Mechanism of Action of Focal Extracorporeal Shock Waves as a Treatment of Upper Limb Stroke Spasticity: a Pilot Study

Stroke Clinical Trial

— SASHA  

Official title:

Mechanism of Action of Focal Extracorporeal Shock Waves as a Treatment of Upper Limb Stroke Spasticity: a Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06311526
• Other study ID #: 24C303
• Status: Recruiting
• Start date: May 30, 2023
• Est. completion date: April 30, 2025

Study information

• Verified date: March 2024
• Source: Istituto Auxologico Italiano
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Spasticity, common after a stroke, aggravates the patient's motor impairment causing pain and limitation in daily activities such as eating, dressing and walking.

There are different spasticity treatments, such as botulinum neurotoxin, in the first place. Among the emerging therapies is focal extracorporeal shock wave therapy, consisting of a sequence of sonic (mechanical) impulses with high peak pressure.

Systematic reviews highlighted that shock waves effectively improve lower and upper limb spasticity. Moreover, the shock waves therapeutic effect can last up to 12 weeks from the last treatment session.

When used to treat stroke spasticity, the shock waves' mechanism of action is poorly detailed.

On the one side, shock waves could change the physical properties of the muscular tissue (e.g. viscosity, rigidity).

On the other, the shock waves produce a robust mechanical stimulation that massively activates muscle and skin mechanoreceptors (e.g. muscle spindles). This activation would modulate, in turn, the spinal (and supra-spinal) circuits involved in spasticity.

To our knowledge, no study investigated the shock waves mechanism of action in stroke upper limb spasticity.

Research question: do shock waves exert their therapeutic effect on spasticity by changing the muscle's physical properties or by indirectly modulating the excitability of spinal circuits?

Specific aims: To investigate the mechanism of action of shock wave therapy as a treatment of upper limb spasticity after a stroke.

Two major hypotheses will be contrasted: shock waves reduce hypertonia 1) by changing the muscle's physical features or 2) by changing the motoneurons excitability and the excitability of the stretch reflex spinal circuits.

Shock wave therapy is expected to improve spasticity, thus improving the following clinical tests: the Modified Ashworth Scale (an ordinal score of spasticity) and the Functional Assessment for Upper Limb (FAST-UL, an ordinal score of upper limb dexterity).

This clinical improvement is expected to be associated with changes in spastic muscle echotexture assessed with ultrasounds, such as an improvement in the Heckmatt scale (an ordinal score of muscle echotexture in spasticity).

Clinical improvement is also expected to be associated with an improvement in the following neurophysiological parameters: a reduction of the H/Mmax ratio (an index of hyperexcitability of the monosynaptic stretch reflex circuit), a decrease in amplitude of the F waves (a neurophysiological signal reflecting the excitability of single/restricted motoneurones) and an increase of the homosynaptic depression (also known as post-activation depression, reflecting the excitability of the transmission between the Ia fibres and motoneurones).

Understanding the shock wave mechanism of action will lead to a better clinical application of this spasticity treatment.

If the shock waves exert their therapeutic effect by changing the muscle's physical properties, they could be more appropriate for patients with muscle fibrosis on ultrasounds.

On the contrary, if the shock waves work on spasticity by indirectly acting on the nervous system's excitability, then a neurophysiology study could be used to preliminary identify the muscle groups with the most significant neurophysiological alterations, which could be the muscles benefitting the most from this treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: April 30, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria

• age > 18 years

• first hemispheric stroke at least six months ago

• spasticity of wrist and elbow flexors muscles with grade 1 to 3 of the Modified Ashworth Scal

• no botulinum toxin injection in the previous six months

• ability to give informed consent

Exclusion criteria

• anticoagulant medicine

• presence of a pacemaker, an implantable cardioverter defibrillator or other medical devices

• active cancer

• skin lesions at the site of shock wave administration

• an major neurological disease in addition to the hemiparesis (e.g. spastic hemiparesis in a patient who had Parkinson's disease before their stroke).

Related Conditions & MeSH terms

• Hemiparesis
• Hemiplegia
• Muscle Spasticity
• Paresis
• Spasticity as Sequela of Stroke
• Stroke
• Upper Limb Hypertonia

Intervention

Other:
• Extracorporeal Shockwave Therapy
Extracorporeal Shockwave Therapy administered to the belly of spastic muscles of the upper limb.

Locations

Country	Name	City	State
Italy	IRCCS Istituto Auxologico Italiano	Milano	MI

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Auxologico Italiano

Country where clinical trial is conducted

Italy, 

References & Publications (7)

Kohn AF, Floeter MK, Hallett M. Presynaptic inhibition compared with homosynaptic depression as an explanation for soleus H-reflex depression in humans. Exp Brain Res. 1997 Sep;116(2):375-80. doi: 10.1007/pl00005765. — View Citation

Lamy JC, Wargon I, Mazevet D, Ghanim Z, Pradat-Diehl P, Katz R. Impaired efficacy of spinal presynaptic mechanisms in spastic stroke patients. Brain. 2009 Mar;132(Pt 3):734-48. doi: 10.1093/brain/awn310. Epub 2008 Nov 26. — View Citation

Lundbye-Jensen J, Nielsen JB. Immobilization induces changes in presynaptic control of group Ia afferents in healthy humans. J Physiol. 2008 Sep 1;586(17):4121-35. doi: 10.1113/jphysiol.2008.156547. Epub 2008 Jul 3. — View Citation

Manganotti P, Amelio E. Long-term effect of shock wave therapy on upper limb hypertonia in patients affected by stroke. Stroke. 2005 Sep;36(9):1967-71. doi: 10.1161/01.STR.0000177880.06663.5c. Epub 2005 Aug 18. — View Citation

Opara J, Taradaj J, Walewicz K, Rosinczuk J, Dymarek R. The Current State of Knowledge on the Clinical and Methodological Aspects of Extracorporeal Shock Waves Therapy in the Management of Post-Stroke Spasticity-Overview of 20 Years of Experiences. J Clin Med. 2021 Jan 12;10(2):261. doi: 10.3390/jcm10020261. — View Citation

Pierrot-Deseilligny, E. & Burke, D. Contribution of Spinal Pathways to the Pathophysiology of Movement Disorders. The Circuitry of the Human Spinal Cord 565-579 (2012) doi:10.1017/CBO9781139026727.015.

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	M wave and H reflex recruitment curve	Recruitment curves of the Flexor Carpi Radialis muscle of both upper limbs	At baseline, after 7, 14 and 21 days of intervention, at 28 and 84 days after the end of the intervention
Primary	H reflex post-activation depression	Post-activation depression of the Flexor Carpi Radialis H reflex of both sides	At baseline, after 7, 14 and 21 days of intervention, at 28 and 84 days after the end of the intervention
Primary	F waves	F waves of the First Dorsal Interosseus muscles of both upper limbs	At baseline, after 7, 14 and 21 days of intervention, at 28 and 84 days after the end of the intervention
Primary	T reflex	T reflex of the Flexor Carpi Radialis of both sides	At baseline, after 7, 14 and 21 days of intervention, at 28 and 84 days after the end of the intervention
Secondary	Upper limb dexterity measures	Functional Assessment Test for Upper Limb	At baseline, after 7, 14 and 21 days of intervention, at 28 and 84 days after the end of the intervention
Secondary	Ultrasound arm and forearm assessment	Echographic assessment of the arm and forearm muscles	At baseline, after 7, 14 and 21 days of intervention, at 28 and 84 days after the end of the intervention