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Trial registered on ANZCTR


Registration number
ACTRN12619001587190
Ethics application status
Approved
Date submitted
26/08/2019
Date registered
19/11/2019
Date last updated
19/11/2019
Date data sharing statement initially provided
19/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety assessment of a sub-scalp electroencephalography monitor
Scientific title
A prospective study to assess the safety of a sub-scalp monitoring device for the recording of brain electrical activity associated with the occurrence of epileptic seizures
Secondary ID [1] 299109 0
Nil known
Universal Trial Number (UTN)
U1111-1239-1830
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 314159 0
Condition category
Condition code
Neurological 312529 312529 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Epileptic seizures recorded by a sub-scalp EEG monitor over 6 months.

The Minder system (an investigational device) includes the following components:
-An implanted electrode lead (IEL) and an implant telemetry unit (ITU) – called the Minder Implant that records two channels of EEG activity from the IEL positioned under the scalp.
-An external behind the ear (BTE) processor – called the Minder BTE that can communicate to a nearby paired mobile phone.
-A custom mobile phone application – called the Minder App installed on a mobile phone that permits the Minder BTE to communicate the captured EEG data from the Minder implant to the phone and ultimately to a secure cloud (known as the Minder cloud).

The captured EEG from the Minder cloud can then be reviewed by trained clinical staff to detect seizures. The Minder App also captures the audio and accelerometer from the phone’s hardware and sends this to the Minder cloud.

The Minder system is designed for collection of EEG data from people with epilepsy, day and night (24/7). This 24/7 collection of EEG data should allow clinicians to review EEG data during seizures.

The purpose of this research is to evaluate the long-term safety of the Minder sub-scalp EEG monitoring system in patients with focal or generalised epilepsy. The device will be implanted in each participant over 6 months.

Each participant will have to undergo general anaesthestic surgery to have the Minder system implanted by a neurosurgeon.

Participants will be trained to maintain the Minder system and have to keep a seizure diary (family/carers may help with this). Participants will also need to attend regular study visits.

The participants can contact the study doctors by phone if they have any concerns. The study coordinator will communicate with participants by phone on a regular basis to arrange study visit appointments and check up on the participants.

At the end of the 6-month implant validation period, each participant will have to undergo another general anaesthetic surgery for a neurosurgeon remove the device.
Intervention code [1] 315377 0
Diagnosis / Prognosis
Comparator / control treatment
No control group for the primary objective of safety assessment of the device and its associated implantation and explantation procedures. All participants are receiving the intervention (i.e., Minder implant device) and there is no sham group of participants that would act as a comparator.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 321172 0
Safety assessment of the device and its associated implantation and explantation procedures.

Adverse event related to device will be used to assess the safety of the device.

Adverse event reporting, including retention from date of implantation throughout the 6-month study and finally to the follow-up evaluation 1-month post explant. In addition to subject/Investigator reported adverse events, a standard physical examination and visual and physical examination of the electrode and implant site will be used by study clinicians to aid in the detection of adverse events.

The case report form has a 'complications form" for each study visit (including surgeries, follow-up visits and in-patient video EEG monitoring) that queries whether an adverse event has occurred. If an adverse event has occurred, the study doctor will need to fill in an adverse event report.

The participants can contact the study doctors by phone if they have any concerns. The study coordinator will communicate with participants by phone on a regular basis to arrange study visit appointments and check up on the participants.

Anticipated side effects include the following:
-Infection related to the device.
-Headaches related to the either insertion or removal surgery.
-Procedural pain and tenderness around the site of implant.
-Effects from the anaesthesia.

Additional side effects may include the following:
-Haematoma.
-Wound haemorrhage.
-Infections are separated into two categories:
-Specific, such as superficial wound, meningitis, encephalitis, cerebral abscess and osteomyelitis.
-General, such as chest infection.
-Procedural and device related injuries.
-Soft tissue injury, including contusion (bruising).
-Implant site reactions.
-Cerebral-Spinal Fluid (CSF) collection.
-Suture rupture and/or wound breakage.
-Twiddler’s syndrome, when the subject “twiddle” or attempt to move the device under the skin, potentially causing device damage and/or injury.
-Device retention/explantation difficulty.
-Erosion of implantable device.
The adverse effects with the highest chance of occurring are device related infection, procedural headache, medical device pain and anaesthetic complications.

There will always be isolated cases where early removal of the implanted device is required. This could be due to infection, pain or even discomfort, but this needs to be looked at on a risk/benefit ratio. It is anticipated that the need for early removal will be low.

Timepoint [1] 321172 0
From date of implantation throughout the 6-month study and finally to the follow-up evaluation 1-month post explant.

The following are the scheduled study dates:
-Day of implant and post-operative check-up the next day after implant (before discharge)
-Week-2 check-up
-Week-4 in-patient video EEG
-Week 8 check-up
-Week-12 in-patient video EEG
-Week-18 check-up
-Week-24 in-patient video EEG and 6-month removal of device (these will be scheduled so that the latter follows immediately after the former, unless there are scheduling issues at the hospital).
-7-month post-removal check-up.

Note that either or both of the week-12 and/or week-24 in-patient video EEG may be may be omitted if the clinical team decides that sufficient epileptiform activity have been captured from the subject.

In addition, participants, study doctors and study coordinator will communicate regularly by phone in between hospital visits.
Secondary outcome [1] 374182 0
Comparison of sub-scalp EEG against seizure diary.

Compare the seizures identified by Epileptologists reviewing the sub-scalp EEG against patient seizure diaries (current clinical practice for counting seizures).

The number of seizures identified is the assessment parameter.. It is anticipated that the two modalities will not correlate well as it has been shown in the literature. Specifically, patient self-reporting of seizures is not reliable.
Timepoint [1] 374182 0
This qualitative comparison will be over 3-months after the device is switched on and recording. The comparison period may be extended to the full 6-months if the clinical team decides that more epileptiform activity need to be captured from the participant(s).
Secondary outcome [2] 374183 0
Comparison of sub-scalp EEG signal against scalp EEG signal.

Compare the EEG signal collected from the Minder implant against scalp EEG electrodes positioned as close to the implanted sub-scalp electrodes as practically feasible. Comparison will be performed by Epileptologists review and spectral analysis of representative EEG data during activities including rest, closed eyes, jaw clenching, eye blinking, eye movements, arithmetic mental exercise, jumping on the spot, tooth brushing, eating and possibly others.

No health outcome is being measured using this assessment. This outcome was included based on communications with the Food and Drugs Administration (FDA, United States of America). It was recommended that in order to demonstrate effectiveness of the Minder implant we need to utilise similarly positioned and limited (i.e., only two bipolar pairs) electrodes placed on the scalp and record with a clinical EEG system as the comparator.
Timepoint [2] 374183 0
Data is collected during week-long in-patient video EEG monitoring. The first monitoring week will be scheduled 4 weeks after implantation. The last monitoring week will be scheduled immediately before device explantation 6 months after implantation.
Secondary outcome [3] 374184 0
Comparison of sub-scalp EEG against the gold standard of video and international 10-20 EEG.

Compare the seizures identified by Epileptologists reviewing the sub-scalp EEG against the gold standard of video and international 10-20 scalp EEG monitoring. There will be up to 3 inpatient video-EEG sessions. The first week-long in-patient video and EEG monitoring will be conducted after the participants recover from the implantation surgery, approximately 4-weeks post-implantation. The week-long monitoring will be repeated at weeks 12 and 24 but (either or both) may be skipped if the clinical team decides that sufficient epileptiform activities have been captured from the participant(s). Patients will also be asked to keep their seizure diaries during the in-patient monitoring, so that all
three modalities in seizure count evaluation can be compared.

The number of seizure identified is the assessment parameter.
Timepoint [3] 374184 0
Data is collected during week-long in-patient video EEG monitoring. The first monitoring week will be scheduled 4 weeks after implantation. The last monitoring week will be scheduled immediately before device explantation 6 months after implantation.
Secondary outcome [4] 374186 0
Evaluation of surgical technique and tools.

This is a composite secondary outcome.

Questionnaire to obtain feedback from surgeon to further improve surgical technique and surgical tool designs.

The questionnaire was designed specifically for this study and is titled:
C1008 Surgical Questionnaire for
Clinical Protocol: A PROSPECTIVE STUDY TO ASSESS THE SAFETY OF A SUB-SCALP MONITORING DEVICE FOR THE RECORDING OF BRAIN ELECTRICAL ACTIVITY ASSOCIATED WITH THE OCCURRENCE OF EPILEPTIC SEIZURES (C1000)

Feedback will be sought from the surgeon to address patient specific variability and learning effects. For example, whether the surgeon encountered any difficulty with measuring the trajectory and using the dummy implant, positioning the bone recess for the implant, using the tunnelling tool, handling the electrode lead and securing excess electrode lead, performing intraoperative testing of the implant and wound closure. If the surgeon encountered any diffulty, we ask the surgeon to provide details.

Surgery duration will also be recorded using a stopwatch by the study team members or theatre staff.
Timepoint [4] 374186 0
The surgeries will be staggered in order to accommodate clinical workflow and availability. This evaluation will be completed when all the scheduled implantation surgeries are completed.
Secondary outcome [5] 374187 0
Evaluation of clinical acceptance and usability.

This is a composite secondary outcome.

Questionnaires for device acceptability and compliance for research participants and clinicians. Specifically, the purpose is to obtain feedback on system design issues including coil on head, comfort, sleeping use, battery charging, data back-up and others. This information will help to upgrade the system design and fine-tune the protocol for Investigation Device Exemption submission to the Food and Drugs Administration.

The questionnaire was designed specifically for this study and is titled:
C1007 Patient Questionnaire for
Clinical Protocol: A PROSPECTIVE STUDY TO ASSESS THE SAFETY OF A SUB-SCALP MONITORING DEVICE FOR THE RECORDING OF BRAIN ELECTRICAL ACTIVITY ASSOCIATED WITH THE OCCURRENCE OF EPILEPTIC SEIZURES (C1000)

Feedback will be sought from the participants to address clinical acceptance and usability. For example, whether the participant felt any discomfort following the implantation, whether recovery from the implantation impacted his/her lifestyle, whether maintaining the Minder system impacted his/her lifestyle, whether there is any issue wearing the Minder system during sleep, feedback regarding recharging/battery life of the Minder system, and whether the participant can recall when he/she has seizures.

We also ask participants to make any suggestions to improve the Minder system.
Timepoint [5] 374187 0
We will obtain feedback from the participants at the completion of the study.
Secondary outcome [6] 374188 0
Evaluation of clinical questionnaires.

This is a composite secondary outcome as per clinical investigation protocol approved by the St. Vincent's Hospital Melbourne Human Research Ethics Committee. The hypothesis is that the subscalp EEG monitor will not have detrimental effects on the patients' well-being.

The clinical accuracy assessments will include the following tests, which will be used to assess each participant's well-being.

Quality of Life in Epilepsy (QOLIE-89), measures quality of life (Devinsky et al. 1995).

Beck Depression Inventory (BDI), measures depression (mood) (Beck et al. 1996)

Beck Anxiety Inventory (BAI), measures anxiety (mood) (Beck et al. 1993)

Multi-dimensional Health Locus of Control (MHLC), measures whether an individual feels their life is internally or externally controlled (Wallston et al. 1978)

Caregiver Burden Inventory (CBI), measures the caregiver burden (Novak et al. 1989)

Liverpool Seizure Severity Scale (LSSS), measures seizure severity (Baker et al. 1991)

Neurological Disorders Depression Inventory for Epilepsy (NDDIE), measures major depression (Gilliam et al. 2006)

A brief measure for assessing Generalized Anxiety Disorder (GAD-7), measure for assessing generalized anxiety disorder (Spitzer et al. 2006)
Timepoint [6] 374188 0
Clinical questionnaires will be evaluated at three time-points. Before implantation, week 4 and at the one-month follow-up post-explant.

Eligibility
Key inclusion criteria
1. Subject is aged between 18 and 75.
2. Subject speaks and reads English.
3. Established clinical diagnosis of focal or generalised epilepsy as defined by the ILAE (International League Against Epilepsy) criteria.
4. A minimum of two clinically identifiable epileptic events per month.
5. Except for epilepsy, subject must be medically and neurologically stable as defined by clinician.
6. An EEG profile consistent with diagnosis of epilepsy.
7. Subject has had prior neuroimaging, within the past 5 years, with report available.
8. Subject can reasonably be expected to maintain a seizure diary and seizure monitoring device alone, or with the assistance of a competent individual.
9. Subject able to complete regular study visits and telephone appointments in accordance with the study protocol requirements.
10. A female subject must have a negative serum pregnancy test within two weeks prior to entering the study, and, if sexually active, must be using a reliable form of birth control, be surgically sterile, or be at least two years post-menopausal.
11. Subjects anatomy will permit implantation of the Minder implant.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subjects with significant progressive disorders or unstable medical conditions requiring acute intervention.
2. Vagus Nerve Stimulation (VNS), Deep Brain Stimulation (DBS), Responsive Neurostimulator System (RNS) or other neurostimulation device implanted for epilepsy or other conditions (e.g. cochlear implants). This is because there is a lack of evidence to confirm that the investigational device and another implanted system will not interfere with one another.
3. Epilepsy surgery within 6 months prior to enrolment
4. Clinically relevant abnormalities in laboratory blood tests detected (e.g. rising or new onset 3x liver function tests (LFTs)).
5. Active suicidal plan/intent in the past 6 months, or a history of suicide attempt in the last 2 years, or more than one lifetime suicide attempt.
6. A serious psychiatric disorder including unstable depression or where changes in pharmacotherapy are needed or anticipated during the study.
7. Any condition that may impact a subject’s ability to follow study procedures or subject’s safety, based on what is known about the trial device.
8. Subject is taking anticoagulants and is unable to discontinue them peri-surgically as required by the neurosurgeon or Investigator.
9. Subject has significant platelet dysfunction from medical conditions or medications (including, particularly, aspirin or clopidogrel). If platelet dysfunction is suspected, subject can be enrolled only if a haematologist, the Investigator, and the neurosurgeon judge it to be advisable.
10. Subject is ineligible for cranial surgery.
11. Subject has a cardiac condition.
12. Pacemaker, implantable cardiac defibrillator or other cardiac management device implanted.
13. Subjects with impaired consent capacity.
14. Subjects on immunosuppression medication.
15. Subjects with localised scalp infection within 6 weeks prior to implantation surgery.
16. Subjects scheduled to have the following contraindicated treatments during the study: Magnetic Resonance Imaging (MRI), Electro-Convulsive Therapy (ECT), lithotripsy and diathermy.
17. Subjects with international travel plans will be excluded from the study. However emergency travel (such as visiting sick relatives overseas) is acceptable.
18. Subjects may be excluded by the study doctors based on their judgement. For example, if the subject is suspected of substance abuse and may jeopardise study participation.

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
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety
Statistical methods / analysis
A sample size of 16 subjects is planned to evaluate the safety of the Minder implant and associated procedures in subjects with focal or generalised epilepsy. To account for dropouts, a total of up to 24 patients may be screened and enrolled in the study to qualify for 16 subjects for implantation. The sample size is not powered to support statistical hypothesis testing but should provide a preliminary indication of safety of the Minder implant and its utility when compared to self-reporting of seizures by patients.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 14617 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 27641 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 303644 0
Commercial sector/Industry
Name [1] 303644 0
Epi-Minder Pty Ltd
Address [1] 303644 0
384-388 Albert St, East Melbourne VIC 3002
Country [1] 303644 0
Australia
Funding source category [2] 303648 0
Government body
Name [2] 303648 0
Department of Health and Human Services (Victoria)/Victorian Medical Research Acceleration Fund
Address [2] 303648 0
Department of Health & Human Services
50 Lonsdale Street
Melbourne, 3000
Victoria, Australia
Country [2] 303648 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Epi-Minder Pty Ltd
Address
384-388 Albert St, East Melbourne VIC 3002
Country
Australia
Secondary sponsor category [1] 303737 0
None
Name [1] 303737 0
Address [1] 303737 0
Country [1] 303737 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304170 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 304170 0
Street address:
Research Governance Unit
Level 5, Building E (Aikenhead Building)
27 Victoria Parade
Fitzroy VIC 3065

Postal address:
Research Governance Unit
St Vincent's Hospital
PO Box 2900
Fitzroy VIC 3065
Ethics committee country [1] 304170 0
Australia
Date submitted for ethics approval [1] 304170 0
20/08/2019
Approval date [1] 304170 0
13/11/2019
Ethics approval number [1] 304170 0

Summary
Brief summary
The research project is to test and validate a new system for monitoring focal or generalised epilepsy. The new monitoring system is called Minder and is comprised of an implanted device that communicates to an external device, mobile phone and secure cloud. These components, known as the Minder system, will record each subject's electroencephalogram (EEG) data, also known as brain waves, and export it to a secure cloud via the mobile phone. The subjects will be required to use this Minder system continuously throughout the study for a period of up to 6 months, during both wake and sleep. The subjects continuous EEG recordings during the study will be downloaded from the secure cloud and reviewed by trained clinical staff to detect seizures.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96034 0
Prof Mark J Cook
Address 96034 0
41 Victoria Parade
St. Vincent's Hospital Melbourne
Fitzroy VIC 3065
Country 96034 0
Australia
Phone 96034 0
+61 3 9231 3068
Fax 96034 0
Email 96034 0
markcook@unimelb.edu.au
Contact person for public queries
Name 96035 0
Dr Alan Lai
Address 96035 0
Department of Medicine at St. Vincent's Hospital Melbourne, The University of Melbourne
Clinical Sciences Building,
Level 4 / 29 Regent Street,
Fitzroy VIC 3065, Australia
Country 96035 0
Australia
Phone 96035 0
+61 3 9231 3296
Fax 96035 0
Email 96035 0
alan.lai@unimelb.edu.au
Contact person for scientific queries
Name 96036 0
Dr Alan Lai
Address 96036 0
Department of Medicine at St. Vincent's Hospital Melbourne, The University of Melbourne
Clinical Sciences Building,
Level 4 / 29 Regent Street,
Fitzroy VIC 3065, Australia
Country 96036 0
Australia
Phone 96036 0
+61 3 9231 3296
Fax 96036 0
Email 96036 0
alan.lai@unimelb.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Epi-Minder Pty Ltd prefers to keep all data private except if required by authorities.
What supporting documents are/will be available?
Ethical approval
How or where can supporting documents be obtained?
Type [1] 5741 0
Ethical approval
Citation [1] 5741 0
Link [1] 5741 0
Email [1] 5741 0
Other [1] 5741 0
Summary results
No Results