PEG Fusion Technique for Peripheral Nerve Injury

Overseen By Julia Yao, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Vanderbilt University

Must not be taking: Chemotherapy, Radiation

Disqualifiers: Diabetes, Neuromuscular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to 72 hours post-injury

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new technique called polyethylene glycol (PEG) fusion to repair peripheral nerve injuries more effectively. Current methods often result in slow nerve healing, especially in the upper body, leading to poor recovery. The trial aims to determine if using PEG during surgery accelerates and improves nerve healing. Individuals with a specific type of nerve injury in the arm or hand, sustained within the last few days and scheduled for surgery soon, might be suitable candidates for this study. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are undergoing treatments like chemotherapy or radiation therapy, you would be excluded from the trial.

What prior data suggests that this PEG fusion technique is safe for peripheral nerve injury repair?

Research has shown that polyethylene glycol (PEG) could be a helpful treatment for nerve injuries. Studies indicate that PEG can help nerves heal faster and more effectively. In animal studies, PEG prevented nerve damage and aided recovery. Although limited data exists on PEG's effects in humans, early studies suggest it is generally safe. This trial is in its early stages, indicating the treatment is considered safe enough for human testing. However, more research is needed to fully understand PEG's safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the PEG fusion technique for peripheral nerve injuries because it offers a promising new approach to healing. Unlike traditional methods, which typically rely on standard epineural repair or autografting alone, this technique uses polyethylene glycol (PEG) during surgical repair to potentially enhance nerve regeneration. PEG acts as a sort of "glue" to fuse nerve membranes together, which could improve recovery times and outcomes. This new approach might significantly reduce healing time and improve nerve function in cases where nerves have been injured, especially in the upper extremities.

What evidence suggests that the PEG fusion technique is effective for peripheral nerve injury?

Research has shown that polyethylene glycol (PEG), which participants in this trial may receive, can help treat nerve injuries. Studies have found that PEG greatly improves and speeds up nerve healing, especially in cases like sciatic nerve damage. Evidence indicates that PEG-fusion leads to quick and noticeable recovery in nerve injuries, particularly in early research models. Compared to standard treatments, PEG has demonstrated benefits in improving recovery after nerve damage. This trial will compare different approaches using PEG, such as epineural repair with PEG within various time frames and with or without autografting, to assess its effectiveness as a helpful addition to current nerve repair methods. ^{1 2 3 4 5}

Who Is on the Research Team?

Wesley Thayer, MD, PhD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with a specific type of severe nerve injury in the upper extremity, known as Sunderland Class 5. They must be candidates for immediate surgery, with injuries no older than 72 hours and ready to commit to a year-long treatment and evaluation schedule. Excluded are those with contaminated wounds, inadequate tissue coverage, diabetes, neuromuscular diseases, or undergoing treatments affecting neural growth.

Inclusion Criteria

I am a candidate for immediate surgery.

My injury was treated within the last 3 days.

I had surgery to repair a nerve within 2 days of being injured.

Exclusion Criteria

Patients currently enrolled in another investigational study

My surgery is planned to be done in stages.

I may not be able to finish the usual occupational therapy program.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Epineural repair using PEG for sensory nerve injuries in the upper extremity, with variations in timing and use of autografting

Up to 72 hours post-injury

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with primary outcome measured by MRCC

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Polyethylene glycol (PEG)

Trial Overview The study tests polyethylene glycol (PEG) assisted axonal fusion technique for repairing peripheral nerve injuries. It aims to see if this method can rapidly restore function after an injury by immediately fusing severed nerves together during surgery.

How Is the Trial Designed?

Group I: epineural repair with autografting within 48 hours, using PEG Experimental Treatment 1 Intervention

epineural repair with auto grafting within 48 hours

Group II: epineural repair >24 but <72 hours using PEG Experimental Treatment 1 Intervention

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

Group III: epineural repair <24 hours using PEG Experimental Treatment 1 Intervention

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

Group IV: standard epineural repair <24 hours Active Control 1 Intervention

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

Group V: epineural repair with autografting within 48 hours Active Control 1 Intervention

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

Group VI: standard epineural repair >24 - 72 hours Active Control 1 Intervention

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

Polyethylene glycol (PEG) is already approved in United States, European Union for the following indications:

Approved in United States as Polyethylene glycol for:

• Peripheral nerve repair

Approved in European Union as Polyethylene glycol for:

• Peripheral nerve repair

Who Is Running the Clinical Trial?

Vanderbilt University

Lead Sponsor

Trials

714

Recruited

6,143,000+

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

Polyethylene glycol (PEG) significantly improves recovery after peripheral nerve repair, with the best outcomes observed when PEG is applied within 48 hours post-injury, as shown in a study involving 24 rats.

The addition of 20Hz electrical stimulation further enhances recovery, leading to better functional scores and muscle weight compared to PEG alone, indicating that combining these treatments can optimize nerve repair outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The outcome of polyethylene glycol fusion augmented by electrical stimulation in a delayed setting of nerve repair following neurotmesis in a rat model. Acharya, N., Acharya, AM., Bhat, AK., et al.[2023]

PEG-fusion repair techniques can rapidly restore axonal continuity and signaling within minutes after nerve transections, leading to significant behavioral recovery over weeks, challenging traditional views on nerve injury recovery.

Unlike conventional methods, PEG-fusion allows for successful integration of donor nerve allografts without the need for tissue matching or immunosuppression, suggesting a new approach to treating peripheral nerve injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conundrums and confusions regarding how polyethylene glycol-fusion produces excellent behavioral recovery after peripheral nerve injuries. Bittner, GD., Sengelaub, DR., Ghergherehchi, CL.[2020]

In a study involving male Lewis rats with transected median nerves, polyethylene glycol (PEG) fusion significantly improved functional recovery compared to standard suture repair, with grip strength recovery reaching 77.2% by postoperative day 98 in the PEG group.

Both PEG and PEG combined with methylene blue (PEG+MB) led to a quicker return of nerve function, with grip strength recovery observed as early as postoperative day 3.8, while the standard repair group showed minimal recovery until day 21.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polyethylene Glycol Fusion Restores Axonal Continuity and Improves Return of Function in a Rat Median Nerve Denervation Model. Frost, C., Salous, A., Ketheeswaran, S., et al.[2023]

Using polyethylene glycol (PEG) for nerve repair in two patients with total loss of sensation showed rapid improvement in sensory function, with significant recovery observed as early as 3 days post-surgery.

PEG-mediated fusion repair prevents Wallerian degeneration and muscle atrophy, suggesting a potential shift in treatment for peripheral nerve injuries by allowing faster and more effective recovery compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid and effective fusion repair of severed digital nerves using neurorrhaphy and bioengineered solutions including polyethylene glycol: A case report. Lopez, S., Bittner, GD., Treviño, RC.[2023]

In a rat model of sciatic nerve injury, polyethylene glycol (PEG) was found to rapidly restore axonal continuity within minutes, showing significant improvements in nerve function over 12 weeks compared to traditional repair methods.

PEG treatment led to a notable increase in motor axon counts and restored behavioral functions by up to 50%, suggesting it could greatly enhance the management of traumatic peripheral nerve injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate Enhancement of Nerve Function Using a Novel Axonal Fusion Device After Neurotmesis. Riley, DC., Boyer, RB., Deister, CA., et al.[2022]

In a study involving 29 rats with sciatic nerve repairs, PEG hydrogel showed a significant reduction in scar tissue formation compared to fibrin glue, suggesting it may promote better healing conditions.

Both PEG hydrogel and fibrin glue resulted in similar muscle strength recovery after 10 weeks, indicating that PEG hydrogel is as effective as fibrin glue for nerve repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary investigation of a polyethylene glycol hydrogel "nerve glue". Isaacs, J., Klumb, I., McDaniel, C.[2021]

Polyethylene glycol (PEG) has shown significant potential in enhancing nerve regeneration after peripheral nerve injuries, as it helps restore axon continuity and inhibits Wallerian degeneration, based on a review of 16 animal studies and one human study.

Most studies reported favorable outcomes with PEG treatment, indicating its effectiveness in improving nerve function, although further research is needed to clarify optimal timing for treatment after injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polyethylene Glycol: The Future of Posttraumatic Nerve Repair? Systemic Review. Paskal, AM., Paskal, W., Pietruski, P., et al.[2023]

Polyethylene glycol (PEG) has been shown to enhance the repair of severed peripheral nerves in vertebrate models, indicating its potential as a therapeutic agent in nerve regeneration.

In a study using B35 rat neuroblastoma cells, higher concentrations of PEG (50%, 75%, and 100%) increased cell fusion but also decreased cell viability, highlighting a trade-off between effective fusion and cell health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of polyethylene glycol (PEG) fusion in cultured neuroblastoma cells via flow cytometry: Techniques & optimization. Hoffman, AN., Bamba, R., Pollins, AC., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6471459/

Polyethylene Glycol: The Future of Posttraumatic Nerve ... PEG therapy is a promising prospect that may improve the surgical treatment of peripheral nerve injuries in the clinical practice.

2. jneurology.com jneurology.com/articles/polyethylene-glycol-treatment-for-peripheral-nerve-repair-in-preclinical-models.html

Polyethylene Glycol Treatment for Peripheral Nerve Repair ... The advantages of using PEG as a treatment for peripheral nerve injury were compared to controls, and then the amount of significant findings in ...

3. mdpi.com mdpi.com/1648-9144/61/4/624

Harnessing Polyethylene Glycol 3350 for Enhanced ... The findings of this study indicate that PEG admission in cases of sciatic nerve damage significantly enhances and accelerates nerve regeneration. Subsequent ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04789044

Evaluating the Safety and Efficacy of Polyethylene Glycol ... The overall objective of this study is to determine the safety of PEG fusion when used with primary repair or reconstruction in patients with an acute upper ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6475191/

Polyethylene glycol (PEG) and other bioactive solutions ... PEG-fusion produces rapid and dramatic recovery of function following rat peripheral nerve injuries. Keywords: Polyethylene glycol fusion, peripheral nerve ...