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

Official title

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

Overview

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.

Interventions

• Device Shock waves
  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.
• Device dummy head
  The shockwave generator orthogold 100® will be used in combination with a dummy head, to Refrain shock waves

Primary outcome measures

• changes in total motor scores (TMSC) = TMSC after 6 month minus TMSC at baseline [Time frame: day 0 to 6 month]

Secondary outcome measures (12)

• American Spinal Injury Association (ASIA) Impaiment Scale (AIS) grade [Time frame: day 0 to 6 month]
• degree of spasticity [Time frame: day 0 to 6 month]
• Walking ability (yes/no) [Time frame: day 0 to 6 month]
• Urological function [Time frame: day 0 to 6 month]
• Plantar reflex (left/right: yes/no) [Time frame: day 0 to 6 month]
• Independence in everyday life [Time frame: day 0 to 6 month]
• adverse events (AEs) [Time frame: day 0 to 21 days]
• Nine-Hole Peg Test (NHPT) (if feasible) [Time frame: day 0 to 6 month]
• Grasp and Release Test (GRT) [Time frame: day 0 to 6 month]
• Pinch grip: yes/no [Time frame: day 0 to 6 month]
• Clenched grip: yes/no [Time frame: day 0 to 6 month]
• Pencil grip: yes/no [Time frame: day 0 to 6 month]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Austria · 15 centers

• Medical University Innsbruck — Innsbruck
• Rehazentrum Bad Häring — Bad Häring
• Landeskarnkenhaus Feldkirch — Feldkirch
• Unfallkrankenhaus Graz — Graz
• Rehazentrum Tobelbad — Graz
• Unfallkrankenhaus Klagenfurt — Klagenfurt
• Rehazentrum Weißer Hof — Klosterneuburg
• Unfallkrankenhaus Linz — Linz
• … and 7 more centers

Publications

• Nagele S, Zellmer B, Graber M, Winter-Polzl L, Engler C, Hirsch J, Schmidt S, Eder J, Lohmann R, Ioannou-Nikolaidou M, Heim V, Grimm M, Bonaros N, Gollmann-Tepekoylu C, Holfeld J, Nagele F. Current Preclinical and Clinical Evidence of Shock Wave Therapy for Spinal Cord Injury: A Systematic Review. Cells. 2026 Apr 13;15(8):687. doi: 10.3390/cells15080687. PMID 42041555
• Leister I, Mittermayr R, Mattiassich G, Aigner L, Haider T, Machegger L, Kindermann H, Grazer-Horacek A, Holfeld J, Schaden W. The effect of extracorporeal shock wave therapy in acute traumatic spinal cord injury on motor and sensory function within 6 months post-injury: a study protocol for a two-arm three-stage adaptive, prospective, multi-center, randomized, blinded, placebo-controlled clinical PMID 35365190

Identifiers

NCT: NCT04474106 · NEUROwave

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗