Extracorporal Shock Wave Treatment to Improve Nerve Regeneration

Extracorporal Shock Wave Treatment After Microsurgical Coaptation to Improve Nerve Regeneration

This study evaluates the impact of extracorporeal shock wave treatment after microsurgical coaptation of finger nerves. Participants will be randomized into two treatment groups with different settings and a sham group. The participants will thereafter followed-up in a prospective, double-blind study design.

Study Overview

• Status: Recruiting
• Conditions: Peripheral Nerve Injury
• Intervention / Treatment: Device: Sham; Device: MTS Medical UG Orthogold 100

Detailed Description

Extracorporeal shock wave treatment is CE certified in Austria, Europe and licensed for indications like achillodynia, epicondylitis, or tendinitis calcanea. The Orthogold 100 device by MTS Medical UG will be used for this study.

Defocused low-energy extracorporeal shock wave therapy (ESWT) has gained acceptance as a therapeutic tool in different medical settings. It has been shown, that shock waves stimulate of the metabolic activity of different cell type, including osteoblasts, tenocytes, endothelial cells and chondrocytes. Furthermore, it has proved effective in clinical applications relating to bone and wound healing and myocardial ischaemia. Until now, no studies have been performed regarding the effects of ESWT on regeneration of peripheral nerve injuries in humans.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rudolf Rosenauer, M.D.; Phone Number: 0043 59393 41270; Email: rudolf.rosenauer@auva.at

Study Locations

• Austria
  • Vienna, Austria, 1120
    • Recruiting
    • Meidling Trauma Hospital
    • Contact: Rainer Mittermayr, M.D.; Phone Number: 0043 5 939345263; Email: rainer.mittermayr@auva.at
    • Principal Investigator: Rainer Mittermayr, M.D.
  • Vienna, Austria, 1200
    • Recruiting
    • Lorenz Böhler Trauma Hospital
    • Contact: Rudolf Rosenauer, M.D.; Phone Number: 0043 59393 41270; Email: rudolf.rosenauer@auva.at
    • Contact: Stefan Quadlbauer, M.D.; Phone Number: 0043 59393 41000; Email: stefan.quadlbauer@auva.at
    • Principal Investigator: Rudolf Rosenauer, M.D.
    • Sub-Investigator: Stefan Quadlbauer, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• complete lossless transection of one or more digital nerves distal to the branching out of the commune median or ulnar nerves
• direct, tension-free coaptation of the nerve stumps

Exclusion Criteria:

• segment loss of the nerve
• tension after direct coaptation
• diabetic neuropathy or other peripheral neuropathies
• other disease with reduced sensibility of the fingers
• injuries in the course of the nerve (plexus brachialis, median or ulnar nerve)
• chronic inflammatory disease
• rheumatoid arthritis
• pregnancy
• patients not able to give written consent
• patients with an implantable cardiac defibrillator or pacemaker
• patients which are sensitive to electromagnetic radiance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
SHAM_COMPARATOR: Sham	Device: Sham; Extracorporeal shock wave treatment will be faked.
ACTIVE_COMPARATOR: Shockwave 300 pulses; 300 pulses of extracorporeal shock wave will be applied	Device: MTS Medical UG Orthogold 100; 300 or 500 pulses, frequency 3Hz, energy 1 (0,1mJ/mm2)
ACTIVE_COMPARATOR: Shockwave 500 pulses; 500 pulses of extracorporeal shock wave will be applied	Device: MTS Medical UG Orthogold 100; 300 or 500 pulses, frequency 3Hz, energy 1 (0,1mJ/mm2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Two Point Discrimination	Two Point Discrimination distal of the nerve lesion in mm	1 year
Semmes Weinstein Monofilament test	Palpable Monofilaments, measured in Newton	1 year
Pain/Discomfort	0=Hinders function 1=Disturbing 2=Moderate 3=None/minor	1 year
hyperesthesia	0=Hinders function 1=Disturbing 2=Moderate 3=None/minor	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tinel Hoffmann sign	Progression of TH sign into the periphery	1 year
Sonography	sonography of the coaptation neuroma, measurement of the maximum diameter in mm	1 year
velocity of nerve conduction	Determination of velocity of nerve conduction	1 year
Medical Research Council Grading of Sensibility	Grading by the british medical research council. S0: No recovery of sensibility S1: Deep cutaneous pain sensibility S1+: superficial pain sensibility S2: superficial pain and some touch sensibility S2+: As in S2 but with overresponse S3: Pain and touch sensibility with over response, 2PD > 15mm S3+: As S3 but with imperfect recovery of 2PD (7-15mm) S4: Complete recovery	1 year

Collaborators and Investigators

• Sponsor: Ludwig Boltzmann Gesellschaft

Publications and helpful links

General Publications

• Bosch G, Lin YL, van Schie HT, van De Lest CH, Barneveld A, van Weeren PR. Effect of extracorporeal shock wave therapy on the biochemical composition and metabolic activity of tenocytes in normal tendinous structures in ponies. Equine Vet J. 2007 May;39(3):226-31. doi: 10.2746/042516407x180408.
• Corson MA, James NL, Latta SE, Nerem RM, Berk BC, Harrison DG. Phosphorylation of endothelial nitric oxide synthase in response to fluid shear stress. Circ Res. 1996 Nov;79(5):984-91. doi: 10.1161/01.res.79.5.984.
• Fleming I, Bauersachs J, Fisslthaler B, Busse R. Ca2+-independent activation of the endothelial nitric oxide synthase in response to tyrosine phosphatase inhibitors and fluid shear stress. Circ Res. 1998 Apr 6;82(6):686-95. doi: 10.1161/01.res.82.6.686.
• Fukumoto Y, Ito A, Uwatoku T, Matoba T, Kishi T, Tanaka H, Takeshita A, Sunagawa K, Shimokawa H. Extracorporeal cardiac shock wave therapy ameliorates myocardial ischemia in patients with severe coronary artery disease. Coron Artery Dis. 2006 Feb;17(1):63-70. doi: 10.1097/00019501-200602000-00011.
• Hausdorf J, Sievers B, Schmitt-Sody M, Jansson V, Maier M, Mayer-Wagner S. Stimulation of bone growth factor synthesis in human osteoblasts and fibroblasts after extracorporeal shock wave application. Arch Orthop Trauma Surg. 2011 Mar;131(3):303-9. doi: 10.1007/s00402-010-1166-4. Epub 2010 Aug 22.
• Martini L, Giavaresi G, Fini M, Torricelli P, de Pretto M, Schaden W, Giardino R. Effect of extracorporeal shock wave therapy on osteoblastlike cells. Clin Orthop Relat Res. 2003 Aug;(413):269-80. doi: 10.1097/01.blo.0000073344.50837.cd.
• Moretti B, Notarnicola A, Garofalo R, Moretti L, Patella S, Marlinghaus E, Patella V. Shock waves in the treatment of stress fractures. Ultrasound Med Biol. 2009 Jun;35(6):1042-9. doi: 10.1016/j.ultrasmedbio.2008.12.002. Epub 2009 Feb 25.
• Moretti B, Notarnicola A, Maggio G, Moretti L, Pascone M, Tafuri S, Patella V. The management of neuropathic ulcers of the foot in diabetes by shock wave therapy. BMC Musculoskelet Disord. 2009 May 27;10:54. doi: 10.1186/1471-2474-10-54.
• Murata R, Nakagawa K, Ohtori S, Ochiai N, Arai M, Saisu T, Sasho T, Takahashi K, Moriya H. The effects of radial shock waves on gene transfer in rabbit chondrocytes in vitro. Osteoarthritis Cartilage. 2007 Nov;15(11):1275-82. doi: 10.1016/j.joca.2007.04.001. Epub 2007 May 29.
• Nishida T, Shimokawa H, Oi K, Tatewaki H, Uwatoku T, Abe K, Matsumoto Y, Kajihara N, Eto M, Matsuda T, Yasui H, Takeshita A, Sunagawa K. Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo. Circulation. 2004 Nov 9;110(19):3055-61. doi: 10.1161/01.CIR.0000148849.51177.97. Epub 2004 Nov 1.
• Schaden W, Fischer A, Sailler A. Extracorporeal shock wave therapy of nonunion or delayed osseous union. Clin Orthop Relat Res. 2001 Jun;(387):90-4. doi: 10.1097/00003086-200106000-00012.
• Schaden W, Thiele R, Kolpl C, Pusch M, Nissan A, Attinger CE, Maniscalco-Theberge ME, Peoples GE, Elster EA, Stojadinovic A. Shock wave therapy for acute and chronic soft tissue wounds: a feasibility study. J Surg Res. 2007 Nov;143(1):1-12. doi: 10.1016/j.jss.2007.01.009. Epub 2007 Sep 27.
• Zimpfer D, Aharinejad S, Holfeld J, Thomas A, Dumfarth J, Rosenhek R, Czerny M, Schaden W, Gmeiner M, Wolner E, Grimm M. Direct epicardial shock wave therapy improves ventricular function and induces angiogenesis in ischemic heart failure. J Thorac Cardiovasc Surg. 2009 Apr;137(4):963-70. doi: 10.1016/j.jtcvs.2008.11.006.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 18, 2017
• Primary Completion (ANTICIPATED): April 1, 2023
• Study Completion (ANTICIPATED): June 1, 2023

Study Registration Dates

• First Submitted: April 21, 2017
• First Submitted That Met QC Criteria: May 9, 2017
• First Posted (ACTUAL): May 10, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 5, 2021
• Last Update Submitted That Met QC Criteria: September 3, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: extracorporeal shock wave; nerve regeneration; microsurgical nerve coaptation
• Additional Relevant MeSH Terms: Nervous System Diseases; Wounds and Injuries; Neuromuscular Diseases; Peripheral Nervous System Diseases; Trauma, Nervous System; Peripheral Nerve Injuries
• Other Study ID Numbers: MPG 07/2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No