search
Back to results

Nerve Repair Using Hydrophilic Polymers to Promote Immediate Fusion of Severed Axons and Swift Return of Function

Primary Purpose

Peripheral Nerve Injury

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Polyethylene glycol (PEG)
Sponsored by
Vanderbilt University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peripheral Nerve Injury

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of a Sunderland Class 5 traumatic neuropathy (transection injury) of a digital nerve in the upper extremity
  • candidates for immediate operative repair (Arm 1);
  • injury proceeding repair no longer than 72 hours; and
  • repair within 48 hours of injury that require nerve grafting;
  • N0 significant medical comorbidities precluding immediate repair;
  • willing to comply with all aspects of the treatment and evaluation schedule over a 12 months period.

We plan to include subjects who have peripheral nerve injuries that are complicated by significant vascular or orthopedic damage.

Exclusion Criteria:

  • Patients will be excluded from enrollment if their injuries exhibit gross contamination, in circumstances where soft tissue coverage is inadequate, or when staged repair is planned.
  • We will also exclude patients that are diabetic, have been diagnosed with a neuromuscular disease, or are undergoing chemotherapy, radiation therapy, or other treatments known to affect the growth of the neural and vascular system.
  • We will exclude all patients currently enrolled in another investigational study or those who are unlikely to complete the normal regime of occupational therapy. Individuals will be excluded from participation if their time of injury falls outside study parameters.

Sites / Locations

  • Vanderbilt University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

No Intervention

No Intervention

No Intervention

Experimental

Experimental

Experimental

Arm Label

standard epineural repair <24 hours

standard epineural repair >24 - 72 hours

epineural repair with autografting within 48 hours

epineural repair <24 hours using PEG

epineural repair >24 but <72 hours using PEG

epineural repair with autografting within 48 hours, using PEG

Arm Description

epineural repair following treatment with standard epineural repair alone in sensory nerve injuries in the upper extremity in short-term acute injuries (repaired <24 hours after injury); no medication used

epineural repair following irrigation with standard epineural repair alone in sensory nerve injuries in the upper extremity in short-term chronic injuries (>24-<72 hours after injury); no medication used

epineural repair with auto grafting within 48 hours; no medication used

epineural repair following treatment with standard epineural repair using PEG in sensory nerve injuries in the upper extremity in short-term acute injuries (repaired <24 hours after injury); PEG is used during the surgical procedure

epineural repair following treatment with standard epineural repair using PEG in sensory nerve injuries in the upper extremity in short-term acute injuries (repaired >24 hours but < 72 hours after injury); PEG is used during the surgical procedure

epineural repair with auto grafting within 48 hours

Outcomes

Primary Outcome Measures

return of nerve function as measured by (Medical Research Council Classificatoin (MRCC)
Medical Research Council Classificatoin (MRCC)

Secondary Outcome Measures

Full Information

First Posted
February 4, 2015
Last Updated
November 26, 2022
Sponsor
Vanderbilt University
search

1. Study Identification

Unique Protocol Identification Number
NCT02359825
Brief Title
Nerve Repair Using Hydrophilic Polymers to Promote Immediate Fusion of Severed Axons and Swift Return of Function
Official Title
Nerve Repair Using Hydrophilic Polymers to Promote Immediate Fusion of Severed Axons and Swift Return of Function
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 2015 (undefined)
Primary Completion Date
July 2025 (Anticipated)
Study Completion Date
July 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Current strategies for peripheral nerve repair are severely limited. Even with current techniques, it can take months for regenerating axons to reach denervated target tissues when injuries are proximally located. This inability to rapidly restore the loss of function after axonal injury continues to produce poor clinical outcomes. The investigators propose testing the efficacy and safety of a combination therapy: polyethylene glycol (PEG) assisted axonal fusion technique to repair peripheral nerve injuries in humans.
Detailed Description
Our own preclinical animal studies have been designed to take advantage of PEG. We have used the fusogenic properties of PEG and this has allowed us to demonstrate a rapid and decisive electrophysiological recovery of either crushed or completely severed sciatic nerves in a commonly accepted mammalian model for peripheral nerve injury (Bittner et al JSR 2012). Recently, we modified previously published mammalian techniques. Our goal was to eliminate laboratory solutions that have not been approved for use in humans and replace them with readily available reagents commonly used in clinical applications. PEG is commercially available in many molecular formulations and our earlier experiments with PEG having a molecular weight of 2 kD. Unfortunately, this molecular weight is not approved by the Food and Drug Administration (FDA) for human usage. In our more recent preclinical studies, we have demonstrated that PEG 3.35 kD, the main ingredient in the commonly used cathartic known as MiraLAX© (MERCK; Whitehouse Station, NJ), actually generates superior fusion over PEG 2KD in a cut nerve model. Thus the clinical trial that forms the basis of this proposal was developed with the FDA approved 3.35 kD PEG and these other two FDA approved solutions. Additional studies in our complex nerve injury model have also demonstrated that the repair does not have to be performed immediately after nerve injury. Epineural repair with PEG 3.35 kD treatment can be performed up to 24hrs after injury and postoperative CAPs are obtained in all PEG 3.35 kD treated animals (n=3, data not shown). The remarkable finding is that in the 24-hour injury model, PEG significantly improves behavioral outcome measured at 72 hours postoperatively. Based on the published reports and our own in vivo studies, we demonstrate that PEG based repair can restore CAPs immediately and improve functional recovery significantly post injury. These preclinical findings suggest that we can offer a novel therapy to test in humans who have experienced complete transection of a peripheral nerve. Patient risk is minimized as we have optimized the PEG facilitated fusion technique to utilize commonly used FDA approved drugs, solutions and electrolytes to augment standard neurorrhaphy techniques. The experimental protocol entails 100% transection injury to a peripheral nerve followed by a standard neurorrhaphy. The repair is then irrigated gently with PEG for two minutes and sterile water in standard fashion is used to wash away the PEG. The most likely scenarios, that explain rapid compound action potential (CAP) restoration, are the rapid restoration of cytoplasmic flow within the nerves, the rapid ability of membranes to depolarize and possibly the prevention of Wallerian degeneration.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Nerve Injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
standard epineural repair <24 hours
Arm Type
No Intervention
Arm Description
epineural repair following treatment with standard epineural repair alone in sensory nerve injuries in the upper extremity in short-term acute injuries (repaired <24 hours after injury); no medication used
Arm Title
standard epineural repair >24 - 72 hours
Arm Type
No Intervention
Arm Description
epineural repair following irrigation with standard epineural repair alone in sensory nerve injuries in the upper extremity in short-term chronic injuries (>24-<72 hours after injury); no medication used
Arm Title
epineural repair with autografting within 48 hours
Arm Type
No Intervention
Arm Description
epineural repair with auto grafting within 48 hours; no medication used
Arm Title
epineural repair <24 hours using PEG
Arm Type
Experimental
Arm Description
epineural repair following treatment with standard epineural repair using PEG in sensory nerve injuries in the upper extremity in short-term acute injuries (repaired <24 hours after injury); PEG is used during the surgical procedure
Arm Title
epineural repair >24 but <72 hours using PEG
Arm Type
Experimental
Arm Description
epineural repair following treatment with standard epineural repair using PEG in sensory nerve injuries in the upper extremity in short-term acute injuries (repaired >24 hours but < 72 hours after injury); PEG is used during the surgical procedure
Arm Title
epineural repair with autografting within 48 hours, using PEG
Arm Type
Experimental
Arm Description
epineural repair with auto grafting within 48 hours
Intervention Type
Drug
Intervention Name(s)
Polyethylene glycol (PEG)
Other Intervention Name(s)
PEG
Intervention Description
For the control groups, epineural repair or interposition grafting will be undertaken in the standard end-to-end fashion using interrupted nylon suture after irrigation of the wound with normal saline as deemed necessary by the operating surgeon. For the experimental group, the nerve(s) will be repaired using standard suture neurorrhaphy techniques and a 149.25 mM (50%) solution of PEG 3.35 kD in sterile water will then be irrigated onto the neurorrhaphy site for one minute. Following this, the approximated nerve ends will be irrigated with sterile water gently for 2 minutes. All wounds will be closed in the fashion deemed appropriate by the operating surgeon.
Primary Outcome Measure Information:
Title
return of nerve function as measured by (Medical Research Council Classificatoin (MRCC)
Description
Medical Research Council Classificatoin (MRCC)
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of a Sunderland Class 5 traumatic neuropathy (transection injury) of a digital nerve in the upper extremity candidates for immediate operative repair (Arm 1); injury proceeding repair no longer than 72 hours; and repair within 48 hours of injury that require nerve grafting; N0 significant medical comorbidities precluding immediate repair; willing to comply with all aspects of the treatment and evaluation schedule over a 12 months period. We plan to include subjects who have peripheral nerve injuries that are complicated by significant vascular or orthopedic damage. Exclusion Criteria: Patients will be excluded from enrollment if their injuries exhibit gross contamination, in circumstances where soft tissue coverage is inadequate, or when staged repair is planned. We will also exclude patients that are diabetic, have been diagnosed with a neuromuscular disease, or are undergoing chemotherapy, radiation therapy, or other treatments known to affect the growth of the neural and vascular system. We will exclude all patients currently enrolled in another investigational study or those who are unlikely to complete the normal regime of occupational therapy. Individuals will be excluded from participation if their time of injury falls outside study parameters.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wesley Thayer, MD
Phone
615-936-0160
Email
wesley.thayer@vanderbilt.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Julia Yao, BSN
Phone
615-343-8426
Email
jun.yao@vumc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wesley Thayer, MD
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

Nerve Repair Using Hydrophilic Polymers to Promote Immediate Fusion of Severed Axons and Swift Return of Function

We'll reach out to this number within 24 hrs