Clinical trial NCT04474106: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Traumatic Spinal Cord Injury
Lead sponsor: AUVA
Sponsor class: OTHER
First posted: 2020-07-16
Enrollment: 246
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two-arm three-stage adaptive, prospective, multi-center, randomized, double-blind, placebo-controlled clinical trial
Primary purpose: TREATMENT

Brief summary: 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.


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

Primary outcomes:
measure: changes in total motor scores (TMSC) = TMSC after 6 month minus TMSC at baseline
timeFrame: day 0 to 6 month
Secondary outcomes:
measure: American Spinal Injury Association (ASIA) Impaiment Scale (AIS) grade
timeFrame: day 0 to 6 month
measure: degree of spasticity
timeFrame: day 0 to 6 month
measure: Walking ability (yes/no)
timeFrame: day 0 to 6 month
measure: Urological function
timeFrame: day 0 to 6 month
measure: Plantar reflex (left/right: yes/no)
timeFrame: day 0 to 6 month
measure: Independence in everyday life
timeFrame: day 0 to 6 month
measure: adverse events (AEs)
timeFrame: day 0 to 21 days
measure: Nine-Hole Peg Test (NHPT) (if feasible)
timeFrame: day 0 to 6 month
measure: Grasp and Release Test (GRT)
timeFrame: day 0 to 6 month
measure: Pinch grip: yes/no
timeFrame: day 0 to 6 month
measure: Clenched grip: yes/no
timeFrame: day 0 to 6 month
measure: Pencil grip: yes/no
timeFrame: day 0 to 6 month
measure: Lumbrical grip: yes/no
timeFrame: day 0 to 6 month
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
state: Tirol
city: Bad Häring
country: Austria
facility: Rehazentrum Bad Häring
city: Feldkirch
country: Austria
facility: Landeskarnkenhaus Feldkirch
city: Graz
country: Austria
facility: Unfallkrankenhaus Graz
city: Graz
country: Austria
facility: Rehazentrum Tobelbad
city: Klagenfurt
country: Austria
facility: Unfallkrankenhaus Klagenfurt
city: Klosterneuburg
country: Austria
facility: Rehazentrum Weißer Hof
city: Linz
country: Austria
facility: Unfallkrankenhaus Linz
city: Salzburg
country: Austria
facility: Unfallkrankenhaus Salzburg
city: Salzburg
country: Austria
facility: Universitätsklinik für Orthopädie und Traumatologie
city: St. Pölten
country: Austria
facility: Unfallkrankenhaus St. Pölten
city: Wien
country: Austria
facility: Universitätsklinik Wien, AKH
city: Wien
country: Austria
facility: Unfallkrankenhaus Meidling
city: Wien
country: Austria
facility: Unfallkrankenhaus Lorenz Böhler
city: Wien
country: Austria
facility: SMZ Ost, Donauspital Abteilung für Unfallchirurgie
Study officials:
affiliation: AUVA
name: Wolfgang Schaden, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 trial. Trials. 2022 Apr 1;23(1):245. doi: 10.1186/s13063-022-06161-8.