Clinical trial NCT02359825: 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
Overall status: RECRUITING
Phase: PHASE1
Conditions: Peripheral Nerve Injury
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2015-02-10
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: return of nerve function as measured by (Medical Research Council Classificatoin (MRCC)
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Wesley Thayer, MD
role: PRINCIPAL_INVESTIGATOR
References: