Cryoneurolysis to treat pain in the context of spasticity
| ISRCTN | ISRCTN50433077 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN50433077 |
| Integrated Research Application System (IRAS) | 1011743 |
| Protocol serial number | CTA 21439/0250/001-0001 |
| Protocol serial number | PID18403 |
| Sponsor | Oxford University Hospitals NHS Trust |
| Funder | Pacira BioSciences |
- Submission date
- 09/09/2025
- Registration date
- 09/12/2025
- Last edited
- 09/12/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
Spasticity is an umbrella term for impairments of muscle activity and control in people with damage to the brain and spinal cord. It is common and results in pain, stiffness, limb deformities, and contributes to difficulties in activities of daily living. Current treatment options, such as stretching, splinting, and Botulinum Toxin injections, are limited, many people experience only partial reduction in spasticity and frequent repeated treatments are needed.
Cryoneurolysis is a medical technique which involves the controlled freezing and thawing of 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 our understanding of the potential effectiveness of this treatment and its potential side effects when compared with a more commonly used treatment (Botulinum Toxin).
Who can participate?
Adults aged 18 or older who have a central nervous system condition such as brain injury (from stroke, trauma, or bleeding), multiple sclerosis, or spinal cord injury can take part. They need to have spasticity-related pain that is suitable for treatment with Botulinum Toxin and cryoneurolysis, and they should have shown a clear benefit from a diagnostic nerve block. They must have at least one rehabilitation goal focused on reducing pain caused by spasticity.
What does the study involve?
Participants will be randomly allocated to receive usual care with Botulinum Toxin (control group) or usual care with Cryoneurolysis (intervention group). We 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.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
Oxford University Hospitals NHS Trust (UK)
When is the study starting and how long is it expected to run for?
May 2025 to November 2027
Who is funding the study?
Pacira BioSciences (USA)
Who is the main contact?
Dr Anton Pick, Anton.Pick@ouh.nhs.uk
Contact information
Scientific, Principal investigator, Public
Oxford Centre for Enablement, Windmill Road
Oxford
OX3 7HE
United Kingdom
| Phone | +44 (0)1865 737306 |
|---|---|
| anton.pick@ouh.nhs.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomized controlled open-label parallel-group crossover study |
| Secondary study design | Randomised controlled trial |
| Scientific title | Individualised Cryoneurolysis to treat pain in the context of spasticity in the upper and lower Extremities: a pilot randomised controlled trial |
| Study acronym | ICE Trial |
| Study objectives | Within the context of treating spasticity arising from central neurological conditions, this study's primary objective it to ascertain variability in goal attainment following cryoneurolysis (in addition to usual care) compared to Botulinum Toxin (in addition to usual care). Secondary objectives: - To assess pain and potential side effects following cryoneurolysis compared to Botulinum Toxin - To test for maintenance of effects of cryoneurolysis compared to Botulinum Toxin (between group comparison) - To test the effects of cryoneurolysis on measures of spasticity, quality and life, and function compared to Botulinum Toxin Exploratory objectives: - To explore patient satisfaction, experience, and anticipated barriers/facilitators to clinical implementation - To explore the potential maintenance of effect of cryoneurolysis (within group comparison) -To explore the effects of cryoneurolysis compared to Botulinum Toxin (within group comparison) |
| Ethics approval(s) |
Approved 02/12/2025, Wales REC 1 (Health and Care Research Wales, Floor 4, Crown Building, Cardiff, CF10 3NQ, United Kingdom; -; Wales.REC1@wales.nhs.uk), ref: 25/WA/0286 |
| Health condition(s) or problem(s) studied | Medical condition: Central neurological condition, including acquired brain injury (e.g. from ischaemic stroke, trauma, or haemorrhage), multiple sclerosis, and spinal cord injury. Medical condition in lay language: Condition affecting the brain or spinal cord Therapeutic areas: Diseases [C] - Nervous System Diseases [C10] |
| Intervention | Randomisation (to cryoneurolysis or control, in 1:1 ratio) will be undertaken by the trial team (Trial coordinator or CI) following baseline, using freely available online randomisation software (rando.la). Randomisation includes minimisation between: diagnosis, sex, time since injury/diagnosis, predominant passive or active goals, and requiring treatment of upper/lower limb/both. Cryoneurolysis: 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. Botulinum 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. |
| Intervention type | Drug |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | botulinum toxin [Botulinum toxin type A] |
| Primary outcome measure(s) |
Variability in goal attainment assessed using the Goal Attainment Scale at 6-weeks post-treatment |
| Key secondary outcome measure(s) |
1. Pain using a numerical rating scale (1–10), DN4, NPSI, and pressure pain thresholds (PPT) — all standard measures, carried out at 6, 12, 18, and 24 weeks. |
| Completion date | 01/11/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 99 Years |
| Sex | All |
| Target sample size at registration | 50 |
| Key inclusion criteria | 1. 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. 2. Male or Female, aged 18 years or above. 3. Diagnosed with a central neurological condition, including acquired brain injury (e.g. from ischaemic stroke, trauma, or haemorrhage), multiple sclerosis, and spinal cord injury. 4. 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. 5. At least one rehabilitation goal related to the management of pain resulting from spasticity. |
| Key exclusion criteria | 1. Participant has received Botulinum toxin or cryoneurolysis within the last 90 days 2. Raynaud’s syndrome 3. Cryoglobulinaemia 4. Cold urticaria 5. Bleeding disorders 6. Prescribed, or taking antibiotics from the aminoglycoside family 7. Localised infection at the intended treatment site 8. Planned oral antispasmodic medication dose changes 9. Pregnancy, breastfeeding, or planning pregnancy in the trial period 10. Scheduled elective surgery or other procedures requiring general anaesthesia during the trial. 11. 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. 12. 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. |
| Date of first enrolment | 01/03/2026 |
| Date of final enrolment | 01/09/2027 |
Locations
Countries of recruitment
- United Kingdom
Study participating centre
Windmill Road
Headington
Oxford
OX3 7HE
England
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Anton Pick, anton.pick@ouh.nhs.uk, and with a data sharing agreement. Only fully anonymised data will be provided and only upon a reasonable request made by email. |
Editorial Notes
03/12/2025: ISRCTN received notification of combined HRA/MHRA approval for this trial on 03/12/2025.
09/09/2025: Study's existence confirmed by Health Research Authority (HRA) (UK).
