Cryoneurolyse individualisée pour traiter la douleur dans le contexte de la spasticité des membres supérieurs et inférieurs (ICE)
Cryoneurolyse individualisée pour traiter la douleur dans le contexte de la spasticité des membres supérieurs et inférieurs (ICE) : un essai contrôlé randomisé pilote
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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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).
Type d'étude
Inscription (Estimé)
Phase
- Phase 4
Contacts et emplacements
Coordonnées de l'étude
- Nom: Anton Pick, MBChB
- Numéro de téléphone: (+44) 01865 737306
- E-mail: anton.pick@ouh.nhs.uk
Sauvegarde des contacts de l'étude
- Nom: Barbara Robinson, MSc
- E-mail: barbara.robinson@ndcn.ox.ac.uk
Lieux d'étude
-
-
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Oxford, Royaume-Uni, OX3 7HE
- Recrutement
- Oxford Centre for Enablement (OUH NHS-FT)
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Contact:
- Anton Pick, MBChB
- Numéro de téléphone: +44 01865 737 306
- E-mail: anton.pick@ouh.nhs.uk
-
Chercheur principal:
- Anton Pick, MBChB
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation croisée
- Masquage: Seul
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: Cryoneurolyse (+ soins habituels)
|
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.
Autres noms:
|
|
Comparateur actif: Toxine botulique (+ soins habituels)
|
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.
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Goal Attainment Scale
Délai: 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). |
6-weeks post-treatment
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Self-reported Pain
Délai: 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). |
6, 12, 18, and 24 weeks post-treatment
|
|
Douleur Neuropathique en 4 (DN4)
Délai: 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). |
6, 12, 18, and 24 weeks post-treatment
|
|
Neuropathic Pain Symptom Inventory (NPSI)
Délai: 6, 12, 18, and 24 weeks post-treatment
|
Questionnaire used to quantify neuropathic pain (range 0 - 100, higher scores reflect worse neuropathic pain). |
6, 12, 18, and 24 weeks post-treatment
|
|
Side Effects
Délai: 6, 12, 18, and 24 weeks post-treatment
|
As measured by self-report side effects questionnaire |
6, 12, 18, and 24 weeks post-treatment
|
|
Goal Attainment Scale
Délai: 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). |
12-weeks post treatment
|
|
Modified Ashworth Scale
Délai: 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). |
6- and 12-weeks post treatment
|
|
Modified Tardieu Scale
Délai: 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). |
6- and 12-weeks post treatment
|
|
Spasticity
Délai: 6- and 12-weeks post treatment
|
Directly assessed by measuring the muscle activity to a passive stretch |
6- and 12-weeks post treatment
|
|
Range of Motion
Délai: 6- and 12-weeks post treatment
|
Assessed using a goniometer |
6- and 12-weeks post treatment
|
|
Patient Reported Impact of Spasticity Measure (PRISM)
Délai: 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"). |
6- and 12-weeks post treatment
|
|
EQ5D
Délai: 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. |
6- and 12-weeks post treatment
|
|
Spasticity Related Quality of Life instrument (SQoL-6D)
Délai: 6- and 12-weeks post treatment
|
Questionnaire assessing spasticity related quality of life (range 0 - 24, higher score indicating worse condition) |
6- and 12-weeks post treatment
|
|
Barthel Index
Délai: 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) |
6- and 12-weeks post treatment
|
|
Gait assessment - Walking Speed
Délai: 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. |
6- and 12-weeks post treatment
|
|
Gait assessment - Gait profile score
Délai: 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. |
6- and 12-weeks post treatment
|
|
Leg Activity Measure (LEG-A)
Délai: 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.) |
6- and 12-weeks post treatment
|
|
Shriners Hospital Upper Extremity Evaluation (SHUEE)
Délai: 6- and 12-weeks post treatment
|
Kinematic assessment of upper extremity function using motion capture cameras. |
6- and 12-weeks post treatment
|
|
Arm Activity Measure (ARM-A)
Délai: 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.) |
6- and 12-weeks post treatment
|
|
Functional Assessment Test for Upper Limb (FAST-UL)
Délai: 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). |
6- and 12-weeks post treatment
|
|
Pressure Pain Thresholds (PPT)
Délai: 6, 12, 18, and 24 weeks post-treatment
|
Sensory testing using a manual algometer to assess pain thresholds. |
6, 12, 18, and 24 weeks post-treatment
|
Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Feedback Questionnaire/Interview
Délai: 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. |
24 weeks post treatment
|
|
Sleep Condition Indicator
Délai: 6, 12, 18, and 24 weeks post-treatment
|
Questionnaire assessing self-reported insomnia symptoms (range 0-32, higher numbers indicate less symptoms of insomnia) |
6, 12, 18, and 24 weeks post-treatment
|
|
Goal Attainment Scale
Délai: 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). |
18- and 24-weeks post-treatment
|
|
Modified Ashworth Scale
Délai: 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). |
18- and 24-weeks post-treatment
|
|
Modified Tardieu Scale
Délai: 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). |
18- and 24-weeks post-treatment
|
|
Spasticity
Délai: 18- and 24-weeks post-treatment
|
Directly assessed by measuring the muscle activity to a passive stretch |
18- and 24-weeks post-treatment
|
|
Range of motion
Délai: 18- and 24-weeks post-treatment
|
Assessed using a goniometer |
18- and 24-weeks post-treatment
|
|
Patient Reported Impact of Spasticity Measure (PRISM)
Délai: 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") |
18- and 24-weeks post-treatment
|
|
EQ5D
Délai: 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. |
18- and 24-weeks post-treatment
|
|
Spasticity Related Quality of Life instrument (SQoL-6D)
Délai: 18- and 24-weeks post-treatment
|
Questionnaire assessing spasticity related quality of life (range 0 - 24, higher score indicating worse condition) |
18- and 24-weeks post-treatment
|
|
Barthel Index
Délai: 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) |
18- and 24-weeks post-treatment
|
|
Leg Activity Measure (LEG-A)
Délai: 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.) |
18- and 24-weeks post-treatment
|
|
Arm Activity Measure (ARM-A)
Délai: 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.) |
18- and 24-weeks post-treatment
|
Collaborateurs et enquêteurs
Parrainer
Publications et liens utiles
Publications générales
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Manifestations neurologiques
- Maladies musculo-squelettiques
- Troubles cérébrovasculaires
- Maladies du cerveau
- Maladies du système nerveux central
- Maladies du système nerveux
- Maladies vasculaires
- Maladies cardiovasculaires
- Maladies musculaires
- Hypertonie musculaire
- Manifestations neuromusculaires
- Blessures et Blessures
- Maladies auto-immunes
- Maladies du système immunitaire
- Maladies auto-immunes démyélinisantes, SNC
- Maladies auto-immunes du système nerveux
- Maladies démyélinisantes
- Traumatisme crânio-cérébral
- Traumatisme, système nerveux
- Maladies de la moelle épinière
- Conditions pathologiques, signes et symptômes
- Signes et symptômes
- La douleur
- Spasticité musculaire
- Accident vasculaire cérébral
- Sclérose en plaques
- Lésions cérébrales
- Blessures à la moelle épinière
- Acides aminés, peptides et protéines
- Protéines
- Procédures chirurgicales, opératoires
- Facteurs biologiques
- Hydrolases
- Enzymes
- Enzymes et coenzymes
- Anesthésie et analgésie
- Procédures neurochirurgicales
- Métalloenpeptidases
- Endopeptidases
- Hydrolases peptidiques
- Métalloproteases
- Protéines bactériennes
- Toxines bactériennes
- Toxines, biologiques
- Anesthésie, conduction
- Anesthésie
- Dénervation
- Toxines botuliques, type A
- Toxines botuliques
- incobotulinumtoxinA
- Bloc nerveux
Autres numéros d'identification d'étude
- PID 18403
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime IPD
De-identified data are available upon reasonable request.
Délai de partage IPD
Following publication of results
Critères d'accès au partage IPD
Available upon reasonable request
Type d'informations de prise en charge du partage d'IPD
- PROTOCOLE D'ÉTUDE
Informations sur les médicaments et les dispositifs, documents d'étude
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