Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001323819
Ethics application status
Approved
Date submitted
10/08/2021
Date registered
29/09/2021
Date last updated
29/09/2021
Date data sharing statement initially provided
29/09/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Identifying the ideal location for Deep Brain Stimulation (DBS) in the Treatment of Parkinson's Disease.
Scientific title
A multi-centre, prospective trial exploring the use of neuronal signals to identify the ideal location to implant and apply Deep Brain Stimulation (DBS) in the Treatment of Parkinson’s Disease.
Secondary ID [1] 304843 0
Nil
Universal Trial Number (UTN)
U1111-1268-5579
Trial acronym
ADEPT DBS (Assisted Determination of Electrode Positioning and Therapy for Deep Brain Stimulation)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parkinson's disease 322873 0
Condition category
Condition code
Neurological 320451 320451 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants undergoing DBS for Parkinson’s disease will have bioelectric signals (including ERNA) recorded during surgery at the time of DBS lead implantation. The bioelectric signals will be measured using the Bionics Institute customised neurostimulator and recording system (ADEPT). The customised device will be operated by a highly trained researcher from the Bionics Institute. The collection of this bioelectric signal data will occur during the DBS surgery and take approximately 15-20 minutes. The surgeon will not be blinded to the ERNA signal data intra-operatively. However, this ERNA signal data will not be used to guide electrode placement. Except for the recording of bioelectric signals using the ADEPT device, the DBS implantation surgery will proceed as per standard of care. The DBS procedure may vary according to the preferences of the treating team. The final DBS lead location will be determined as per standard of care using a combination of brain imaging guided stereotactic surgery +/- intra-operative clinical evaluation +/- brain microelectrode recordings on a commercially available recording device. The total duration of surgery varies between treating teams, though it is routinely 3 – 5 hours.

All participants will have standard of care brain imaging (MRI brain, CT brain) prior to and after surgery, to identify the location of the DBS electrodes implanted into the brain. All participants will also have an additional (non-standard of care) cranial x-ray within 2 weeks of the first post-operative study visit, 4 months after surgery. The DBS electrodes (standard of care) implanted during surgery have directionality to enable steering of stimulation in a certain direction. This cranial x-ray is required to confirm the directionality of the DBS leads relative to the adjacent anatomical structures. This will enable ERNA signals recorded on each electrode to be accurately referenced to the anatomical location of the electrode.

All participants will have a baseline visit prior to DBS surgery and follow-up study visits at 4 months and 12 months after surgery. At these visits, observational data including motor scores, questionnaires (to measure motor, cognitive and neuropsychiatric outcomes) and the medications and DBS parameters prescribed by the treating doctor will be collected.

A subset of participants will attend an Acute Clinical Evaluation experimental session over two days, 4 months after DBS surgery. Participants for the Acute Clinical Evaluation study will need to meet the additional inclusion criteria of an upper limb rigidity score of equal or greater than 2 on the worse affected side, as rated by the Unified Parkinson’s Disease Rating Scale part III. General circumstances including a good post-operative recovery, geographical location and ease of access to sessions will be considered when selecting participants for this sub-study. During these sessions, the DBS will be adjusted temporarily by a movement disorders clinician with the resultant changes in motor symptoms measured. The participant's DBS parameters will be returned to those prescribed by the treating doctor at the end of the experimental session.
Intervention code [1] 321179 0
Treatment: Devices
Intervention code [2] 321228 0
Treatment: Surgery
Comparator / control treatment
There is no control group in this study. All participants will have the study intervention of the recording of ERNA signals during DBS surgery.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328337 0
Proportion of hemispheres recording ERNA with electrodes positioned within the visualised boundaries of the subthalamic nucleus. The location of the DBS leads recording ERNA relative to the subthalamic nucleus will be identified using a composite of of imaging modalities including MRI Brain, CT Brain and cranial X-ray. The cranial X-ray will confirm the direction of the DBS leads relative to the adjacent anatomical structures as defined by the MRI and CT Brain.


Timepoint [1] 328337 0
ERNA signals will be measured from the investigational ADEPT device during DBS surgery. Routine brain imaging will be collected prior to surgery (MRI Brain), and after DBS surgery, during the inpatient admission (CT Brain). An additional cranial X-ray will be obtained within 2 weeks of the 4-month post-operative study visit.
Primary outcome [2] 328339 0
Adverse events prior to, during and after the ERNA signal recordings at the time of DBS surgery will be collected. The data will be collected retrospectively from the medical records or through patient history at the time of the study visits. This outcome measure exemplifies safety reporting.
Timepoint [2] 328339 0
Adverse event reporting will be collected at 4 times points:
1) Within 4 months prior to DBS surgery
2) During the DBS surgery admission (primary timepoint)
3) At the 4 month post DBS surgery study visit
4) At the 12 month post DBS surgery study visit
Secondary outcome [1] 398638 0
The proximity of the ERNA recording site to the visible boundaries of the subthalamic nucleus (STN) and to an anatomical location nominated as being ‘ideal’ for the application of STN DBS. A composite of imaging modalities including MRI Brain, CT Brain and cranial X-ray will be used to identify the STN, the ideal location to apply STN DBS and the location and directionality of the DBS leads.
Timepoint [1] 398638 0
Routine brain imaging will be collected prior to surgery (MRI Brain), and after DBS surgery, during the inpatient admission (CT Brain). An additional cranial X-ray will be obtained within 2 weeks of the 4 month post-operative study visit.
Secondary outcome [2] 398639 0
DBS programming location chosen by the clinician for chronic therapy (i.e., Standard of Care).
Timepoint [2] 398639 0
DBS programming data prescribed by the clinician will be collected at 4 months and 12 months after DBS surgery.
Secondary outcome [3] 398640 0
Change in motor rating scales with DBS acutely applied at different locations along the implanted lead as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) part III. The locations that DBS is acutely applied will be determined by 1) the research clinician acutely during a DBS titration session, 2) the treating clinician with the DBS location determined chronically at routine clinic appointments over time and 3) the intra-operative ERNA results. This outcome is relevant to the subset of participants enrolled in the Acute Clinical Evaluation study. The DBS will be adjusted temporarily by the research clinician and the resultant changes in symptoms will be recorded on study-specific forms or entered directly into a study-specific Electronic Data Capture system.
Timepoint [3] 398640 0
The Acute Clinical Evaluation Study will occur 4 months after DBS surgery.
Secondary outcome [4] 400571 0
Change in motor rating scales with DBS programming location chosen by the clinician for chronic therapy as measured by the UPDRS part III from baseline compared to after DBS surgery.
Timepoint [4] 400571 0
Motor rating scales will be recorded off DBS at the baseline visit (prior to DBS surgery) and on DBS, with programming chosen by the clinician (using Standard of Care methods) at the 4 month and 12 month post-operative study visits.

Eligibility
Key inclusion criteria
Participants are eligible to be included in the study only if all the following criteria apply:

Participants aged 18 years or older at the time of recruitment into the study.
Participants who have been diagnosed with Parkinson’s disease by a neurologist.
Participants who have planned to have deep brain stimulation surgery for treatment of Parkinson’s disease.
A level of general anaesthesia optimised for neuronal signal recordings, at the discretion of the anaesthetist, at the time of data acquisition during deep brain stimulation surgery.
Participants have a >40% improvement in UPDRS part III motor scores on medication compared to off medication.
Participants who are capable of giving signed informed consent as described the Study Protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).
Participants who can complete regular study visits in accordance with the study protocol requirements.

Participants are eligible for the Acute Clinical Evaluation sub-study if they satisfy:

In the worse affected hemibody off medication, participants who have a minimum upper limb rigidity score of grade 2 on the Unified Parkinson's Disease Rating Scale part III motor scale
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants are excluded from the study if any of the following criteria apply:

Participants who are non-fluent in the English language.
Participants who are unable to give informed consent.
Participants who are pregnant or breastfeeding.
Participants who have a significant psychiatric, behavioural or any other issue which, in the opinion of the investigators, might significantly compromise their ability to understand or complete the study protocol.

Study design
Purpose of the study
Treatment
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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Single group
Other design features
The treating clinician performing standard of care DBS programming and the movement disorders clinician performing the Acute Clinical Evaluation Study and collecting observational data will be blinded to the ERNA signals recorded during DBS surgery. The surgeon will not be blinded to the ERNA signal data during DBS surgery, though this data will not be used to guide DBS lead implantation.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The primary objective of this study is to establish that in patients with Parkinson’s disease, ERNA is safely and reliably recordable from DBS electrodes implanted into the subthalamic nucleus (STN). The reliability of recording ERNA from DBS electrodes will be presented as the proportion of hemispheres where ERNA is recorded from electrodes positioned within the visualised boundaries of the STN on post-operative imaging. The safety of recording ERNA from DBS electrodes will be presented descriptively as the occurrence of adverse events.

The secondary objectives of this study are:
1) To assess the utility of ERNA to identify the ‘ideal’ anatomical location to implant DBS. The relationship between the ERNA signal and the proximity of the ERNA recording site to the visible boundaries of the STN and to an anatomical location nominated as being ‘ideal’ for the application of STN DBS will be evaluated.

2) To compare the utility of ERNA to identify the ‘ideal’ location to program DBS with anatomy and other bioelectric signals. The relationship between the ‘ideal’ location to program DBS identified by ERNA, anatomy and other bioelectric signals and the DBS programming location chosen by the clinician for chronic therapy at 4 and 12 months after DBS surgery will be reported descriptively and compared.

3) To compare the utility of ERNA to identify the ‘ideal’ location to program DBS with standard clinical programming. The change in motor rating scales (Unified Parkinson's Disease Motor Scale part III) with DBS acutely applied at different locations along the implanted lead as identified by ERNA and standard clinical programming (with the location chosen after acute adjustments or chosen by the treating clinician for chronic therapy), will be analysed using group comparison statistics such as mixed effects models.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
11/10/2021
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 20061 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [2] 20062 0
St Vincent's Private Hospital - Fitzroy
Recruitment hospital [3] 20063 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [4] 20064 0
Cabrini Hospital - Malvern - Malvern
Recruitment postcode(s) [1] 34767 0
3065 - Fitzroy
Recruitment postcode(s) [2] 34768 0
3084 - Heidelberg
Recruitment postcode(s) [3] 34769 0
3144 - Malvern
Recruitment outside Australia
Country [1] 23998 0
United Kingdom
State/province [1] 23998 0

Funding & Sponsors
Funding source category [1] 309178 0
Government body
Name [1] 309178 0
Victorian Government - Victorian Medical Research Acceleration Fund
Country [1] 309178 0
Australia
Funding source category [2] 309219 0
Government body
Name [2] 309219 0
National Health and Medical Research Council
Country [2] 309219 0
Australia
Funding source category [3] 309220 0
Commercial sector/Industry
Name [3] 309220 0
Deep Brain Stimulation Technologies Pty Ltd
Country [3] 309220 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Bionics Institute
Address
384-388 Albert St, East Melbourne VIC 3002
Country
Australia
Secondary sponsor category [1] 310362 0
None
Name [1] 310362 0
Address [1] 310362 0
Country [1] 310362 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309037 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 309037 0
Ethics committee country [1] 309037 0
Australia
Date submitted for ethics approval [1] 309037 0
06/07/2021
Approval date [1] 309037 0
07/09/2021
Ethics approval number [1] 309037 0
HREC 154/21

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

Contacts
Principal investigator
Name 112738 0
A/Prof Wesley Thevathasan
Address 112738 0
Bionics Institute
384-388 Albert St,
East Melbourne
VIC 3002
Country 112738 0
Australia
Phone 112738 0
+61 3 9079 1880
Fax 112738 0
Email 112738 0
[email protected]
Contact person for public queries
Name 112739 0
Hugh McDermott
Address 112739 0
Bionics Institute
384-388 Albert St,
East Melbourne
VIC 3002
Country 112739 0
Australia
Phone 112739 0
+61 3 9667 7500
Fax 112739 0
Email 112739 0
[email protected]
Contact person for scientific queries
Name 112740 0
Hugh McDermott
Address 112740 0
Bionics Institute
384-388 Albert St,
East Melbourne
VIC 3002
Country 112740 0
Australia
Phone 112740 0
+61 3 9667 7500
Fax 112740 0
Email 112740 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.