Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000008628
Ethics application status
Approved
Date submitted
23/11/2022
Date registered
9/01/2023
Date last updated
9/01/2023
Date data sharing statement initially provided
9/01/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Australian Epilepsy Project
Scientific title
Australian Epilepsy Project - A project developing improved epilepsy diagnostics and prognostics through advanced imaging, neuropsychology and genetics for people with epilepsy
Secondary ID [1] 307173 0
nil known
Universal Trial Number (UTN)
U1111-1278-4634
Trial acronym
AEP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 326382 0
Condition category
Condition code
Neurological 323677 323677 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Advanced MRI, Neuropsychological Assessment and genetic testing.

The study requires a single MRI acquisition which will be performed as a 90-minute session, with an optional out-of-scanner break of up to 15 minutes during the session. In overview, the acquisition will include structural imaging (comparable to a clinical epilepsy baseline MRI) as well as functional, diffusion and quantitative imaging sequences. The imaging plan will be the same for all participants. No injected contrast agents will be used in the study. Participants will be asked to complete various tasks while inside the MRI Scanner such as responding to images by pushing buttons and watching select video images.

The MRI's will be conducted at selected Hubs around Australia by experienced radiographers trained in the conduct of the study.

A package of Neuropsychological Assessment will be delivered via telehealth by trained neuropsychologists at the start of the study. the battery of tests used will include 10 tests to be administered in less than two hours. The battery is aimed at cognitive domains particularly important in Epilepsy. Examples of the tests are Trail making, verbal fluency and digit span tests.

The Genetic testing will be a chromosomal microarray looking at changes that can contribute to epilepsy and a biobanking sample. This will occur at the baseline of the study and require a nasal swab and blood test. the testing will be performed by trained study personnel at each hub.
The testing will be timed to coincide with the availability of MRI Scanning and will be flexibly scheduled depending on participant availability and convenience. These tests are not repeated after baseline.

Study staff will keep records of participation and ensure all activities are conducted and checked on the project database
Intervention code [1] 323625 0
Early detection / Screening
Comparator / control treatment
no control group. Normative controls that are healthy volunteers are to be recruited for imaging and neuropsychiatric analysis. Although the AEP is a longitudinal cohort study rather than a case-control, a small number of healthy volunteers without epilepsy will be recruited. These participants are included not as an overall comparison group but rather to allow normalisation of individual neuropsychological and MRI analyses, as well as comparison between scanners for harmonising the data.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 331528 0
Accumulation of predictive data sets that inform and enable the creation of reports to enable the the development of a predictive algorithm to assist with diagnosis/prognosis of participants with epilepsy. This is assessed through MRI scans, genetic testing, neuropsychological testing and medical history collection
Timepoint [1] 331528 0
Assessed yearly for 2 years post enrolment
Secondary outcome [1] 410188 0
Seizure freedom rate for the study population compared to a historical baseline of the participant's seizures as assessed by seizure diaries and medical history
Timepoint [1] 410188 0
Assessed yearly for 2 years post enrolment
Secondary outcome [2] 410189 0
Change in QOLIE (Quality of Life in Epilepsy) measures from baseline to project completion
Timepoint [2] 410189 0
Assessed at 6 months, 12 months and 24 months post enrolment

Eligibility
Key inclusion criteria
Inclusion criteria
- Able to consent for themselves
- Over 18 and less than 65 years of age
- Able to understand the process of the study
- Fluent in English
- Referred by a Neurologist AND an EEG has been ordered or completed
- First-ever seizure cohort
- Diagnosis made no more than 3 months before referral
- Participants must have only ever had one unprovoked seizure, or cluster of seizures on a single day, that occurred no more than 6 months before referral
- Participants can be included with:
- Past history of febrile seizures
- Past history of provoked seizure(s) as per the ILAE (International League Against
Epilepsy) definition 86

New diagnosis of epilepsy cohort
- At least two unprovoked seizures (over any time frame, the most recent within 6 months of referral)
- Diagnosis of epilepsy made within 6 months of referral
OR
One seizure within 6 months of referral AND one or more of;
- Epileptiform discharges on EEG
- Epileptogenic lesion on CT
- Epileptogenic lesion on MRI
- Untreated or treated with anti-seizure medications (ASM) for less than 6 months at the time of referral

Drug-resistant epilepsy cohort
- Focal (or combined focal and generalised) epilepsy, with or without likely causative lesion on MRI
- At least one seizure in the 6 months prior to referral
- Two appropriate drugs in adequate doses have failed due to lack of efficacy (‘appropriate’ and ‘adequate’ as decided by the treating neurologist), including previous and current ASMs (e.g. on 1 current ASM and previously failed 1 or more ASM, or on 2 or more current ASMs)87
- Currently taking at least one ASM

Healthy Volunteers inclusion criteria:
Inclusion criteria
- Able to consent for themselves
- Over 18 and less than 65 years of age
- Able to understand the process of the study
- Fluent in English
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria
- Contraindications to research MRI scanning (including certain metal foreign bodies, pregnancy, severe claustrophobia, etc…)

- Developmental and Epileptic Encephalopathies (DEE)
- Moderate or severe intellectual disability
- Seizures solely due to provoking medical condition, medication, drug or alcohol use
- Age over 65 or under 18 at recruitment.
- Severe, intercurrent or progressive illness likely to EITHER
- Have a prognosis for survival under 24 months

OR

- In the opinion of the investigator will mask the importance to the individual participant of any improvement in their seizures (e.g. severe MS, dementia, etc)

OR

- Which leads to moderate disability requiring help with daily activities (equivalent to modified Rankin Score of 3 or more)

Note that disability solely due to frequency and severity of seizures is NOT an exclusion criterion.

First-ever seizure cohort
- More than one unprovoked seizure ever
- Febrile seizures with the last seizure before 6 years of age are permitted

Newly diagnosed epilepsy cohort
- Treated with ASM for epilepsy for more than 6 months at the time of referral.
- Treatment with ASM for other indications (e.g. neuropathic pain) is NOT an exclusion criteria

Those treated for more than 6 months are no longer “Newly Diagnosed”, although they may qualify as Drug-Resistant in some cases

Drug-resistant epilepsy cohort
- Genetic generalised epilepsy syndromes
- Focal and generalised epilepsy syndromes where the focal seizures are associated with photosensitivity, such as idiopathic photosensitive occipital epilepsy, will not be included.

Other generalised epilepsy syndromes

Healthy Volunteer - Exclusion criteria
- Ever had provoked or unprovoked seizure(s)
- Febrile seizures with the last seizure before 6 years of age are permitted
- Contraindications to research MRI scanning (including certain metal foreign bodies, pregnancy, severe claustrophobia, etc…)
- Moderate or severe intellectual disability
- Age over 65 or under 18 at recruitment.
- Severe, intercurrent or progressive illness likely to EITHER

- Have a prognosis for survival under 24 months

OR

In the opinion of the investigator would have masked the importance to the individual participant of any improvement if included as an epilepsy participant (e.g. severe MS, dementia, etc)

OR

Which leads to moderate disability requiring help with daily activities (equivalent to modified Rankin Score of 3 or more)
- Have a condition that would preclude participation in project activities

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
n/a no intervention and not a randomised trial Study Cohorts are:
- participants with a first unprovoked seizure diagnosis
-participants newly diagnosed with epilepsy
-participants with epilepsy refractory to standard treatments
-Healthy volunteers without epilepsy
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The number of data sets required to be generate a predictive algorithm is thought to be 4000 according to our AI staff. Naturally how this number was determined is proprietary information

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
7/07/2022
Date of last participant enrolment
Anticipated
7/07/2025
Actual
Date of last data collection
Anticipated
6/07/2026
Actual
Sample size
Target
4000
Accrual to date
257
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 311476 0
Government body
Name [1] 311476 0
MRFF (Australian Department of Health
Country [1] 311476 0
Australia
Primary sponsor type
Other
Name
Florey Institute of Neuroscience and Mental Health
Address
Melbourne Brain Centre, 245 Burgundy Street, Heidelberg, Victoria. 3084
Country
Australia
Secondary sponsor category [1] 314343 0
None
Name [1] 314343 0
Address [1] 314343 0
Country [1] 314343 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310940 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 310940 0
Ethics committee country [1] 310940 0
Australia
Date submitted for ethics approval [1] 310940 0
Approval date [1] 310940 0
09/06/2022
Ethics approval number [1] 310940 0
68372

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 119430 0
Prof Graeme Jackson
Address 119430 0
Melbourne Brain Centre
Florey Institute of Neuroscience & Mental Health
245 Burgundy St Heidelberg, Victoria 3084
Country 119430 0
Australia
Phone 119430 0
+61 03 90357068
Fax 119430 0
Email 119430 0
[email protected]
Contact person for public queries
Name 119431 0
Paul Lightfoot
Address 119431 0
Melbourne Brain Centre
Florey Institute of Neuroscience & Mental Health
245 Burgundy St Heidelberg, Victoria 3084
Country 119431 0
Australia
Phone 119431 0
+61 03 90357000
Fax 119431 0
Email 119431 0
[email protected]
Contact person for scientific queries
Name 119432 0
Paul Lightfoot
Address 119432 0
Melbourne Brain Centre
Florey Institute of Neuroscience & Mental Health
245 Burgundy St Heidelberg, Victoria 3084
Country 119432 0
Australia
Phone 119432 0
+61 03 90357000
Fax 119432 0
Email 119432 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.