Acquired Brain Injury (Including Stroke), Centreal Neurological Condition, Multiple Sclerosis, Spinal Cord Injury
Conditions
Keywords
Cryoneurolysis, Spasticity, Pain, Acquired Brain Injury, Stroke, Multiple Sclerosis, Spinal Cord Injury, Central Neurological Condition, Botulinum Toxin (botox), Iovera, Chemodenervation, BoNT-A, Cryoneurotomy, Cryoneurectomy, Cryoanalgesia
Brief summary
Spasticity is an umbrella term for impairments of muscle tone and control in people with damage to the brain and spinal cord. It is highly prevalent and results in pain, stiffness, and contribute to difficulties in activities of daily living. Current treatment options are limited, and many people experience only partial reduction in spasticity and frequent repeated treatments are needed. Cryoneurolysis is a medical technique which involves the controlled freezing of the nerves. It has been approved in the UK for the treatment of pain in the context of spasticity through the targeting of nerves which control problematic muscles. Oxford University Hospitals NHS Foundation Trust has been offering this treatment routinely since January 2024. This pilot study aims to improve the understanding of the potential effectiveness of this treatment and its potential side effects when compared with a more commonly used treatment (Botulinum Toxin). Participants will be randomly allocated to receive usual care with Botulinum Toxin (control group) or usual care with Cryoneurolysis (intervention group). The investigators will assess pain, goal attainment, side effects, spasticity, disability and independence in daily activities, and movement of the arm and leg. Assessments will be at baseline and then 6-, 12-, 18-, and 24-weeks following treatment. Participants who are randomised to the control group will have the opportunity to receive cryoneurolysis treatment after the 12 week follow up assessment. The results of this study will help to guide future studies to examine the effectiveness of this treatment.
Detailed description
Spasticity is an umbrella term for impairments of muscle activity and control in the context of damage or dysfunction in the central nervous system, occurring in up to 87% of spinal cord injury patients, 42% of stroke patients, and 80% of patients with multiple sclerosis. Spasticity results in pain, stiffness, and restrictions to activity including difficulties in personal care and mobility and a significant impact on quality of life. Treatments including oral medications, botulinum toxin injections, and physical therapies can provide some degree of relief, but effectiveness varies widely. Many patients experience only partial reduction in spasticity, contributing to ongoing functional limitations. Botulinum toxin injections provide temporary relief necessitating frequent treatments (every 3-4 months). This is burdensome for patients and healthcare providers, with associated time and treatment costs. Pharmacological treatments can lead to systemic side effects including drowsiness, dizziness, and cognitive impairments. Surgical interventions are resource-intensive and require specialised medical facilities. Their associated costs, in terms of financial resources and healthcare infrastructure, significantly limit access for certain patients. Cryoneurolysis, a novel medical technique, involves the controlled freezing of nerve tissue to temporarily disrupt its function. While primarily used for pain, there is a growing interest in its application for managing spasticity and it is currently approved for the treatment of pain in the context of spasticity at Oxford University Hospitals NHS Trust. Observational studies suggest immediate relaxation of the affected muscles, resulting in improved joint range of motion, enhanced functional mobility, and reduced pain. The investigators' own open-label proof-of-principle clinical data suggest the potential for substantial improvements in the impact of spasticity on quality of life. This pilot randomised controlled study aims to improve the understanding of the potential clinical effectiveness and side effect profile of cryoneurolysis as a treatment for pain in the context of spasticity in people with a range of neurological conditions (e.g. acquired brain injury (ABI), spinal cord injury, stroke, multiple sclerosis).
Interventions
PROCEDURECryoneurolysis
Nerves that require treatment, and the number of treatments required for each nerve will be identified by routine clinical judgement. Nerve targets are identified using an ultrasound machine. The handheld Iovera cryoneurolysis device will be used for treatment. Participants will receive up to 4 treatments of cryoneurolysis for each nerve or nerve branch that requires treatment. It is anticipated that participants will have between 1 and 5 nerves or nerve branches per limb treated. Each Cryoneurolysis treatment takes 110 seconds. Total treatment time will be determined by number of nerves targeted and number of cryoneurolysis treatments per nerve. The shortest duration, with setup, is likely to be 60 minutes and the longest 120 minutes.
PROCEDUREBotulinum toxin
Muscles that require treatment with Botulinum Toxin will be identified by routine clinical assessment. Muscle targets will be identified using an ultrasound machine. It is anticipated that participants will have between 2 and 8 muscles identified for target. The participant will receive up to 200 units of Xeomin (Botulinum Toxin) per muscle that requires treatment. Treatment session of Botulinum Toxin will take 60 to 90 minutes.
Sponsors
University of Oxford
Bournemouth University
Oxford University Hospitals NHS Trust
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Participants randomised to control will be given the opportunity (but are not required) to crossover to the intervention arm at 12-weeks post-treatment. The intervention arm will not crossover to control arm.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant is willing and able to give informed consent for participation in the trial OR a positive opinion from a consultee is provided by a family member or carer (relative or friend) willing to provide personal consultee (PC) advice. * Male or Female, aged 18 years or above. * Diagnosed with a central neurological condition, including acquired brain injury (e.g. from ischaemic stroke, trauma, or haemorrhage), multiple sclerosis, and spinal cord injury. * Clinical indication for Botulinum Toxin and Cryoneurolysis treatment, including pain associated with spasticity and with a clinically meaningful response to diagnostic nerve block to specific nerves or nerve branches that can be treated with cryoneurolysis. * At least one rehabilitation goal related to management of pain resulting from spasticity.
Exclusion criteria
* Participant has received Botulinum toxin or cryoneurolysis within the last 90 days. * Raynaud's syndrome. * Cryoglobulinaemia. * Cold urticaria. * Bleeding disorders. * Localised infection at intended treatment site. * Planned oral antispasmodic medication dose changes. * Pregnancy, breastfeeding, or planning pregnancy in the trial period. * Scheduled elective surgery or other procedures requiring general anaesthesia during the trial. * Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial. * Participants who are currently enrolled in another trial may be excluded if it is deemed (in the investigator's opinion) that participation could influence the results for either study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Goal Attainment Scale | 6-weeks post-treatment | An individualised outcome measure involving goal selection and goal scaling that is standardised in order to calculate the extent to which a patient's goals are met. GAS comprises of goals divided into a 5-point scale of level of expected outcome: from -2 (much less than expected) to +2 (much more than expected). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Goal Attainment Scale | 12-weeks post treatment | An individualised outcome measure involving goal selection and goal scaling that is standardised in order to calculate the extent to which a patient's goals are met. GAS comprises of goals divided into a 5-point scale of level of expected outcome: from -2 (much less than expected) to +2 (much more than expected). |
| Spasticity | 6- and 12-weeks post treatment | Directly assessed by measuring the muscle activity to a passive stretch |
| Range of Motion | 6- and 12-weeks post treatment | Assessed using a goniometer |
| Patient Reported Impact of Spasticity Measure (PRISM) | 6- and 12-weeks post treatment | Questionnaire assessing spasticity related quality of life (41 items that describe impacts of spasticity, each of which is rated on a scale of 0-4 from never true for me to very often true for me). |
| EQ5D | 6- and 12-weeks post treatment | Questionnaire assessing quality of life across 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels which are scored 1 - 5, with higher scores indicating worse outcome. |
| Spasticity Related Quality of Life instrument (SQoL-6D) | 6- and 12-weeks post treatment | Questionnaire assessing spasticity related quality of life (range 0 - 24, higher score indicating worse condition) |
| Barthel Index | 6- and 12-weeks post treatment | Scale measuring a person's ability to complete activities of daily living (range 0 - 100, higher scores indicating more independence) |
| Gait assessment - Walking Speed | 6- and 12-weeks post treatment | Kinematic assessment of lower extremity function, using EMG and motion capture cameras. Walking speed is measured in meters per second (m/s), with slower speed indicating worse outcome. |
| Gait assessment - Gait profile score | 6- and 12-weeks post treatment | Kinematic assessment of lower extremity function using EMG and motion capture cameras. The gait profile score is measured in degrees, with higher scores indicating more abnormality, and no maximum score. |
| Leg Activity Measure (LEG-A) | 6- and 12-weeks post treatment | Questionnaire assessing lower extremity function (3 sections: Section A range: 0-36; Section B range 0-60; Section C range 0 - 36. Higher score indicates more difficulty/severity.) |
| Shriners Hospital Upper Extremity Evaluation (SHUEE) | 6- and 12-weeks post treatment | Kinematic assessment of upper extremity function using motion capture cameras. |
| Arm Activity Measure (ARM-A) | 6- and 12-weeks post treatment | Questionnaire assessing upper extremity function (2 sections: Section A range: 0-32; Section B range 0-52. Higher score indicates more difficulty.) |
| Functional Assessment Test for Upper Limb (FAST-UL) | 6- and 12-weeks post treatment | Assessment of upper extremity function (selected movements assessed and scored between 0 - 3, with higher scores indicating ability to complete movement more fully). |
| Pressure Pain Thresholds (PPT) | 6, 12, 18, and 24 weeks post-treatment | Sensory testing using a manual algometer to assess pain thresholds. |
| Self-reported Pain | 6, 12, 18, and 24 weeks post-treatment | Self-report, as measured by a numerical rating scale (range 0 - 10, higher scores indicating higher pain levels). |
| Douleur Neuropathique en 4 (DN4) | 6, 12, 18, and 24 weeks post-treatment | Questionnaire used to determine whether pain is neuropathic in origin (range 0 - 10; a score of 4 or more suggests the presence of neuropathic pain). |
| Neuropathic Pain Symptom Inventory (NPSI) | 6, 12, 18, and 24 weeks post-treatment | Questionnaire used to quantify neuropathic pain (range 0 - 100, higher scores reflect worse neuropathic pain). |
| Side Effects | 6, 12, 18, and 24 weeks post-treatment | As measured by self-report side effects questionnaire |
| Modified Ashworth Scale | 6- and 12-weeks post treatment | Assessment which requires the researcher to passively move the person's affected limb(s) and assess their resistance to movement (score range 0 - 4, higher score indicating increased in tone). |
| Modified Tardieu Scale | 6- and 12-weeks post treatment | Assessment which requires the researcher to passively move the person's affected limb(s) and assess their resistance to movement (score range 0 - 4, higher score indicating increased resistance). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Goal Attainment Scale | 18- and 24-weeks post-treatment | An individualised outcome measure involving goal selection and goal scaling that is standardised in order to calculate the extent to which a patient's goals are met. GAS comprises of goals divided into a 5-point scale of level of expected outcome: from -2 (much less than expected) to +2 (much more than expected). |
| Modified Ashworth Scale | 18- and 24-weeks post-treatment | Assessment which requires the researcher to passively move the person's affected limb(s) and assess their resistance to movement (score range 0 - 4, higher score indicating increased in tone). |
| Modified Tardieu Scale | 18- and 24-weeks post-treatment | Assessment which requires the researcher to passively move the person's affected limb(s) and assess their resistance to movement (score range 0 - 4, higher score indicating increased resistance). |
| Spasticity | 18- and 24-weeks post-treatment | Directly assessed by measuring the muscle activity to a passive stretch |
| Range of motion | 18- and 24-weeks post-treatment | Assessed using a goniometer |
| Patient Reported Impact of Spasticity Measure (PRISM) | 18- and 24-weeks post-treatment | Questionnaire assessing spasticity related quality of life (41 items that describe impacts of spasticity, each of which is rated on a scale of 0-4 from never true for me to very often true for me) |
| EQ5D | 18- and 24-weeks post-treatment | Questionnaire assessing quality of life across 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels which are scored 1 - 5, with higher scores indicating worse outcome. |
| Spasticity Related Quality of Life instrument (SQoL-6D) | 18- and 24-weeks post-treatment | Questionnaire assessing spasticity related quality of life (range 0 - 24, higher score indicating worse condition) |
| Barthel Index | 18- and 24-weeks post-treatment | Scale measuring a person's ability to complete activities of daily living (range 0 - 100, higher scores indicating more independence) |
| Leg Activity Measure (LEG-A) | 18- and 24-weeks post-treatment | Questionnaire assessing lower extremity function (3 sections: Section A range: 0-36; Section B range 0-60; Section C range 0 - 36. Higher score indicates more difficulty/severity.) |
| Arm Activity Measure (ARM-A) | 18- and 24-weeks post-treatment | Questionnaire assessing upper extremity function (2 sections: Section A range: 0-32; Section B range 0-52. Higher score indicates more difficulty.) |
| Feedback Questionnaire/Interview | 24 weeks post treatment | Qualitative feedback using either a semi-structured interview or a self-reported questionnaire (using the same questions as interview schedule), as per preference of participant, used to explore the satisfaction, experience, and anticipated barriers/facilitators to clinical implementation for the treatments. |
| Sleep Condition Indicator | 6, 12, 18, and 24 weeks post-treatment | Questionnaire assessing self-reported insomnia symptoms (range 0-32, higher numbers indicate less symptoms of insomnia) |
Countries
United Kingdom
Contacts
Primary ContactAnton Pick, MBChB
Backup ContactBarbara Robinson, MSc
Outcome results
None listed