Crioneurosis individualizada para tratar el dolor en el contexto de la espasticidad en las extremidades superiores e inferiores (ICE)
Crioneurolisis Individualizada para Tratar el Dolor en el Contexto de la Espasticidad en las Extremidades Superiores e Inferiores (ICE): un Ensayo Piloto Controlado Aleatorizado
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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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).
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 4
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Anton Pick, MBChB
- Número de teléfono: (+44) 01865 737306
- Correo electrónico: anton.pick@ouh.nhs.uk
Copia de seguridad de contactos de estudio
- Nombre: Barbara Robinson, MSc
- Correo electrónico: barbara.robinson@ndcn.ox.ac.uk
Ubicaciones de estudio
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Oxford, Reino Unido, OX3 7HE
- Reclutamiento
- Oxford Centre for Enablement (OUH NHS-FT)
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Contacto:
- Anton Pick, MBChB
- Número de teléfono: +44 01865 737 306
- Correo electrónico: anton.pick@ouh.nhs.uk
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Investigador principal:
- Anton Pick, MBChB
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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 de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación cruzada
- Enmascaramiento: Único
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Crioneurólisis (+ cuidado habitual)
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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.
Otros nombres:
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Comparador activo: Toxina Botulínica (+ cuidado habitual)
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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.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Goal Attainment Scale
Periodo de tiempo: 6-weeks post-treatment
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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
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Self-reported Pain
Periodo de tiempo: 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
|
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Douleur Neuropathique en 4 (DN4)
Periodo de tiempo: 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
|
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Neuropathic Pain Symptom Inventory (NPSI)
Periodo de tiempo: 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
|
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Side Effects
Periodo de tiempo: 6, 12, 18, and 24 weeks post-treatment
|
As measured by self-report side effects questionnaire |
6, 12, 18, and 24 weeks post-treatment
|
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Goal Attainment Scale
Periodo de tiempo: 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
|
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Modified Ashworth Scale
Periodo de tiempo: 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
|
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Modified Tardieu Scale
Periodo de tiempo: 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
|
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Spasticity
Periodo de tiempo: 6- and 12-weeks post treatment
|
Directly assessed by measuring the muscle activity to a passive stretch |
6- and 12-weeks post treatment
|
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Range of Motion
Periodo de tiempo: 6- and 12-weeks post treatment
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Assessed using a goniometer |
6- and 12-weeks post treatment
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Patient Reported Impact of Spasticity Measure (PRISM)
Periodo de tiempo: 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
|
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EQ5D
Periodo de tiempo: 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
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Spasticity Related Quality of Life instrument (SQoL-6D)
Periodo de tiempo: 6- and 12-weeks post treatment
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Questionnaire assessing spasticity related quality of life (range 0 - 24, higher score indicating worse condition) |
6- and 12-weeks post treatment
|
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Barthel Index
Periodo de tiempo: 6- and 12-weeks post treatment
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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
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Gait assessment - Walking Speed
Periodo de tiempo: 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
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Gait assessment - Gait profile score
Periodo de tiempo: 6- and 12-weeks post treatment
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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
|
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Leg Activity Measure (LEG-A)
Periodo de tiempo: 6- and 12-weeks post treatment
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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
|
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Shriners Hospital Upper Extremity Evaluation (SHUEE)
Periodo de tiempo: 6- and 12-weeks post treatment
|
Kinematic assessment of upper extremity function using motion capture cameras. |
6- and 12-weeks post treatment
|
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Arm Activity Measure (ARM-A)
Periodo de tiempo: 6- and 12-weeks post treatment
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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
|
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Functional Assessment Test for Upper Limb (FAST-UL)
Periodo de tiempo: 6- and 12-weeks post treatment
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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
|
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Pressure Pain Thresholds (PPT)
Periodo de tiempo: 6, 12, 18, and 24 weeks post-treatment
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Sensory testing using a manual algometer to assess pain thresholds. |
6, 12, 18, and 24 weeks post-treatment
|
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Feedback Questionnaire/Interview
Periodo de tiempo: 24 weeks post treatment
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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
|
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Sleep Condition Indicator
Periodo de tiempo: 6, 12, 18, and 24 weeks post-treatment
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Questionnaire assessing self-reported insomnia symptoms (range 0-32, higher numbers indicate less symptoms of insomnia) |
6, 12, 18, and 24 weeks post-treatment
|
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Goal Attainment Scale
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 18- and 24-weeks post-treatment
|
Assessed using a goniometer |
18- and 24-weeks post-treatment
|
|
Patient Reported Impact of Spasticity Measure (PRISM)
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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
|
Colaboradores e Investigadores
Patrocinador
Publicaciones y enlaces útiles
Publicaciones Generales
- 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.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Manifestaciones neurológicas
- Enfermedades musculoesqueléticas
- Trastornos cerebrovasculares
- Enfermedades Cerebrales
- Enfermedades del Sistema Nervioso Central
- Enfermedades del Sistema Nervioso
- Enfermedades Vasculares
- Enfermedades cardiovasculares
- Enfermedades Musculares
- Hipertonía muscular
- Manifestaciones Neuromusculares
- Heridas y Lesiones
- Enfermedades autoinmunes
- Enfermedades del sistema inmunológico
- Enfermedades Autoinmunes Desmielinizantes, SNC
- Enfermedades Autoinmunes del Sistema Nervioso
- Enfermedades desmielinizantes
- Trauma craneoencefálico
- Trauma, Sistema Nervioso
- Enfermedades de la médula espinal
- Condiciones Patológicas, Signos y Síntomas
- Signos y síntomas
- Dolor
- Espasticidad muscular
- Carrera
- Esclerosis múltiple
- Lesiones Cerebrales
- Lesiones de la médula espinal
- Aminoácidos, péptidos y proteínas
- Proteínas
- Procedimientos quirúrgicos, operativo
- Factores biológicos
- Hidrolasas
- Enzimas
- Enzimas y coenzimas
- Anestesia y analgesia
- Procedimientos neurociruúrgicos
- Metaloendopeptidasas
- Endopeptidasas
- Hidrolasas peptídicas
- Metaloproteasas
- Proteínas bacterianas
- Toxinas bacterianas
- Toxinas, biológicas
- Anestesia, conducción
- Anestesia
- Denervación
- Toxinas botulínicas tipo A
- Toxinas botulínicas
- incobotulinumtoxinaA
- Bloqueo nervioso
Otros números de identificación del estudio
- PID 18403
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
De-identified data are available upon reasonable request.
Marco de tiempo para compartir IPD
Following publication of results
Criterios de acceso compartido de IPD
Available upon reasonable request
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
Información sobre medicamentos y dispositivos, documentos del estudio
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Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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