Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000130763
Ethics application status
Approved
Date submitted
11/11/2021
Date registered
27/01/2022
Date last updated
14/02/2023
Date data sharing statement initially provided
27/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The Liberty Trial: Investigating spinal cord stimulation as a new treatment for spasticity of the legs in children living with cerebral palsy
Scientific title
A prospective feasibility study examining the ability of closed-loop spinal cord stimulation to reduce lower limb spasticity in children living with cerebral palsy: “The Liberty Trial”
Secondary ID [1] 305773 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spasticity 324277 0
Cerebral Palsy 324278 0
Condition category
Condition code
Physical Medicine / Rehabilitation 321771 321771 0 0
Other physical medicine / rehabilitation
Neurological 321996 321996 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention in this trial consists of the implantation of an electronic active medical device, a spinal cord stimulator, known as the Evoke™ Closed Loop Stimulator with implantable leads, is aimed to reduce lower limb spasticity in children living with cerebral palsy (CP).
The implantation surgery usually takes about 1 hour and is performed by a qualified paediatric neurosurgeon under complete anaesthesia.
The participants are followed up for a duration of 2 years with scheduled visits at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months after the implantation surgery. Usage logs and outcome measures are collected at each visit.
Within 7±2 days following device activation, each participant will begin up to 40 hours of Intensive Physiotherapy (IPT) to be completed within 8 weeks of initiating it (duration and number of visits are at the discretion of the participant and their physiotherapist). The physiotherapy will be provided by an accredited physiotherapist and the program will be patient specific according to their identified goals. As such, the physiotherapy program will be tailored to each patient and their goals and patients won’t necessarily share common exercises. A common goal is the ability to dress autonomously and exercises will include movements to help the patients circumvent their spasticity to achieve the desired outcome. Other common goals will be the ability to walk up and down stairs or bend down to pick up objects. The exercise programs will be tailored to help the patients achieve these goals by adapting their movements taking into consideration limitations caused by their spasticity. Their goals and progress will be captured periodically using the COPM and GAS forms and will be evaluated at baseline during the intensive physiotherapy phase and at 3, 6, 12 months after the device implantation.
Intervention code [1] 322171 0
Treatment: Devices
Intervention code [2] 322375 0
Rehabilitation
Comparator / control treatment
No Control Group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 329519 0
The primary outcome of this study is a proportion of participants with a change in the Modified Ashworth Scale (MAS).
Timepoint [1] 329519 0
Baseline, implant, 1, 3, 6 (primary endpoint), 9, 12, 15, 18, 21, 24 months post-device implantation.
Secondary outcome [1] 402847 0
Incidence of adverse events.
The adverse event can be any change, undesired, noxious or pathological in a participant illustrated by signs, symptoms and /or laboratory changes that occur during a clinical trial, whether or not considered drug/treatment related. If adverse experiences occur, the first concern will be the safety of the participant. Appropriate medical intervention will be made. Any device related adverse experiences or complications observed by the investigator or reported by the participants will be recorded in the appropriate section of the participant’s case report forms.
Timepoint [1] 402847 0
Baseline, implant, 1, 3, 6, 9, 12, 15, 18, 21, 24 months post-device implantation
Secondary outcome [2] 402848 0
Changes in muscle tone as measured by the Modified Tardieu Scale (MTS).
Timepoint [2] 402848 0
Baseline, implant, 1, 3, 6, 9, 12, 15, 18, 21, 24 months post-device implantation
Secondary outcome [3] 402849 0
Passive range of motion of hips, knees and ankles as measured by goniometer
Timepoint [3] 402849 0
Baseline, 3, 6, 12, 18, and 24-months post-device implantation
Secondary outcome [4] 402850 0
Gross Motor Function Classification Scale: (GMFCS-Expanded and Revised)
Timepoint [4] 402850 0
Baseline, 3, 6, 12, 18 and 24-months post-device implantation
Secondary outcome [5] 402851 0
Gross Motor Function Measure (GMFM-66)
Timepoint [5] 402851 0
Baseline, 3, 6, 12, 18 and 24-months post-device implantation
Secondary outcome [6] 402852 0
If ambulant: Changes from baseline of functional mobility scale assessed by the Functional Mobility Scale (5m, 50m, 500m),
Timepoint [6] 402852 0
Baseline, 1, 3, 6, 9, 12, 18, and 24 months post-device implantation
Secondary outcome [7] 402853 0
If ambulant: Changes in the Gait Profile Score and the Gait Variable Scores from Gait Analysis (composite)
Timepoint [7] 402853 0
Baseline, 6, 12, and 24-month post-device implantation. Optional assessments at 3, 9, 15, 18 and 21 months post-device implantation.
Secondary outcome [8] 402855 0
If non-ambulant: Changes from baseline of care and comfort, assessed by the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire
Timepoint [8] 402855 0
Baseline, 1, 3, 6, 9, 12, 18, and 24-months post-device implant
Secondary outcome [9] 402857 0
Goal-directed functional performance, assessed by the: Canadian Occupational Performance Measure (COPM)
Timepoint [9] 402857 0
Baseline, weekly during the physiotherapy phase and 3, 6, 12 months post-device implantation
Secondary outcome [10] 402858 0
Global Impression of Change as assessed by the Patient
Timepoint [10] 402858 0
3, 6, 12, 18 and 24-months post-device implantation
Secondary outcome [11] 402859 0
Changes from baseline of pain assessed using the: Faces Pain Scale-Revised
Timepoint [11] 402859 0
Baseline, 3, 6, 12, 18, and 24-months post-device implantation.
Secondary outcome [12] 402861 0
PROMIS Paediatric Sleep Disturbance and Sleep-Related Impairment item banks
Timepoint [12] 402861 0
Baseline, 3, 6, 12, 18, and 24-months post-device implantation
Secondary outcome [13] 402862 0
Cerebral Palsy Quality of Life Questionnaires (CPQOL): Child or Teen Self Report
Timepoint [13] 402862 0
Baseline, 6, 12, 18, and 24-months post-device implantation.
Secondary outcome [14] 402863 0
Changes from baseline of medication use as recorded in the medications log.
Timepoint [14] 402863 0
Baseline, 1, 3, 6, 9, 12, 15, 18, 21, 24-months post-device implantation.
Secondary outcome [15] 403943 0
If ambulant: Changes from baseline of functional mobility scale assessed by the Gillette Functional Assessment Questionnaire,
Timepoint [15] 403943 0
Baseline, 1, 3, 6, 9, 12, 18, and 24 months post-device implantation
Secondary outcome [16] 403944 0
If ambulant: Changes from baseline of functional mobility scale assessed by the 6 minute walk test
Timepoint [16] 403944 0
Baseline, 1, 3, 6, 9, 12, 18, and 24 months post-device implantation
Secondary outcome [17] 403945 0
If ambulant: Changes from baseline of functional mobility scale assessed via Timed up-and-go test
Timepoint [17] 403945 0
Baseline, 1, 3, 6, 9, 12, 18, and 24 months post-device implantation
Secondary outcome [18] 403946 0
Goal-directed performance assessed by the Goal Attainment Scaling (GAS)
Timepoint [18] 403946 0
Baseline, weekly during the physiotherapy phase and 3, 6, 12 months post-device implantation
Secondary outcome [19] 403947 0
Global Impression of Change as assessed by the Caregiver
Timepoint [19] 403947 0
3, 6, 12, 18 and 24-months post-device implantation
Secondary outcome [20] 403948 0
Global Impression of Change as assessed by the Clinician
Timepoint [20] 403948 0
3, 6, 12, 18 and 24-months post-device implantation
Secondary outcome [21] 403949 0
Changes from baseline of pain assessed using the: PROMIS Paediatric Pain Intensity, Quality, Interference and Behaviour item banks
Timepoint [21] 403949 0
Baseline, 3, 6, 12, 18, and 24-months post-device implantation.
Secondary outcome [22] 403950 0
Assessment of pain location from the Body Map-Revised
Timepoint [22] 403950 0
Baseline, 3, 6, 12, 18, and 24-months post-device implantation
Secondary outcome [23] 403951 0
Cerebral Palsy Quality of Life Questionnaires (CPQOL): Primary Caregiver Proxy Report
Timepoint [23] 403951 0
Baseline, 6, 12, 18, and 24-months post-device implantation.

Eligibility
Key inclusion criteria
Individuals who meet the following criteria will be considered potential candidates for this clinical study:

1. Have been diagnosed with spasticity in at least one lower limb muscle group in at least one leg as a result of CP (Modified Ashworth Scale 2 or greater in one muscle group)
2. Have spastic diplegia, hemiplegia or quadriplegia
3. Minimal dyskinesia or ataxia
4. No spinal deformity
5. Have a Gross Motor Function Classification System (GMFCS) level of 2 to 5
6. Have been approved to undergo SCS of the spinal cord and be an appropriate candidate for the surgical procedure required in this study based on the clinical judgment of the Eligibility Advisory Panel
7. Be on a stable dose (no new, discontinued, or changes in dose) of all prescribed pain or spasticity medications for at least 30 days prior to baseline evaluation
8. Subject is between 6 to 16 years of age at the time of consent;
9. Be willing and capable of giving written informed consent, and/or have a parent/guardian who is willing to sign informed consent on their behalf
10. Be willing and able to comply with study-related requirements, procedures, and visits
Minimum age
6 Years
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Individuals who meet any one of the following criteria will be excluded from this clinical study:
1. Show presence of progressive neurological disease
2. Have drug resistant epilepsy (International League Against Epilepsy criteria)
3. Have ever been diagnosed with an immune system disorder or immune deficiency syndrome
4. Require ventilator support
5. Be unwell, or if the participant’s medical condition does not allow safe travel
6. Have had, or are scheduled for, lower limb botulinum-A toxin or surgery affecting the lower limbs within 3 months prior to device activation or 6 months following device activation
7. Have an implanted pacemaker, implanted ITB pump, previous spinal surgery (including SDR) and or any other system that may interfere with the EvokeTM CLS
8. Have a condition currently requiring or likely to require the use of MRI or diathermy
9. Have a life expectancy of less than two years
10. Be allergic, or have shown hypersensitivity, to any materials of the neurostimulation system which come in contact with the body
11. Be concomitantly participating in another clinical study unless pre-approved by Closed Loop Medical
12. Have intellectual disability (diagnosed with a presumed Intellectual Disability as determined by a psychologist with the relevant expertise or having an Intellectual Quotient (IQ) <69 as tested on a standardised measure)

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Treatment will be determined by evaluation at determined time-points using defined performance criteria. Additionally; the patient demographics, diagnosis and prior anti-spasticity treatments, will be tabulated and descriptive statistics will be estimated. These include means (or medians) and standard deviations (or inter-quartile ranges) for continuous or ordinal variables and proportions for categorical variables.

This study is powered conservatively to show a decrease in Modified Ashworth Scale of at least one-point in more than 50% of implanted participants with a 5% confidence level. With an assumed true effect size of 75%, the study is powered to 80% (5% one-sided alpha) with 23 participants, using an exact binomial test. The enrolment number of 30 participants allows us to account for up to 30% attrition.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/07/2023
Actual
Date of last participant enrolment
Anticipated
29/02/2024
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 21084 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 35937 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 310130 0
Commercial sector/Industry
Name [1] 310130 0
Closed Loop Medical Pty Ltd
Country [1] 310130 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Closed Loop Medical Pty Ltd
Address
407 Pacific Highway
Artarmon NSW 2064
Country
Australia
Secondary sponsor category [1] 311442 0
None
Name [1] 311442 0
Address [1] 311442 0
Country [1] 311442 0
Other collaborator category [1] 282068 0
Commercial sector/Industry
Name [1] 282068 0
Cerebral Palsy Alliance
Address [1] 282068 0
187 Allambie Rd
Allambie Heights
NSW 2100
Country [1] 282068 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309818 0
Sydney Children's Hospital Network HREC
Ethics committee address [1] 309818 0
Cnr Hawkesbury Rd & Hainsworth St
Westmead
NSW 2145
Ethics committee country [1] 309818 0
Australia
Date submitted for ethics approval [1] 309818 0
12/07/2021
Approval date [1] 309818 0
25/08/2021
Ethics approval number [1] 309818 0
2019/ETH14021

Summary
Brief summary
There is a need for better treatments for spasticity in cerebral palsy (CP). Spasticity is a common target for many established treatments for CP such as Botulinum toxin A injection, oral baclofen, intrathecal baclofen pump implantation, and selective dorsal rhizotomy surgery. For over 40 years there have been attempts to use spinal cord stimulation (SCS) to treat spasticity, yet its role as a treatment in cerebral palsy has been limited. Recent advances in technology have enabled closed-loop control of SCS devices meaning that targeted electrical stimulation of the spinal cord can now be used in a real world setting with a device that is not adversely affected by sudden movements in posture, such as from muscle spasms. This technological advance combined with evidence relating to the importance of early intervention in cerebral palsy have led to the initiation of this trial.

The Liberty Trial investigates the use of closed loop spinal cord stimulation in the treatment of lower limb spasticity for children living with spasticity. Children between 6 and 16 years with CP and spasticity predominately affecting at least one lower limb and who are candidates for SCS will be enrolled. The total study duration is 36 months. The study enrolment period is expected to be 12 months, and participants implanted with the investigational device will be followed for 24 months from implant. Treatment safety will be investigated, and efficacy will be determined by evaluation of the outcome measures at determined time-points using defined performance criteria. Additionally; the patient demographics, diagnosis and prior anti-spasticity treatments will be documented.

The intervention in this trial consists of the implantation of an electronic medical device, a spinal cord stimulator, known as the EvokeTM Closed Loop Stimulator and leads, to reduce lower limb spasticity in children living with cerebral palsy.

Intensive physiotherapy will accompany the intervention to try to improve lower limb function and mobility. This will be performed face to face by a physiotherapist experienced in post-spasticity intervention rehabilitation (i.e. botulinum toxin and selective dorsal rhizotomy). The principles of Goal Directed Therapy will be followed to compare the ability of the participants to achieve meaningful functional goals before and after the intervention.
Trial website
Trial related presentations / publications
Public notes
This open labelled prospective single armed study is designed to assess the effect of closed loop SCS on spasticity in children living with CP. Primary and secondary outcome measures have been chosen to align to two registry studies. Comparison of the data generated here with the registry studies will allow selection of optimal parameter settings, patient groups and design of a future randomised controlled study. Intensive physiotherapy has been included in the trial design to help to improve in the attainment of functional goals and we have sought to control for its effect by having.

Contacts
Principal investigator
Name 115494 0
Dr Simon Paget
Address 115494 0
The Children’s Hospital at Westmead
Locked Bag 4001
Westmead
NSW 2145
Country 115494 0
Australia
Phone 115494 0
+61298452819
Fax 115494 0
Email 115494 0
simon.paget@health.nsw.gov.au
Contact person for public queries
Name 115495 0
Dr Joe Dusseldorp
Address 115495 0
Concord Hospital
Hospital Rd
Concord
NSW 2139
Country 115495 0
Australia
Phone 115495 0
+61 297675000
Fax 115495 0
+61240440144
Email 115495 0
drjoedusseldorp@icloud.com
Contact person for scientific queries
Name 115496 0
Dr Gerrit Gmel
Address 115496 0
Closed Loop Medical
407 Pacific Highway
Artarmon, NSW 2064
Country 115496 0
Australia
Phone 115496 0
+61284058700
Fax 115496 0
Email 115496 0
gerrit.gmel@saludamedical.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The device under investigation by the trial sponsor is proprietary. Aggregated data will be the subject of publications at multiple timepoints of follow-up.


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.