Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12621001750875
Ethics application status
Approved
Date submitted
22/11/2021
Date registered
21/12/2021
Date last updated
21/12/2021
Date data sharing statement initially provided
21/12/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Autoimmune Encephalitis and Other Neuroinflammatory Conditions in an Australian population
Scientific title
Autoimmune Encephalitis - a rare and debilitating neurological illness affecting the Australian population. A study by the Australian Autoimmune Encephalitis Consortium.
Secondary ID [1] 304401 0
None
Universal Trial Number (UTN)
Trial acronym
AEONC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neuroinflammatory conditions 322210 0
Neurosarcoidosis 324623 0
Cerebral vasculitis 324624 0
Neuromyelitis optica spectrum disorders 324625 0
Acute demyelinating encephalomyelitis 324626 0
Autoimmune seizures 324627 0
new onset refractory status epilepticus 324628 0
CNS lupus 324629 0
Susacs 324630 0
Condition category
Condition code
Neurological 319907 319907 0 0
Other neurological disorders
Inflammatory and Immune System 319908 319908 0 0
Autoimmune diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
In order to enhance our knowledge of Autoimmune Encephalitis and its subtypes and to improve treatment and prognostication we are studying patients with possible autoimmune encephalitis, those with confirmed autoimmune encephalitis and those with other rare neuroinflammatory conditions.
We are reviewing patient medical history treatment and outcomes, imaging, biochemical markers, seizure activity.
Patients will be asked for up three blood samples (6 months or more apart). Neuropsychological assessment completed with our research neuropsychologist, this can take up to 2 hours, . Patients and their caregiver are asked to complete a quality of life questionnaire (NEUROQOL, BRIEF-A, SPECTRA, Care giver burden scale) every 6 months until 3.5 years post enrolment,patients can opt out of questionnaires at any time, questionnaires take about 20 minutes to complete.
Intervention code [1] 320767 0
Not applicable
Comparator / control treatment
Healthy Volunteers will be asked for one blood sample to analyse biomarkers. Neuropsychological assessment completed with our research neuropsychologist, this can take up to 2 hours.
Control group
Active

Outcomes
Primary outcome [1] 327776 0
Characterize the various clinical features, EEG, biochemical, haematological and radiological abnormalities associated with autoimmune encephalitis. Outcome to be assessed by review of medical records, serum assays, EEGs, and MRI.
Timepoint [1] 327776 0
Primary Timepoint (at time of recruitment); secondary timepoint (3 to 6 months after recruitment)
Primary outcome [2] 327781 0
Characterize the central and peripheral immune 'signature' that is associated with autoimmune encephalitis. This will be done by comparing serum assays of patients.
Timepoint [2] 327781 0
Primary Timepoint (T0 - at time of recruitment); secondary timepoint (3 to 6 months after recruitment)
Secondary outcome [1] 396551 0
Characterise the neurocognitive profiles associated with autoimmune encephalitis in both the both acute and post-treatment phases. Outcome to be assessed by neuropsychological assessments.
Timepoint [1] 396551 0
At time of recruitment; and at 6 months, 12 months, 18 months, 24months, 30 months, 36months post recruitment
Secondary outcome [2] 396552 0
Characterise psychopathology associated with autoimmune encephalitis from a patient perspective, this is will be assessed using study specific questionnaire as well as one-on-one assessments with research neuropsychologist.
Timepoint [2] 396552 0
At time of recruitment; and at 6 months, 12 months, 18 months, 24months, 30 months, 36months post recruitment
Secondary outcome [3] 396553 0
Characterise patients psychopathology from a caretakers perspective, this is will be assessed using study specific questionnaire as well as one-on-one assessments with research neuropsychologist.
Timepoint [3] 396553 0
At time of recruitment; and at 6 months, 12 months, 18 months, 24months, 30 months, 36months post recruitment
Secondary outcome [4] 403231 0
Describe the distinctive oculomotor patterns that are seen in patients with autoimmune encephalitis. Horizontal displacement of the eye will be recorded using an Eyelink 1000 dark pupil, video-oculography system.
Timepoint [4] 403231 0
At time of recruitment and a secondary time point more than 1 month later (to a maximum of 12 months after recruitment).
Secondary outcome [5] 404034 0
Characterise subjective cognitive difficulties associated with autoimmune encephalitis from a patient perspective, this is will be assessed using study specific questionnaire as well as one-on-one assessments with research neuropsychologist.
Timepoint [5] 404034 0
At time of recruitment; and at 6 months, 12 months, 18 months, 24months, 30 months, 36months post recruitment
Secondary outcome [6] 404035 0
Characterise quality of life associated with autoimmune encephalitis from a patient perspective, this is will be assessed using study specific questionnaire as well as one-on-one assessments with research neuropsychologist.
Timepoint [6] 404035 0
At time of recruitment; and at 6 months, 12 months, 18 months, 24months, 30 months, 36months post recruitment
Secondary outcome [7] 404036 0
Characterise subjective cognitive difficulties associated with autoimmune encephalitis from a caretakers perspective, this is will be assessed using study specific questionnaire as well as one-on-one assessments with research neuropsychologist.
Timepoint [7] 404036 0
At time of recruitment; and at 6 months, 12 months, 18 months, 24months, 30 months, 36months post recruitment
Secondary outcome [8] 404037 0
Clarifying levels of caretaker burden associated with autoimmune encephalitis from a caretakers perspective, this is will be assessed using study specific questionnaire as well as one-on-one assessments with research neuropsychologist.
Timepoint [8] 404037 0
At time of recruitment; and at 6 months, 12 months, 18 months, 24months, 30 months, 36months post recruitment

Eligibility
Key inclusion criteria
* Confirmed or Antibody Positive Autoimmune Encephalitis:

* Possible Autoimmune Encephalitis:
Diagnosis can be made when all three of the following criteria have been met (Grause et al, 2016 criteria):
- Subacute onset (rapid progression of less than 3 months) of working memory deficits (short-term memory loss), altered mental status, or psychiatric symptoms
- At least one of the following:
* New focal CNS findings
* Seizures not explained by a previously known seizure disorder
* CSF pleocytosis (white blood cell count of more than five cells per mm3)
* MRI features suggestive of encephalitis
- Reasonable exclusion of alternative causes

* Other Neuroinflammatory Brain Conditions (ideally prior to steroid commencement)
- Neurosarcoidosis (with CNS involvement in setting of systemic sarcoid, or biopspy proven neurosarcoidosis)
- Cerebral vasculitis (that is biopsy proven)
- Neuromyelitis optica spectrum disorders
(anti aquaporin 4 or anti MOG positive disorders, or meeting the 2016 diagnostic clinical diagnostic criteria of NMO SD) with concomitant encephalitis / decreased conscious state or cognitive deficits
- Acute demyelinating encephalomyelitis
- Autoimmune seizures / possible autoimmune epilepsy / new onset refractory status epilepticus (NORSE)
- CNS lupus (with systemic and hematologic abnormalities diagnostic of lupus) and other neuroinflammatory brain conditions
- Susacs
- Or Other neuroinflammatory conditions - discuss with central coordinator / CPI

* Healthy Volunteer
- Generally well
- not suffering from an autoimmune condition or other neurological condition
- no evidence of infection in the last two weeks
- not currently being treated with steroids
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Infective encephalitis

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
14/02/2019
Date of last participant enrolment
Anticipated
1/05/2024
Actual
Date of last data collection
Anticipated
31/05/2025
Actual
Sample size
Target
240
Accrual to date
60
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC
Recruitment hospital [1] 21156 0
The Alfred - Melbourne
Recruitment hospital [2] 21157 0
Box Hill Hospital - Box Hill
Recruitment hospital [3] 21160 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [4] 21161 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [5] 21162 0
Concord Repatriation Hospital - Concord
Recruitment hospital [6] 21163 0
Frankston Hospital - Frankston
Recruitment hospital [7] 21164 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [8] 21165 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [9] 21166 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [10] 21167 0
Gold Coast University Hospital - Southport
Recruitment hospital [11] 21168 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [12] 21169 0
Royal Hobart Hospital - Hobart
Recruitment postcode(s) [1] 36016 0
3004 - Melbourne
Recruitment postcode(s) [2] 36017 0
3128 - Box Hill
Recruitment postcode(s) [3] 36020 0
3050 - Parkville
Recruitment postcode(s) [4] 36021 0
3168 - Clayton
Recruitment postcode(s) [5] 36022 0
2139 - Concord
Recruitment postcode(s) [6] 36023 0
3199 - Frankston
Recruitment postcode(s) [7] 36024 0
3084 - Heidelberg
Recruitment postcode(s) [8] 36025 0
3065 - Fitzroy
Recruitment postcode(s) [9] 36026 0
4102 - Woolloongabba
Recruitment postcode(s) [10] 36027 0
4215 - Southport
Recruitment postcode(s) [11] 36028 0
4575 - Birtinya
Recruitment postcode(s) [12] 36029 0
7000 - Hobart

Funding & Sponsors
Funding source category [1] 308770 0
Government body
Name [1] 308770 0
NHMRC
Country [1] 308770 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Level 6, Alfred Centre, 55 Commercial Road, Melbourne 3004
Victoria
Country
Australia
Secondary sponsor category [1] 309675 0
None
Name [1] 309675 0
Address [1] 309675 0
Country [1] 309675 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308685 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 308685 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 308685 0
Australia
Date submitted for ethics approval [1] 308685 0
15/05/2018
Approval date [1] 308685 0
05/10/2018
Ethics approval number [1] 308685 0
HREC/17/Alfred/168

Summary
Brief summary
The project is funded by the NHMRC Medical Research Future Fund to conduct a retrospective and prospective trial of patients with autoimmune encephalitis to gain a better understanding of disease mechanisms, clinical manifestations, identify improved biomarkers for accurate diagnosis, improve treatment options and ultimately enhance patient outcomes/quality of life.
Dr Monif believes that the trial and the creation of the Australian Autoimmune Encephalitis Consortium will raise the profile of the disease so that anyone presenting with the symptoms of autoimmune encephalitis are triaged accordingly, and with timely investigations, the disease is diagnosed promptly. The findings from the national research study are hoped to lead to production of clinical guidelines to assist with early diagnosis and improved treatment options. The ultimate aim is to improve patient outcomes.
Trial website
https://www.monash.edu/medicine/autoimmune-encephalitis/home
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 111550 0
Dr Mastura Monif
Address 111550 0
Monash University/Alfred Health
Level 6, Alfred Centre
99 Commercial Road
Melbourne, 3004
Victoria
Country 111550 0
Australia
Phone 111550 0
+61 3 99030628
Fax 111550 0
Email 111550 0
[email protected]
Contact person for public queries
Name 111551 0
Mrs Tiffany Rushen
Address 111551 0
Monash University/Alfred Health
Level 6, Alfred Centre
99 Commercial Road
Melbourne, 3004
Victoria
Country 111551 0
Australia
Phone 111551 0
+61 3 99038747
Fax 111551 0
Email 111551 0
[email protected]
Contact person for scientific queries
Name 111552 0
Dr Mastura Monif
Address 111552 0
Monash University/Alfred Health
Level 6, Alfred Centre
99 Commercial Road
Melbourne, 3004
Victoria
Country 111552 0
Australia
Phone 111552 0
+61 3 99038747
Fax 111552 0
Email 111552 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.