NEUROwave - Extracorporeal Shock Wave Therapy (ESWT) in Acute Traumatic Complete (AIS A) and Incomplete (AIS B-D) Cross-sectional Lesions on Motor and Sensory Function Within Six Months After Injury

Study Overview
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Brief Summary
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It has been hypothesized that there are two mechanisms of acute traumatic spinal cord injury (SCI): the primary mechanical damage and the secondary injury due to additional pathological processes initiated by the primary injury. Neurological damage due to laceration, contusion, distraction or compression of the spinal cord is called ''primary injury''. This mechanical injury leads to a cascade of biochemical and pathological changes, described as ''secondary injury'', which occurs minutes to weeks after the initial trauma and causes further neurological deterioration. This secondary cascade involves vascular changes, an inflammatory response, neurotoxicity, apoptosis and glial scarring, and further compromises neurological impairment after traumatic spinal cord injury. Edema, ischemia and loss of autoregulation continue to spread bi-directionally from the initial lesion along the spinal cord for up to 72 hours after the trauma. It has been postulated that the damage caused by the primary injury mechanism is irreversible and therapeutic approaches in recent years have focused on modulating the secondary injury cascade. Researchers found significantly greater numbers of myelinated fibers in peripheral nerves after a single ESWT application in an experimental model on rats after a homotopic nerve autograft into the sciatic nerve. In another study a spinal cord ischemia model in mice was performed. ESWT was applied immediately after surgery and the treated animals showed a significantly better motor function and decreased neuronal degeneration compared to the control group within the first 7 days after surgery. Researchers investigated the effect of low-energy ESWT for the duration of three weeks on a thoracic spinal cord contusion injury model in rats. Animals in the ESWT group demonstrated significantly better locomotor improvement and reduced neuronal loss compared to the control animals at 7, 35, and 42 days after contusion. It has been postulated previously, that ESWT improves the metabolic activity of various cell types and induces an improved rate of axonal regeneration. ESWT might be a promising therapeutic strategy in the treatment of traumatic SCI. The underlying study aims to investigate the effect of ESWT after acute traumatic spinal cord injury in humans within 48 hours of trauma in order to intervene in the secondary injury phase with the objective to reduce the extent of neuronal damage.

Official Title
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The Effect of Extracorporeal Shock Wave Therapy (ESWT) in Acute Traumatic Complete (AIS A) and Incomplete (AIS B-D) Cross-sectional Lesions on Motor and Sensory Function Within Six Months After Injury: A Two-arm Three-stage Adaptive, Prospective, Multi-center, Randomized, Double-blind, Placebo-controlled Clinical Trial

Conditions
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Acute Traumatic Spinal Cord Injury

Intervention / Treatment
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* Device: Shock waves
* Device: dummy head


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with acute traumatic spinal injuries who are awake, responsive, and oriented at admission Patients from the age of 18 years Admission to hospital within 24 hours after injury Written consent to participate in the study Participation in the Austrian Spinal Cord Injury Study (ASCIS)-Registry (only for the Austrian hospitals) Exclusion Criteria: Patients who cannot cooperate or are not capable to give consent to participate Serious traumatic brain injuries that prevent accurate participation in study procedures and/or adequacy of informed consent Participation in other interventional clinical trials Serious concomitant injuries that prevent the neurological initial assessment Preexisting neurological conditions that affect the primary endpoint of the study and potentially mask or reduce the therapeutic effect of the ESWT application High dose administration of corticosteroids Complete spinal cord transection Patients with pacemakers or implantable defibrillators Patients who are using devices which are sensitive to electromagnetic radiation (potential) Pregnancy Patients with tumors Patients with severe coagulation disorders

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two-arm three-stage adaptive, prospective, multi-center, randomized, double-blind, placebo-controlled clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ESWT<br>The extracorporeal shockwave therapy is applied once at the level of lesion and 5 segments above and below; or below the occiput (in lesions higher than C6) and above the sacrum (in lesions lower than T12). In addition, the ESWT is applied to the soles of both feet on the medial side of the plantar surface. The ESWT is applied as soon as possible within 48 hours post-injury. | Device: Shock waves<br>* The shockwave generator orthogold 100® generates high-energy acoustic waves that behave much like other sound waves except that they have much greater pressure and energy. As with sound waves, Spark Waves® can easily travel great distance as long as the acoustic impedance stays the same.<br>|
| Sham Comparator: Control<br>In the control group, the same procedure is performed, but without the device emitting extracorporeal shock waves using a dummy head. | Device: dummy head<br>* The shockwave generator orthogold 100® will be used in combination with a dummy head, to Refrain shock waves<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in total motor scores (TMSC) = TMSC after 6 month minus TMSC at baseline | greater improvement in motor and sensory function (the AIS grade) can be achieved in patients after spinal trauma (AIS A-D) by applying a single extracorporeal shockwave therapy compared to the control group. | day 0 to 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| American Spinal Injury Association (ASIA) Impaiment Scale (AIS) grade | the AIS grade ranges from AIS A to AIS D, whereby AIS A are complete lesions and AIS B-D represent incomplete lesions | day 0 to 6 month | 
| degree of spasticity | self-rated degree of spasticity according to Penn Spasm Frequency Scale (PSFS); the scale ranges from 0 to 4, whereby 0 refers to no spasticity and 4 refers to more than 10 spasms per hour | day 0 to 6 month | 
| Walking ability (yes/no) | walking ability is being assessed using different walking tests as part of standard clinical routine: Walking Index for Spinal Cord Injury (WISCI) II, Timed up and go test (TUG), 10 Meter-Timed-Walk, 6 Minute-Walk-Test | day 0 to 6 month | 
| Urological function | Urological function will be assessed by several questions which should be answered with yes or no: Permanent catheter: yes/no Sensation of urinary bladder filling: yes/no Documentation of the first attempt of bladder emptying: pos/neg, date Self-catheterization: yes/no Do you feel sensory innervation of the external genitalia (penis / labia)? Do you feel the change of the catheter or manipulations on the catheter? Do you feel the urge to defecate? Do you feel stool evacuation? Male patients: Have you had an erection since your injury? Female patients: Have you felt sexually aroused since your injury? | day 0 to 6 month | 
| Plantar reflex (left/right: yes/no) | The plantar reflex (also called Babinski Test) will be performed separately on each foot to assess if pathological reflexes are present. | day 0 to 6 month | 
| Independence in everyday life | of patients is assessed with the Spinal Cord Independence Measure (SCIM II) | day 0 to 6 month | 
| adverse events (AEs) | The number of study related adverse events (AEs) are measured according to NCI CTCAE, version 5.0. | day 0 to 21 days | 
| Nine-Hole Peg Test (NHPT) (if feasible) | An evaluation of hand motor function is assessed in those patients who have their lesions above the level T5 | day 0 to 6 month | 
| Grasp and Release Test (GRT) | An evaluation of hand motor function is assessed in those patients who have their lesions above the level T5 | day 0 to 6 month | 
| Pinch grip: yes/no | An evaluation of hand motor function is assessed in those patients who have their lesions above the level T5 | day 0 to 6 month | 
| Clenched grip: yes/no | An evaluation of hand motor function is assessed in those patients who have their lesions above the level T5 | day 0 to 6 month | 
| Pencil grip: yes/no | An evaluation of hand motor function is assessed in those patients who have their lesions above the level T5 | day 0 to 6 month | 
| Lumbrical grip: yes/no | An evaluation of hand motor function is assessed in those patients who have their lesions above the level T5 | day 0 to 6 month |