Individualised Cryoneurolysis to Treat Pain in the Context of Spasticity in the Upper and Lower Extremities

NCT07303582 | Recruiting Phase 4

• 1 other identifier: PID 18403
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Centreal Neurological Condition; Acquired Brain Injury (Including Stroke); Multiple Sclerosis; Spinal Cord Injury

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

Outcome Measures

Primary Outcomes (1)

• Goal Attainment Scale

  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).

  6-weeks post-treatment

Secondary Outcomes (20)

• Self-reported Pain

  6, 12, 18, and 24 weeks post-treatment

• Douleur Neuropathique en 4 (DN4)

  6, 12, 18, and 24 weeks post-treatment

• Neuropathic Pain Symptom Inventory (NPSI)

  6, 12, 18, and 24 weeks post-treatment

• Side Effects

  6, 12, 18, and 24 weeks post-treatment

• Goal Attainment Scale

  12-weeks post treatment

Other Outcomes (13)

• Feedback Questionnaire/Interview

  24 weeks post treatment

• Sleep Condition Indicator

  6, 12, 18, and 24 weeks post-treatment

• Goal Attainment Scale

  18- and 24-weeks post-treatment

Study Arms (2)

Cryoneurolysis (+ usual care)

EXPERIMENTAL

Procedure: Cryoneurolysis

Botulinum Toxin (+ usual care)

ACTIVE COMPARATOR

Interventions

Botulinum toxin PROCEDURE

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.

Also known as: Botox, Xeomin, Chemodenervation, BoNT-A

Cryoneurolysis PROCEDURE

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.

Also known as: Iovera, Cryoneurotomy, Cryoneurectomy, Cryoanalgesia

Cryoneurolysis (+ usual care)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Oxford University Hospitals NHS Trust: lead
• University of Oxford: collaborator
• Bournemouth University: collaborator

Study Sites (1)

Oxford Centre for Enablement (OUH NHS-FT)

Oxford, OX3 7HE, United Kingdom

RECRUITING

Related Publications (9)

• Wissel J, Manack A, Brainin M. Toward an epidemiology of poststroke spasticity. Neurology. 2013 Jan 15;80(3 Suppl 2):S13-9. doi: 10.1212/WNL.0b013e3182762448.

  PMID: 23319481 BACKGROUND

• Winston P, Mills PB, Reebye R, Vincent D. Cryoneurotomy as a Percutaneous Mini-invasive Therapy for the Treatment of the Spastic Limb: Case Presentation, Review of the Literature, and Proposed Approach for Use. Arch Rehabil Res Clin Transl. 2019 Oct 17;1(3-4):100030. doi: 10.1016/j.arrct.2019.100030. eCollection 2019 Dec.

  PMID: 33543059 BACKGROUND

• Whitehead AL, Julious SA, Cooper CL, Campbell MJ. Estimating the sample size for a pilot randomised trial to minimise the overall trial sample size for the external pilot and main trial for a continuous outcome variable. Stat Methods Med Res. 2016 Jun;25(3):1057-73. doi: 10.1177/0962280215588241. Epub 2015 Jun 19.

  PMID: 26092476 BACKGROUND

• Turner-Stokes L, Jacinto J, Fheodoroff K, Brashear A, Maisonobe P, Lysandropoulos A, Ashford S; Upper Limb International Spasticity (ULIS-III) study group. Longitudinal goal attainment with integrated upper limb spasticity management including repeat injections of botulinum toxin A: Findings from the prospective, observational Upper Limb International Spasticity (ULIS-III) cohort study. J Rehabil Med. 2021 Feb 24;53(2):jrm00157. doi: 10.2340/16501977-2801.

  PMID: 33616192 BACKGROUND

• Skoog B, Jakobsson KE. Prevalence of Spasticity and Below-Level Neuropathic Pain Related to Spinal Cord Injury Level and Damage to the Lower Spinal Segments. J Rehabil Med Clin Commun. 2020 Mar 8;3:1000039. doi: 10.2340/20030711-1000039. eCollection 2020.

  PMID: 33884141 BACKGROUND

• Rizzo MA, Hadjimichael OC, Preiningerova J, Vollmer TL. Prevalence and treatment of spasticity reported by multiple sclerosis patients. Mult Scler. 2004 Oct;10(5):589-95. doi: 10.1191/1352458504ms1085oa.

  PMID: 15471378 BACKGROUND

• Kim PS, Ferrante FM. Cryoanalgesia: a novel treatment for hip adductor spasticity and obturator neuralgia. Anesthesiology. 1998 Aug;89(2):534-6. doi: 10.1097/00000542-199808000-00036. No abstract available.

  PMID: 9710418 BACKGROUND

• Biel E, Aroke EN, Maye J, Zhang SJ. The applications of cryoneurolysis for acute and chronic pain management. Pain Pract. 2023 Feb;23(2):204-215. doi: 10.1111/papr.13182. Epub 2022 Dec 4.

  PMID: 36370129 BACKGROUND

• Bhimani R, Anderson L. Clinical understanding of spasticity: implications for practice. Rehabil Res Pract. 2014;2014:279175. doi: 10.1155/2014/279175. Epub 2014 Sep 4.

  PMID: 25276432 BACKGROUND

MeSH Terms

Conditions

Brain Injuries; Multiple Sclerosis; Spinal Cord Injuries; Muscle Spasticity; Pain; Stroke

Interventions

Botulinum Toxins; Botulinum Toxins, Type A; incobotulinumtoxinA; Nerve Block

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Spinal Cord Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Anesthesia, Conduction; Anesthesia; Anesthesia and Analgesia; Denervation; Neurosurgical Procedures; Surgical Procedures, Operative

Central Study Contacts

Anton Pick, MBChB

CONTACT

(+44) 01865 737306; anton.pick@ouh.nhs.uk

Barbara Robinson, MSc

CONTACT

barbara.robinson@ndcn.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Primary Investigator

Model Details: 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.

Study Record Dates

• First Submitted: September 10, 2025
• First Posted: December 26, 2025
• Study Start: December 2, 2025
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: December 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Following publication of results
• Access Criteria: Available upon reasonable request

Locations

GB (1)