Chitosan Nerv Tube for Primary Repair of Traumatic Sensory Nerve Lesions of the Hand

Traumatic Lesion of Sensory Nerves of the Hand Clinical Trial

— CNT  

Official title:

Chitosan Nerv Tube for Primary Repair of Traumatic Sensory Nerve Lesions of the Hand - a Clinical Randomized Controlled Multicenter Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02372669
• Other study ID #: BGU-LU-123
• Status: Recruiting
• Phase: N/A
• First received: February 15, 2015
• Last updated: July 11, 2017
• Start date: March 2015
• Est. completion date: September 2018

Study information

• Verified date: July 2017
• Source: BG Unfallklinik
• Contact: Florian Neubrech, MD
• Phone: +49-0621-8906
• Email: florian.neubrech[@]bgu-ludwigshafen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to evaluate whether the additional use of a nerve tube in primary microsurgical repair of traumatic sensory nerve lesions of the hand has an effect on convalescence and functional results.

Description:

Standard therapy for nerve injuries of the hand without a gap is a direct tension free microsurgical repair. Often, a nerve tube is used in addition to a direct nerve suture to protect the nerve from scar formation and guide the regenerating axons to the distal stump, but there is still a lack of data for this approach. The basic design of these nerve tubes is similar but they are made of different resorbable biomaterials. Chitosan, a derivative of chitin, is biocompatible and is similar to natural glycosaminoglycans. In vivo studies showed positive effects on the survival and orientation of Schwann cells as well as the survival and differentiation of neuronal cells and prevention of painful neuromas. Therefore it is the ideal material for a nerve tube. In this study we want to test a Chitosan based nerve tube (already certified German medical product with European label (CE-label)) - as an additional treatment for digital nerve injuries without a gap.

This study will enroll participants with traumatic sensory nerve lesions from 3 Centres:

Trauma Center Ludwigshafen (Ludwigshafen, Germany), Trauma Center Frankfurt am Main (Frankfurt am Main, Germany) and Trauma Center Bochum (Bochum, Germany). After being informed about the study and its potential risks, patients with traumatic sensory nerve lesions will be consecutively screened for eligibility. The study will be conducted in four successive periods. All enrolled participants will be randomized locally by alternating local lists in the Double-Blind Period. After enrolment, the assigned subject number will be used on all Case Report Forms. The kind of intervention is blinded for the participant and for the investigator of the follow-up that was not involved in surgery. Enrolled participants will be randomized in a 1:1 ratio to primary microsurgical repair with the additional use of a nerve tube, or direct tension free microsurgical repair alone.

Data will be collected in Case Report Forms (CRFs) according to European DIN standard (International Standards Organization (EN ISO) 14155) and Good Clinical Practice recommendations. CRFs will be transmitted electronically to the executive study centre in Ludwigshafen and will be checked there for integrity, quality and consistency. The executive study centre will also ensure standardisation of the registry process, operative procedure and follow-up in all participating centers by periodic monitoring. Furthermore written instructions and a course of instruction will be provided to each Investigator. Data will be collected and analyzed in the executive study centre. There will be also CRFs for reporting drop-outs and for reporting adverse events.

The static 2-point-discrimination (2PD) after 6 months will bet the primary outcome parameter. Assumptions for the gold standard treatment can be made from literature. The mean of 2-PD after 6 months is approximately 8 mm with a standard deviation of 3 mm. A decrease of 2 mm in the 2-PD would be clinically relevant and is assumed for the experimental intervention. Using a 2-sided t-test with a level of 0.05 and a power of 80%, will require 37 patients per group in order to show superiority. The primary endpoint is tested in the per-protocol set (PPS) via an analysis of covariance with centre as factor and distance between lesion and finger pulp as covariate. Secondary objectives will be described without confirmatory analysis. In order to compensate a loss of follow-up or data 50 patients per group will be randomized.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 2018
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 67 Years

Eligibility

Inclusion Criteria:

• Primary complete traumatic lesion of sensory-only nerves of the hand without a defect zone

• Patient age between 18 an 67 years

• Informed Consent.

Exclusion Criteria:

• Amputated or avascular fingers

• Known impaired sensibility of the injured finger

• Allergy to chitosan

• Pregnancy

• Immunodeficiency

Related Conditions & MeSH terms

• Traumatic Lesion of Sensory Nerves of the Hand

Intervention

Device:
• Chitosan nerve tube in addition to gold standard therapy
Primary microsurgical repair of traumatic lesion of sensory nerves of the hand with use of an chitosan nerve tube in addition. Clinical Follow-up will be performed after 3,6,12 and 24 months.

Procedure:
• Gold standard Primary microsurgical repair
Primary microsurgical repair of traumatic lesion of sensory nerves of the hand. Clinical Follow-up will be performed after 3,6,12 and 24 months.

Locations

Country	Name	City	State
Germany	BG Universitätsklinikum Bergmannsheil Bochum	Bochum
Germany	BG Unfallklinik Frankfurt	Frankfurt
Germany	BG Unfallklinik Ludwigshafen	Ludwigshafen

Sponsors (1)

Lead Sponsor	Collaborator
BG Unfallklinik

Country where clinical trial is conducted

Germany, 

References & Publications (17)

Ao Q, Fung CK, Tsui AY, Cai S, Zuo HC, Chan YS, Shum DK. The regeneration of transected sciatic nerves of adult rats using chitosan nerve conduits seeded with bone marrow stromal cell-derived Schwann cells. Biomaterials. 2011 Jan;32(3):787-96. doi: 10.1016/j.biomaterials.2010.09.046. Epub 2010 Oct 14. — View Citation

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Chaise F, Friol JP, Gaisne E. [Results of emergency repair of wounds of palmar collateral nerves of the fingers]. Rev Chir Orthop Reparatrice Appar Mot. 1993;79(5):393-7. French. — View Citation

Freier T, Koh HS, Kazazian K, Shoichet MS. Controlling cell adhesion and degradation of chitosan films by N-acetylation. Biomaterials. 2005 Oct;26(29):5872-8. Epub 2005 Apr 9. — View Citation

Haastert-Talini K, Geuna S, Dahlin LB, Meyer C, Stenberg L, Freier T, Heimann C, Barwig C, Pinto LF, Raimondo S, Gambarotta G, Samy SR, Sousa N, Salgado AJ, Ratzka A, Wrobel S, Grothe C. Chitosan tubes of varying degrees of acetylation for bridging peripheral nerve defects. Biomaterials. 2013 Dec;34(38):9886-904. doi: 10.1016/j.biomaterials.2013.08.074. Epub 2013 Sep 17. — View Citation

Hudak PL, Amadio PC, Bombardier C. Development of an upper extremity outcome measure: the DASH (disabilities of the arm, shoulder and hand) [corrected]. The Upper Extremity Collaborative Group (UECG). Am J Ind Med. 1996 Jun;29(6):602-8. Erratum in: Am J Ind Med 1996 Sep;30(3):372. — View Citation

Kim DH, Han K, Tiel RL, Murovic JA, Kline DG. Surgical outcomes of 654 ulnar nerve lesions. J Neurosurg. 2003 May;98(5):993-1004. — View Citation

Konofaos P, Ver Halen JP. Nerve repair by means of tubulization: past, present, future. J Reconstr Microsurg. 2013 Mar;29(3):149-64. doi: 10.1055/s-0032-1333316. Epub 2013 Jan 9. Review. — View Citation

Lewin-Kowalik J, Marcol W, Kotulska K, Mandera M, Klimczak A. Prevention and management of painful neuroma. Neurol Med Chir (Tokyo). 2006 Feb;46(2):62-7; discussion 67-8. Review. — View Citation

Marcol W, Larysz-Brysz M, Kucharska M, Niekraszewicz A, Slusarczyk W, Kotulska K, Wlaszczuk P, Wlaszczuk A, Jedrzejowska-Szypulka H, Lewin-Kowalik J. Reduction of post-traumatic neuroma and epineural scar formation in rat sciatic nerve by application of microcrystallic chitosan. Microsurgery. 2011 Nov;31(8):642-9. doi: 10.1002/micr.20945. Epub 2011 Oct 18. — View Citation

Meek MF, Coert JH. Recovery of two-point discrimination function after digital nerve repair in the hand using resorbable FDA- and CE-approved nerve conduits. J Plast Reconstr Aesthet Surg. 2013 Oct;66(10):1307-15. doi: 10.1016/j.bjps.2013.04.058. Epub 2013 Jul 2. Review. — View Citation

Scott J, Huskisson EC. Vertical or horizontal visual analogue scales. Ann Rheum Dis. 1979 Dec;38(6):560. — View Citation

Simões MJ, Gärtner A, Shirosaki Y, Gil da Costa RM, Cortez PP, Gartnër F, Santos JD, Lopes MA, Geuna S, Varejão AS, Maurício AC. In vitro and in vivo chitosan membranes testing for peripheral nerve reconstruction. Acta Med Port. 2011 Jan-Feb;24(1):43-52. Epub 2011 Feb 28. — View Citation

Weber RA, Breidenbach WC, Brown RE, Jabaley ME, Mass DP. A randomized prospective study of polyglycolic acid conduits for digital nerve reconstruction in humans. Plast Reconstr Surg. 2000 Oct;106(5):1036-45; discussion 1046-8. — View Citation

Xu H, Yan Y, Li S. PDLLA/chondroitin sulfate/chitosan/NGF conduits for peripheral nerve regeneration. Biomaterials. 2011 Jul;32(20):4506-16. doi: 10.1016/j.biomaterials.2011.02.023. Epub 2011 Mar 11. — View Citation

Yuan Y, Zhang P, Yang Y, Wang X, Gu X. The interaction of Schwann cells with chitosan membranes and fibers in vitro. Biomaterials. 2004 Aug;25(18):4273-8. — View Citation

Zimmermann M. Pathobiology of neuropathic pain. Eur J Pharmacol. 2001 Oct 19;429(1-3):23-37. Review. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events	Record of any type of revision surgery. Registration of the incidence of postoperative hematoma, deep wound infections, disturbances of scar formation.	Participants will be followed for the duration of hospital stay, an expected average of 5 days and 3,6,12,24 months after intervention.
Primary	Ability for two-point discrimination of the injured finger (2PD) (measured with compasses0	The ability for static two-point discrimination of the injured finger will be measured with compasses in the 6 month follow-up.	6 months after intervention
Secondary	Ability for two-point discrimination of the injured finger (2PD) / Sensibility (checking patients ability to recognize filaments of different calibers.)	The ability for static two-point discrimination of the injured finger will be measured with compasses also in the other follow-ups. Furthermore, sensibility of the injured finger will be measured by	3,6,12,24 months after intervention
Secondary	DASH-score	Patient`s individual disability in activities of daily living will be measured with the DASH-questionnaire.	3,6,12,24 months after intervention
Secondary	Grip strength	Grip strength of both hands will be measured with a dynamometer and will be compared to the opposite side.	3,6,12,24 months after intervention
Secondary	Range of motion of the injured finger	The Range of motion of the injured finger will be measured with a goniometer for small joints and will be compared to the opposite side.	3,6,12,24 months after intervention
Secondary	Pain (visual analogue scales)	Patients will self report pain on visual analogue scales, ranged from 0 (no pain) up to 10 (maximum of pain)	3,6,12,24 months after intervention
Secondary	Cold intolerance (Grades: 0 = Hinders function; 1 = Disturbing; 2 = Moderate; 3 = None/minor)	The examiner will question the patient about cold intolerance. (Grades: 0 = Hinders function; 1 = Disturbing; 2 = Moderate; 3 = None/minor)	3,6,12,24 months after intervention
Secondary	Hypersensitivity (Grades: 0 = Hinders function; 1 = Disturbing; 2 = Moderate; 3 = None/minor)	The examiner will stroke the dysfunctional area and question the patient about cold hypersensitivity. (Grades: 0 = Hinders function; 1 = Disturbing; 2 = Moderate; 3 = None/minor)	3,6,12,24 months after intervention
Secondary	Existence of neuromas	The existence of a neuroma will be assessed clinically and by neurosonography.	3,6,12,24 months after intervention