AusCADASIL: An Australian Cohort of CADASIL
- Conditions
- Cadasil
- Registration Number
- NCT06148051
- Lead Sponsor
- Perminder Sachdev
- 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Alphabet required for Trail Making A/B 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
Montreal Cognitive Assessment (MoCA) 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
National Institute of Health Computerised Toolbox (NIHCTB) 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
Modified Rankin Scale (mRS) 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)
National Institute of Health Stroke Scale (NIHSS) 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.
Brain MRI scan (total scan time 60 mins)- includes T1 weighted imaging Baseline, Year 3 To assess brain morphology
Brain MRI scan (total scan time 60 mins)- includes resting-state blood oxygenation level dependent (BOLD) imaging. 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
Weight and height will be combined to report BMI in kg/m^2 Baseline, Year 1, Year 2, Year 3, Year 4 Participants will undergo structured physical examination which will provide further details on their clinical profile.
Blood Pressure 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
Category Fluency (animals) 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
Digit Span Backwards (WAIS-IV) 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
Brain MRI scan (total scan time 60 mins)- includes pseudo-continuous arterial spin labelling (PCASL) perfusion imaging with multiple post-labelling delays. Baseline, Year 3 Used to assess quantitative cerebral blood flow and arterial transit time.
Online Medical Questionnaire 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
Letter Fluency (FAS) 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
Rey Auditory Verbal Learning Test (RAVLT) 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
Brain MRI scan (total scan time 60 mins)- includes T2-weighted fluid attenuated inversion recovery (FLAIR) imaging Baseline, Year 3 Combined with T1 outcome to assess brain morphology
Brain MRI scan (total scan time 60 mins)- includes susceptibility-weighted MRI 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.
Brain MRI scan (total scan time 60 mins)- includes multi-shell diffusion weighted MRI 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.
- Secondary Outcome Measures
Name Time Method Study Partner Apathy Evaluation Scale (AES) 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
Instrumental Activities of Daily Living Scale (IADL) Baseline Completed online, 8 items to assess daily living skills in older adults. Outcome will be used to inform clinical profile
Multidimensional Fatigue Inventory (MFI) Baseline Completed online, 20 items to assess physical and mental fatigue and motivation. Outcome will be used to inform clinical profile
Study Partner Instrumental Activities of Daily Living Scale (IADL) 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
Ocular Assessment- Stereopsis Baseline and year 3 The perception of depth will be measured using a stereo acuity instrument by viewing a series of stereograms.
Blood biochemistry 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.
Ocular Questionnaire Baseline, Year 3 Includes questions regarding vision ability and ocular symptoms, and history
Apathy Evaluation Scale (AES) 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
Neuropsychiatric Inventory (NPI-Q) 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
Ocular Assessment-Visual Acuity 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.
Genetic Profile Baseline Genetic testing for NOTCH3 variants as well as potentially modifying genes
Ocular Assessment- Slit-lamp examination 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.
Ocular Assessment- Standard automated perimetry Baseline and year 3 A measure of the sensitivity of the visual field.
Quality of Life Scale (EQ-5D-5L) Baseline Completed online, 6 items to assess mobility, self-care, activities, pain/discomfort, anxiety/depression. Outcome will be used to inform clinical profile
Patient Health Questionnaire-9 (PHQ-9) Baseline Completed online, 9 items to assess depression symptoms and severity. Outcome will be used to inform clinical profile
STOP-BANG Sleep Questionnaire Baseline Completed online, 8 items to assess Obstructive Sleep Apnoea risk. Outcome will be used to inform clinical profile
PROMIS Sleep Disturbance Baseline Completed online, 8 items to assess sleep quality. Outcome will be used to inform clinical profile
Hospital Anxiety and Depression Scale (HADS) Baseline Completed online, includes 14 items to assess non-physical symptoms of anxiety and depression. Outcome will be used to inform clinical profile
Blood Omic investigation Baseline and year 3 Blood tubes will be transported to the University of New South Wales for genomics, proteomics, lipidomics, and epigenomics analysis
Ocular Assessment- Contrast Sensitivity Baseline and year 3 A measure of vision function, relating to the ability to distinguish between an object and the background behind it.
Ocular Assessment- Intraocular pressure Baseline and year 3 A measure of the pressure within the eye.
Ocular Assessment- Fundus imaging (requires pupil dilation using tropicamide 0.5 or 1.0% eye drops Baseline and year 3 Used to visualise the back of the eye
Ocular Assessment- Optical Coherence Tomography (OCT) and OCT-Angiography Baseline and year 3 Used to visualise the back of the eye in retinal layers, and the retinal vessels
Trial Locations
- Locations (5)
Prince of Wales Hospital
🇦🇺Sydney, New South Wales, Australia
University of New South Wales
🇦🇺Sydney, New South Wales, Australia
John Hunter Hospital
🇦🇺Newcastle, New South Wales, Australia
Royal Brisbane and Women's Hospital
🇦🇺Brisbane, Queensland, Australia
Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia