痙縮の文脈における上肢および下肢の疼痛を治療するための個別化低温神経溶解術 (ICE)
痙縮を伴う上下肢の疼痛に対する個別化クリオ神経溶解療法（ICE）：パイロット無作為化比較試験
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.
調査の概要
詳細な説明
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).
研究の種類
入学 (推定)
段階
- フェーズ 4
連絡先と場所
研究連絡先
- 名前：Anton Pick, MBChB
- 電話番号：(+44) 01865 737306
- メール：anton.pick@ouh.nhs.uk
研究連絡先のバックアップ
- 名前：Barbara Robinson, MSc
- メール：barbara.robinson@ndcn.ox.ac.uk
研究場所
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Oxford、イギリス、OX3 7HE
- 募集
- Oxford Centre for Enablement (OUH NHS-FT)
-
コンタクト：
- Anton Pick, MBChB
- 電話番号：+44 01865 737 306
- メール：anton.pick@ouh.nhs.uk
-
主任研究者：
- Anton Pick, MBChB
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：クロスオーバー割り当て
- マスキング：独身
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：クリオ神経溶解（＋通常ケア）
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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.
他の名前：
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アクティブコンパレータ：ボツリヌス毒素（+通常のケア）
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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.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Goal Attainment Scale
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Self-reported Pain
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：6- and 12-weeks post treatment
|
Assessed using a goniometer |
6- and 12-weeks post treatment
|
|
Patient Reported Impact of Spasticity Measure (PRISM)
時間枠：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
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Feedback Questionnaire/Interview
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：18- and 24-weeks post-treatment
|
Assessed using a goniometer |
18- and 24-weeks post-treatment
|
|
Patient Reported Impact of Spasticity Measure (PRISM)
時間枠：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
時間枠：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)
時間枠：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
時間枠：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)
時間枠：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)
時間枠：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
|
協力者と研究者
出版物と役立つリンク
一般刊行物
- 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.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
- 神経症状
- 筋骨格疾患
- 脳血管障害
- 脳疾患
- 中枢神経系疾患
- 神経系疾患
- 血管疾患
- 心血管疾患
- 筋肉の病気
- 筋緊張亢進
- 神経筋症状
- 傷やけが
- 自己免疫疾患
- 免疫系疾患
- 脱髄性自己免疫疾患、CNS
- 神経系の自己免疫疾患
- 脱髄疾患
- 頭蓋脳外傷
- 外傷、神経系
- 脊髄疾患
- 病理学的状態、徴候および症状
- 徴候と症状
- 痛み
- 筋肉の痙性
- 脳卒中
- 多発性硬化症
- 脳損傷
- 脊髄損傷
- アミノ酸、ペプチド、およびタンパク質
- タンパク質
- 外科的処置、手術
- 生物学的要因
- ヒドロラーゼ
- 酵素
- 酵素と補酵素
- 麻酔と鎮痛
- 脳神経外科手術
- メタロエンドペプチダーゼ
- エンドペプチダーゼ
- ペプチドヒドロラーゼ
- メタロプロテアーゼ
- 細菌タンパク質
- 細菌毒素
- 毒素、生物学的
- 麻酔、伝導
- 麻酔
- 除神経
- ボツリヌス毒素、A 型
- ボツリヌス毒素
- インコボツリヌス毒素A
- 神経ブロック
その他の研究ID番号
- PID 18403
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
De-identified data are available upon reasonable request.
IPD 共有時間枠
Following publication of results
IPD 共有アクセス基準
Available upon reasonable request
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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