Clinical trial NCT06311526: Mechanism of Action of Focal Extracorporeal Shock Waves as a Treatment of Upper Limb Stroke Spasticity: a Pilot Study
Official title: Mechanism of Action of Focal Extracorporeal Shock Waves as a Treatment of Upper Limb Stroke Spasticity: a Pilot Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Stroke
Hemiparesis
Hemiplegia
Spasticity as Sequela of Stroke
Upper Limb Hypertonia
Keywords: Spasticity
Stroke
Extracorporeal Shockwave Therapy
Stroke upper limb impairment
Neurophysiology
Musculoskeletal ultrasound
Lead sponsor: Istituto Auxologico Italiano
Sponsor class: OTHER
First posted: 2024-03-15
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Stroke patients with an upper limb spastic paresis.

Brief 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.


Eligibility criteria: 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).

Primary outcomes:
measure: M wave and H reflex recruitment curve
timeFrame: At baseline, after 7, 14 and 21 days of intervention, at 28 and 84 days after the end of the intervention
measure: H reflex post-activation depression
timeFrame: At baseline, after 7, 14 and 21 days of intervention, at 28 and 84 days after the end of the intervention
measure: F waves
timeFrame: At baseline, after 7, 14 and 21 days of intervention, at 28 and 84 days after the end of the intervention
measure: T reflex
timeFrame: At baseline, after 7, 14 and 21 days of intervention, at 28 and 84 days after the end of the intervention
Secondary outcomes:
measure: Upper limb dexterity measures
timeFrame: At baseline, after 7, 14 and 21 days of intervention, at 28 and 84 days after the end of the intervention
measure: Ultrasound arm and forearm assessment
timeFrame: At baseline, after 7, 14 and 21 days of intervention, at 28 and 84 days after the end of the intervention
Other outcomes:
Locations:
city: Milano
country: Italy
facility: IRCCS Istituto Auxologico Italiano
state: MI
Study officials:
References:
citation: 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.
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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.