Clinical trial NCT06148051: AusCADASIL: An Australian Cohort of CADASIL
Official title: AusCADASIL: An Australian Cohort of CADASIL
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cadasil
Keywords: CADASIL
Clinical Research
Genetics
Cognition
Neuroimaging
Blood markers
Retinal imaging
Lead sponsor: The University of New South Wales
Sponsor class: OTHER
Collaborators: name: Prince of Wales Hospital, Sydney
name: John Hunter Hospital
name: St Vincent's Hospital - Sydney, Australia
name: Royal Brisbane and Women's Hospital
name: Melbourne Health
name: The University of Queensland
First posted: 2023-11-28
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Online Medical Questionnaire
timeFrame: Baseline, Year 1, Year 2, Year 3, Year 4
measure: Weight and height will be combined to report BMI in kg/m^2
timeFrame: Baseline, Year 1, Year 2, Year 3, Year 4
measure: Blood Pressure
timeFrame: Baseline, Year 1, Year 2, Year 3, Year 4
measure: Modified Rankin Scale (mRS)
timeFrame: Baseline, Year 1, Year 2, Year 3, Year 4
measure: National Institute of Health Stroke Scale (NIHSS)
timeFrame: Baseline, Year 1, Year 2, Year 3, Year 4
measure: Alphabet required for Trail Making A/B
timeFrame: Baseline, Year 1, Year 2, Year 3, Year 4
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: Baseline, Year 1, Year 2, Year 3, Year 4
measure: Category Fluency (animals)
timeFrame: Baseline, Year 1, Year 2, Year 3, Year 4
measure: Digit Span Backwards (WAIS-IV)
timeFrame: Baseline, Year 1, Year 2, Year 3, Year 4
measure: National Institute of Health Computerised Toolbox (NIHCTB)
timeFrame: Baseline, Year 1, Year 2, Year 3, Year 4
measure: Letter Fluency (FAS)
timeFrame: Baseline, Year 1, Year 2, Year 3, Year 4
measure: Rey Auditory Verbal Learning Test (RAVLT)
timeFrame: Baseline, Year 1, Year 2, Year 3, Year 4
measure: Brain MRI scan (total scan time 60 mins)- includes T1 weighted imaging
timeFrame: Baseline, Year 3
measure: Brain MRI scan (total scan time 60 mins)- includes T2-weighted fluid attenuated inversion recovery (FLAIR) imaging
timeFrame: Baseline, Year 3
measure: Brain MRI scan (total scan time 60 mins)- includes susceptibility-weighted MRI
timeFrame: Baseline, Year 3
measure: Brain MRI scan (total scan time 60 mins)- includes multi-shell diffusion weighted MRI
timeFrame: Baseline, Year 3
measure: Brain MRI scan (total scan time 60 mins)- includes pseudo-continuous arterial spin labelling (PCASL) perfusion imaging with multiple post-labelling delays.
timeFrame: Baseline, Year 3
measure: Brain MRI scan (total scan time 60 mins)- includes resting-state blood oxygenation level dependent (BOLD) imaging.
timeFrame: Baseline, Year 3
Secondary outcomes:
measure: Blood biochemistry
timeFrame: Baseline, Year 3
measure: Ocular Questionnaire
timeFrame: Baseline, Year 3
measure: Genetic Profile
timeFrame: Baseline
measure: Instrumental Activities of Daily Living Scale (IADL)
timeFrame: Baseline
measure: Quality of Life Scale (EQ-5D-5L)
timeFrame: Baseline
measure: STOP-BANG Sleep Questionnaire
timeFrame: Baseline
measure: PROMIS Sleep Disturbance
timeFrame: Baseline
measure: Apathy Evaluation Scale (AES)
timeFrame: Baseline
measure: Multidimensional Fatigue Inventory (MFI)
timeFrame: Baseline
measure: Patient Health Questionnaire-9 (PHQ-9)
timeFrame: Baseline
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: Baseline
measure: Study Partner Apathy Evaluation Scale (AES)
timeFrame: Baseline
measure: Study Partner Instrumental Activities of Daily Living Scale (IADL)
timeFrame: Baseline
measure: Neuropsychiatric Inventory (NPI-Q)
timeFrame: Baseline
measure: Blood Omic investigation
timeFrame: Baseline and year 3
measure: Ocular Assessment-Visual Acuity
timeFrame: Baseline and year 3
measure: Ocular Assessment- Contrast Sensitivity
timeFrame: Baseline and year 3
measure: Ocular Assessment- Stereopsis
timeFrame: Baseline and year 3
measure: Ocular Assessment- Slit-lamp examination
timeFrame: Baseline and year 3
measure: Ocular Assessment- Standard automated perimetry
timeFrame: Baseline and year 3
measure: Ocular Assessment- Intraocular pressure
timeFrame: Baseline and year 3
measure: Ocular Assessment- Fundus imaging (requires pupil dilation using tropicamide 0.5 or 1.0% eye drops
timeFrame: Baseline and year 3
measure: Ocular Assessment- Optical Coherence Tomography (OCT) and OCT-Angiography
timeFrame: Baseline and year 3
Other outcomes:
Locations:
city: Newcastle
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Sydney
country: Australia
facility: University of New South Wales
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
Study officials:
affiliation: University of New South Wales
name: Perminder S Sachdev, MBBS, MD, PhD, FRANZCP, FAAHMS
role: PRINCIPAL_INVESTIGATOR
References: