatigue and motivation. Outcome will be used to inform clinical profile

  10. Patient Health Questionnaire-9 (PHQ-9)

    Time frame: Baseline

    Completed online, 9 items to assess depression symptoms and severity. Outcome will be used to inform clinical profile

  11. Hospital Anxiety and Depression Scale (HADS)

    Time frame: Baseline

    Completed online, includes 14 items to assess non-physical symptoms of anxiety and depression. Outcome will be used to inform clinical profile

  12. Study Partner Apathy Evaluation Scale (AES)

    Time frame: Baseline

    Completed online by nominated study partner (someone who knows the participant well e.g. spouse, carer, friend etc). Inform's participant's apathy by goal-directed behaviour, goal-related cognition, and goal-related emotional responses

  13. Study Partner Instrumental Activities of Daily Living Scale (IADL)

    Time frame: Baseline

    Completed online by nominated study partner (someone who knows the participant well e.g. spouse, carer, friend etc). 8 items to assess daily living skills in older adults. Outcome will be used to inform participant's clinical profile

  14. Neuropsychiatric Inventory (NPI-Q)

    Time frame: Baseline

    Completed online by nominated study partner (someone who knows the participant well e.g. spouse, carer, friend etc). 12 domains, approx. 100 questions. Used to inform psychopathology in participants

  15. Blood Omic investigation

    Time frame: Baseline and year 3

    Blood tubes will be transported to the University of New South Wales for genomics, proteomics, lipidomics, and epigenomics analysis

  16. Ocular Assessment-Visual Acuity

    Time frame: Baseline and year 3

    a measure of the vision function using high contrast letters will be performed with standardised vision charts at distance and at near.

  17. Ocular Assessment- Contrast Sensitivity

    Time frame: Baseline and year 3

    A measure of vision function, relating to the ability to distinguish between an object and the background behind it.

  18. Ocular Assessment- Stereopsis

    Time frame: Baseline and year 3

    The perception of depth will be measured using a stereo acuity instrument by viewing a series of stereograms.

  19. Ocular Assessment- Slit-lamp examination

    Time frame: Baseline and year 3

    Involves viewing of the ocular structures using a slit-lamp illumination system and biomicroscope viewing system. The slit-lamp examination will be conducted by a trained observer and will allow identification of ocular media opacities, abnormalities of the eye lids, tear film and anterior structures.

  20. Ocular Assessment- Standard automated perimetry

    Time frame: Baseline and year 3

    A measure of the sensitivity of the visual field.

  21. Ocular Assessment- Intraocular pressure

    Time frame: Baseline and year 3

    A measure of the pressure within the eye.

  22. Ocular Assessment- Fundus imaging (requires pupil dilation using tropicamide 0.5 or 1.0% eye drops

    Time frame: Baseline and year 3

    Used to visualise the back of the eye

  23. Ocular Assessment- Optical Coherence Tomography (OCT) and OCT-Angiography

    Time frame: Baseline and year 3

    Used to visualise the back of the eye in retinal layers, and the retinal vessels

Study contacts

Contact information is provided by the study sponsor or research team.

Danit Saks, MBMSc, MRes, PhD

CONTACT

[email protected]

9348 1658 ext. +612

Sponsors and collaborators

Lead sponsor

Perminder Sachdev

Other

Collaborators

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

Registry information

Important dates

Study start
2023
Primary completion
2027
Study completion
2027
First posted
Nov 28, 2023
Registry last updated
May 8, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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