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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Traumatic Lesion of Sensory Nerves of the Hand

Intervention / Treatment
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* Device: Chitosan nerve tube in addition to gold standard therapy
* Procedure: Gold standard Primary microsurgical repair


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 67 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chitosan<br>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<br>* 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.<br>Procedure: Gold standard Primary microsurgical repair<br>* 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.<br>|
| Active Comparator: Gold standard alone<br>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<br>* 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.<br>|

What is the study measuring?
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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 |