Randomized, sham-controlled trial to investigate extracorporeal shockwave therapy as an adjunctive treatment for spasticity secondary to spinal cord injury - SUMMARY ABSTRACT Spasticity is experienced by approximately two-thirds of the ~308,620 people living with spinal cord injury (SCI) in the United States.13, 24, 25 Spasticity can negatively impact quality of life (QOL), including employment, social interactions, and psychological and physical health and well-being,3-10 and lead to significant secondary health complications like hospitalizations and chronic pain.3-6, 10-17 Mechanistically, spasticity has both neuronal and rheological components (e.g. infiltration of fatty and connective tissues), which can be targeted for intervention to relieve symptoms. Pharmacological agents are the most commonly utilized treatments for post-SCI spasticity, including the injectable botulinum toxin type-A (e.g. Botox [onabotulinumtoxinA]).36 Botox acts by inhibiting the release of acetylcholine at the neuromuscular junction37 and, while effective, it can carry side effects like atrophy of the injected muscles and does not impact rheological effects of spasticity.18, 47 Focused extracorporeal shockwave therapy (f-ESWT) has emerged as a treatment option for spasticity. Several studies have demonstrated its effectiveness and safety profile in people with stroke,61 including as an adjunctive treatment to Botox.62 However, there have been no published studies in individuals with SCI, and clinical trials are needed to establish its effectiveness and safety in this population prior implementation in clinical practice. We recently concluded a pilot, randomized, sham-controlled trial to establish the effectiveness of f-ESWT. Results were promising, yet recruitment issues limited sample size and study power. The proposed trial builds upon our pilot work by seeking to investigate f-ESWT as an adjunctive treatment to Botox using a randomized, controlled design. Thirty subjects will be enrolled and randomized to receive either Botox and f-ESWT (n=15) or Botox and a sham f-ESWT treatment (n=15). All subjects will receive a single Botox injection into three plantar flexor muscles: medial gastrocnemius, lateral gastrocnemius, and soleus. Participants in the active treatment group will receive 3 sessions of f-ESWT (1 per week for 3 consecutive weeks) following an evidence- based protocol.57, 59 The same protocol will be applied to those in the sham control group, only the shockwave probe will not touch the skin to eliminate a therapeutic effect. Clinical and self-report outcomes of spasticity will be collected at all 5 timepoints (3 treatment visits, 4 and 8 weeks post-treatment). Medial gastrocnemius muscle echogenicity and elasticity will be determined via quantitative ultrasound and shear wave elastography, respectively, to investigate effects of the combined treatment on muscle composition and biomechanical properties; these outcomes will be collected at all timepoints. Magnetic resonance imaging of the lower limb will assist the quantification of muscle volumes, collected at baseline and 4 and 8 weeks post-treatment. If hypotheses are proven, these data will be utilized in the formation of a R01 application to conduct a larger- scale clinical trial with longer term endpoints and more sophisticated quantitative imaging methods.
