Upper Limb Nerve Cryoneurolysis is Non Inferior to the Usual Care and Has Therapeutic Add Value in Dealing With Shoulder Pain and Functional Problems Caused by Spasticity and Motor Impairment

NCT06782464 | Recruiting

• 1 other identifier: spastiCRYO-UL
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is part of the spastiCRYO clinical research project. The primary objective of this clinical trial is to test the hypothesis: "Upper limb nerve cryoneurolysis is non inferior to the usual care and has therapeutic add value in dealing with shoulder pain and functional problems caused by spasticity and motor impairment". It is a non-inferiority study on the referred topic, comparing the therapeutic effect (improvement in function and pain) of cryoneurolysis of selected nerves (lateral pectoral nerve and thoracodorsal nerve) with the usual care: intramuscular botulinum neurotoxin type A (BoNT-A) injection of pectoralis major, teres major and subscapularis muscles. The hypothesis is that cryoneurolysis is not inferior to the usual care in terms of magnitude of the therapeutic effect and might have a therapeutic add-value in terms of duration of that effect. Two secondary hypotheses are firstly, that cryoneurolysis is a safe procedure that can be deployed in a rehabilitation hospital setting with minimum requirements to perform mini-invasive procedures and secondly that selecting patients who might benefit from this treatment is straightforward. To test these hypotheses, the research team will gather, analyse and compare outcome measures data from the endpoints which are the changes along the trial duration in shoulder pain, upper limb function, involved muscles spasticity, shoulder range of motion (abduction and external rotation) level of impairment, and follow-up of potential adverse effects in two independent and equivalent groups of participants who have shoulder pain and functional limitations caused by spasticity and are in a stable phase of their condition. Participants in one group (cryoneurolysis arm) have one session of selected nerves ultrasound and neurostimulation guided cryoneurolysis and participants in the other group (BoNT-A arm) have one session of ultrasound and neurostimulation guided injection of BoNT-A in the pectoralis major, teres major and subscapularis. The participants of the two groups follow an upper limb analogous rehabilitation program for 24 weeks after each intervention. Longitudinal follow-up in the trial will take 24 weeks. In a real-world scenario, within 24 weeks the effect of Bont-A intramuscular injection has already waned, and the procedure should be repeated. Secondary objectives are to compare changes in upper limb sensory function and electroneuromyographic parameters with the intention to understand the cryoneurolysis mechanism of action and the reversibility of this mini-invasive intervention. Changes in quality-of-life dimension of participants is a secondary endpoint as well.

Conditions

Hemiplegia; Spasticity; Shoulder Spasticity; Shoulder Stiffness; Stroke; Multiple Sclerosis; Traumatic Brain Injury; Spinal Cord Injury

Keywords

cryoneurolysis; spasticity; pain; stroke; traumatic brain injury; spinal cord injury

Outcome Measures

Primary Outcomes (2)

• Change in active Range of motion shoulder

  Active Range of Motion (AROM) measure in angles (Deg) at the shoulder assesses joint mobility through voluntary movement by the patient. The healthcare professional instructs the patient to perform the following motions: Flexion: Arm moves forward and upward. Extension: Arm moves backward. Abduction: Arm lifts outward to the side. Adduction: Arm moves across the body. Internal Rotation: Arm rotates inward (e.g., hand behind back). External Rotation: Arm rotates outward (e.g., hand behind head). The clinician observes for range, quality, symmetry, and compensatory movements. A goniometer measures the motion in degrees, compared to normative or baseline values. AROM helps identify muscle strength, joint limitations, and functional deficits, providing a reliable outcome measure in rehabilitation.

  baseline, week 1, 4, 12 and 24

• Change in passive range of motion of shoulder

  Passive Range of Motion (PROM), measured in angles (Deg) performed by a healthcare professional, assesses joint mobility in the shoulder. The clinician gently moves the shoulder through its full range while the patient remains relaxed, measuring: Flexion (forward arm movement) Extension (backward arm movement) Abduction (arm movement away from the body) Adduction (arm movement toward the body) Internal rotation (arm rotates inward) External rotation (arm rotates outward). A goniometer records the motion in degrees, compared to normative values or baseline measurements. PROM is essential for identifying joint stiffness, contractures, or spasticity and tracking mobility changes over time, making it a reliable outcome measure in rehabilitation.

  baseline, week 1,4,12,24

Secondary Outcomes (7)

• Change in muscle tone muscles controlling the shoulder

  Baseline, week 1, 4, 12, 24

• Change in nociceptive pain: Visual analogue scale

  Baseline, week 1,4,12,24

• Upper limb fonction - Fugl-Meyer Assessment (FMA)

  Baseline, Week 24

• change in Quality of Life

  Baseline, Week 24

• Tardieu Modified scale

  baseline, week 1, 4, 12 and 24

Study Arms (2)

Intramuscular injection of onabotulinumtoxinA

ACTIVE COMPARATOR

Participants allocated to this group have intramuscular injections, guided by ultrasound and electrical neurostimulation, of BoNT-A (ona botulinum toxin A) to the pectoralis major (75 UI), subscapularis (75 UI) and teres major (50 UI), dilution 100UI/ml. These muscles selection and doses are chosen according to a literature review incriminating these 3 muscles as the responsible for a common spastic pattern of shoulder adduction and internal rotation and contributing to the shoulder pain.

Procedure: Treatment

Ultrasound-guided Cryoneurolysis with Metrum Cryo-painless S device

EXPERIMENTAL

The cryoneurolysis intervention is performed by a trained and experienced physician. Ultrasound guided cryoneurolysis to the lateral pectoral nerve and to the thoracodorsal nerve is the intervention in this group. The 3 parts of the pectoral major muscle (clavicular, sternal and costal) innervated by different branches of the lateral pectoral nerve might be targeted as needed80. The cryoneurolysis device being used is the "Cryo-S Painless" produced by Metrum, a manufacturer based in Poland. The cryoprobes have a caliber of 1.3 mm. These devices hold medical certification (Conformité Européenne CE) for cryoanalgesia within the European Union. Technical and certification files are provided to the Regulatory agencies in Luxembourg. (https://www.metrum.com.pl/produkty/cryo-s-painless-2/?lang=en ). Several precautions steps are taken to prevent the incidence of adverse effects.

Procedure: Treatment

Interventions

Treatment PROCEDURE

Treatment

Intramuscular injection of onabotulinumtoxinA; Ultrasound-guided Cryoneurolysis with Metrum Cryo-painless S device

Eligibility Criteria

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

You may qualify if:

• Be over 18 years old.
• Have a clinically and functionally stable condition.
• Present spastic hemiplegia of the upper limb caused by a stroke, traumatic, or hypoxic brain event occurring more than 6 months before the study.
• The paretic upper limb must present significant spastic plegia at the shoulder adductors and/or shoulder internal rotators (≥ 1+ on the Modified Ashworth Scale).
• Have a Visual Analogue Scale (VAS) pain score \> 40/100 mm.
• Have spasticity causing limitations in providing care.
• Have the cognitive capacity to make informed decisions. A comprehensive explanation of the study will be provided orally and in writing to participants and a trusted relative of their choosing.
• Maintain any medications on a stable schedule.
• Accept and have access to an interdisciplinary rehabilitation program and standardized evaluation sessions throughout the study.

You may not qualify if:

• In the investigator's opinion, the subject will be exposed to unacceptable risk by participation.
• Previous intervention or condition that altered the target neural anatomy of the upper limb.
• Any injection (neurolytic, sclerosing, anesthesia, etc.) to the upper limb within the last 4 months.
• Spasticity invasive treatment such as intrathecal baclofen during the trial.
• Current enrollment in an investigational drug or device study targeting spasticity management.
• Pregnancy or lactation.
• Allergy or intolerance to local anesthesia/BoNT-A.
• Contraindications to BoNT-A administration, such as:
• Myasthenia Gravis
• Eaton-Lambert syndrome
• Possible drug interactions (e.g., aminoglycosides and BoNT-A)
• Any local skin condition at the treatment site that may adversely affect treatment or outcomes.
• Chronic medication use (prescription or over-the-counter) that, in the investigator's opinion, would affect study participation or subject safety.
• Contraindications to cryoneurolysis, including:
• Diagnosis of cryoglobulinemia

Sponsors & Collaborators

• Centre National de Rééducation Fonctionnelle et de Réadaptation: lead

Study Sites (1)

Rehazenter, Centre National de Rééducation fonctionnelle et de Réadaptation

Luxembourg, 2674, Luxembourg

RECRUITING

Related Publications (1)

• Verduzco-Gutierrez M, Raghavan P, Pruente J, Moon D, List CM, Hornyak JE, Gul F, Deshpande S, Biffl S, Al Lawati Z, Alfaro A. AAPM&R consensus guidance on spasticity assessment and management. PM R. 2024 Aug;16(8):864-887. doi: 10.1002/pmrj.13211. Epub 2024 May 21.

  PMID: 38770827 RESULT

MeSH Terms

Conditions

Hemiplegia; Muscle Spasticity; Stroke; Multiple Sclerosis; Brain Injuries, Traumatic; Spinal Cord Injuries; Pain

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

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

Central Study Contacts

José A Carvalho Pereira, M.D.

CONTACT

+35226984010; jose.pereira@rehazenter.lu

Frederic Dierick, PhD

CONTACT

352269894310

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The upper limb clinical trial of the spastiCRYO research project is a multinational interventional randomized controlled trial. As stated previously, it compares the clinical effectiveness of an interventional session consisting in ultrasound guided peripheral pectoral lateral and thoracodorsal nerves cryoneurolysis plus an upper limb rehabilitation programme with the standard care, which is an interventional session consisting in BoNT-A intramuscular injection in pectoralis major, subscapularis and teres major muscles, plus an upper limb rehabilitation program, for the treatment of shoulder pain and functional problems caused by spasticity of the upper limb. Setting The trial is conducted in two Rehabilitation Hospitals in different countries (multicentric): In Portugal and Luxembourg

Study Record Dates

• First Submitted: December 13, 2024
• First Posted: January 17, 2025
• Study Start: December 12, 2024
• Primary Completion (Estimated): December 12, 2028
• Study Completion (Estimated): December 12, 2028
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Shared after post-hoc analysis data

Locations

LU (1)