AusCADASIL: An Australian Cohort of CADASIL

Cadasil Clinical Trial

Official title:

AusCADASIL: An Australian Cohort of CADASIL

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06148051
• Other study ID #: AusCADASIL
• Status: Recruiting
• Start date: November 25, 2023
• Est. completion date: March 31, 2027

Study information

• Verified date: May 2024
• Source: The University of New South Wales
• Contact: Danit Saks, MBMSc, MRes, PhD
• Phone: 9348 1658
• Email: d.saks[@]unsw.edu.au
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: March 31, 2027
• Est. primary completion date: March 31, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Adults =18 years old

2. 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

3. Ability to attend a testing site

4. Ability to complete minimum dataset (medical examination and medical history questionnaire, blood test to determine genetic status and a short (20 minute) neuropsychology assessment).

5. CADASIL participants according to one of the following categories:

1. confirmed diagnosis via genetic testing (NOTCH3 pathogenic variant), OR

2. suspected diagnosis based on medical history and brain MRI, OR

3. 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:

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

Related Conditions & MeSH terms

• Cadasil
• Dementia, Multi-Infarct

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital	Brisbane	Queensland
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	John Hunter Hospital	Newcastle	New South Wales
Australia	Prince of Wales Hospital	Sydney	New South Wales
Australia	University of New South Wales	Sydney	New South Wales

Sponsors (7)

Lead Sponsor	Collaborator
Perminder Sachdev	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

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Brain MRI scan (total scan time 60 mins)- includes T1 weighted imaging	To assess brain morphology	Baseline, Year 3
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Blood biochemistry	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.	Baseline, Year 3
Secondary	Ocular Questionnaire	Includes questions regarding vision ability and ocular symptoms, and history	Baseline, Year 3
Secondary	Genetic Profile	Genetic testing for NOTCH3 variants as well as potentially modifying genes	Baseline
Secondary	Instrumental Activities of Daily Living Scale (IADL)	Completed online, 8 items to assess daily living skills in older adults. Outcome will be used to inform clinical profile	Baseline
Secondary	Quality of Life Scale (EQ-5D-5L)	Completed online, 6 items to assess mobility, self-care, activities, pain/discomfort, anxiety/depression. Outcome will be used to inform clinical profile	Baseline
Secondary	STOP-BANG Sleep Questionnaire	Completed online, 8 items to assess Obstructive Sleep Apnoea risk. Outcome will be used to inform clinical profile	Baseline
Secondary	PROMIS Sleep Disturbance	Completed online, 8 items to assess sleep quality. Outcome will be used to inform clinical profile	Baseline
Secondary	Apathy Evaluation Scale (AES)	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	Baseline
Secondary	Multidimensional Fatigue Inventory (MFI)	Completed online, 20 items to assess physical and mental fatigue and motivation. Outcome will be used to inform clinical profile	Baseline
Secondary	Patient Health Questionnaire-9 (PHQ-9)	Completed online, 9 items to assess depression symptoms and severity. Outcome will be used to inform clinical profile	Baseline
Secondary	Hospital Anxiety and Depression Scale (HADS)	Completed online, includes 14 items to assess non-physical symptoms of anxiety and depression. Outcome will be used to inform clinical profile	Baseline
Secondary	Study Partner Apathy Evaluation Scale (AES)	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	Baseline
Secondary	Study Partner Instrumental Activities of Daily Living Scale (IADL)	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	Baseline
Secondary	Neuropsychiatric Inventory (NPI-Q)	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	Baseline
Secondary	Blood Omic investigation	Blood tubes will be transported to the University of New South Wales for genomics, proteomics, lipidomics, and epigenomics analysis	Baseline and year 3
Secondary	Ocular Assessment-Visual Acuity	a measure of the vision function using high contrast letters will be performed with standardised vision charts at distance and at near.	Baseline and year 3
Secondary	Ocular Assessment- Contrast Sensitivity	A measure of vision function, relating to the ability to distinguish between an object and the background behind it.	Baseline and year 3
Secondary	Ocular Assessment- Stereopsis	The perception of depth will be measured using a stereo acuity instrument by viewing a series of stereograms.	Baseline and year 3
Secondary	Ocular Assessment- Slit-lamp examination	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.	Baseline and year 3
Secondary	Ocular Assessment- Standard automated perimetry	A measure of the sensitivity of the visual field.	Baseline and year 3
Secondary	Ocular Assessment- Intraocular pressure	A measure of the pressure within the eye.	Baseline and year 3
Secondary	Ocular Assessment- Fundus imaging (requires pupil dilation using tropicamide 0.5 or 1.0% eye drops	Used to visualise the back of the eye	Baseline and year 3
Secondary	Ocular Assessment- Optical Coherence Tomography (OCT) and OCT-Angiography	Used to visualise the back of the eye in retinal layers, and the retinal vessels	Baseline and year 3