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

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

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.

Study Overview

• Status: Unknown
• Conditions: Traumatic Lesion of Sensory Nerves of the Hand
• Intervention / Treatment: Device: Chitosan nerve tube in addition to gold standard therapy; Procedure: Gold standard Primary microsurgical repair

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Florian Neubrech, MD; Phone Number: +49-0621-8906; Email: florian.neubrech@bgu-ludwigshafen.de
• Study Contact Backup: Name: Thomas Kremer, MD; Phone Number: +49-0621-8913; Email: thomas.kremer@bgu-ludwigshafen.de

Study Locations

• Germany
  • Bochum, Germany
    • Recruiting
    • BG Universitätsklinikum Bergmannsheil Bochum
    • Contact: Adrien Daigeler, MD; Phone Number: +49-0234-302-3364; Email: adrien.daigeler@bergmannsheil.de
  • Frankfurt, Germany
    • Recruiting
    • BG Unfallklinik Frankfurt
    • Contact: Michael Sauerbier, MD; Phone Number: +49-069-475-2021; Email: michael.sauerbier@bgu-frankfurt.de
  • Ludwigshafen, Germany
    • Recruiting
    • BG Unfallklinik Ludwigshafen
    • Contact: Florian Neubrech, MD; Phone Number: +49-0621-6810-8906; Email: florian.neubrech@bgu-ludwigshafen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 67 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chitosan; Enrolled participants presenting with traumatic sensory nerve lesions of the hand without defect zone that were randomized to primary microsurgical repair with the additional use of a chitosan nerve tube.	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.
Active Comparator: Gold standard alone; Enrolled participants presenting with traumatic sensory nerve lesions of the hand without defect zone that were randomized to primary microsurgical repair without the additional use of a chitosan nerve tube.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
Existence of neuromas	The existence of a neuroma will be assessed clinically and by neurosonography.	3,6,12,24 months after intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: BG Unfallklinik
• Investigators: Study Chair: Thomas Kremer, MD, BG Unfallklinik Ludwigshafen

Publications and helpful links

General Publications

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• Neubrech F, Heider S, Harhaus L, Bickert B, Kneser U, Kremer T. Chitosan nerve tube for primary repair of traumatic sensory nerve lesions of the hand without a gap: study protocol for a randomized controlled trial. Trials. 2016 Jan 26;17:48. doi: 10.1186/s13063-015-1148-5.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): July 1, 2017
• Study Completion (Anticipated): September 1, 2018

Study Registration Dates

• First Submitted: February 15, 2015
• First Submitted That Met QC Criteria: February 25, 2015
• First Posted (Estimate): February 26, 2015

Study Record Updates

• Last Update Posted (Actual): July 13, 2017
• Last Update Submitted That Met QC Criteria: July 11, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hemostatics; Coagulants; Chelating Agents; Sequestering Agents; Chitosan
• Other Study ID Numbers: BGU-LU-123