PEG Fusion for Peripheral Nerve Injury

Recruiting at 6 trial locations

Overseen By Elizabeth Wysocki, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Major Extremity Trauma Research Consortium

Disqualifiers: Brachial plexus injury, Psychiatric disorder, Allergy to PEG, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 1 day

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called PEG fusion to determine its safety and effectiveness in aiding recovery from serious nerve injuries in the arms. PEG fusion, also known as NTX-001, will be applied during surgery to repair nerves that influence movement and sensation. Participants will either receive the new PEG fusion treatment or undergo conventional nerve repair. The trial seeks individuals who have recently experienced a complete nerve injury in the upper arm area due to trauma, affecting both movement and sensation. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in nerve injury recovery.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that PEG fusion is likely to be safe for humans?

Studies have shown that PEG fusion is generally safe in various medical situations. PEG often extends the duration of medicines in the body, aids during surgeries, and serves as a colon cleanser for certain procedures. However, researchers are still studying the safety of PEG fusion for nerve repair in humans, and it hasn't been thoroughly tested for aiding nerve regrowth.

Some research suggests that PEG fusion might aid early recovery of sensation and improve well-being after nerve repair, indicating potential safety. However, more information is needed to confirm this. As this trial is in an early stage, researchers continue to collect safety data. If PEG fusion proves safe for nerve repair, further studies will explore its effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for peripheral nerve injury?

Unlike the standard of care for peripheral nerve injuries, which typically involves surgical suturing, the NTX-001 treatment utilizes PEG Fusion, a novel method that enhances nerve repair. This treatment is unique because it involves the application of NTX-001 topically via an isolation chamber medical device, promoting the fusion of nerve membranes at the injury site. Researchers are excited about this treatment because it could potentially improve nerve healing efficiency and outcomes, possibly shortening recovery time compared to traditional methods.

What evidence suggests that PEG fusion might be an effective treatment for peripheral nerve injury?

Research has shown that PEG fusion, a treatment under study in this trial, might help repair damaged nerves. In earlier studies, PEG demonstrated promise by reconnecting nerve cells, crucial for healing after an injury. Animal studies and early human reports revealed that PEG fusion can successfully restore nerve function. This method might work by preventing Wallerian degeneration, a process where nerve cells break down after an injury. Although more research is needed in humans, these early findings offer hope for people with peripheral nerve injuries. ^{1 2 4 6 7}

Who Is on the Research Team?

Jaimie Shores, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with acute upper extremity peripheral nerve injuries, specifically to the axillary, radial, median, ulnar, or musculocutaneous nerves. Candidates must present within 48 hours of injury and have both sensory and motor function impairment. Exclusions include brachial plexus injuries, purely sensory nerve damage beyond the wrist, previous neurological disorders or trauma, severe psychiatric conditions that could affect follow-up compliance or pose a self-harm risk.

Inclusion Criteria

My condition involves a nerve that affects both feeling and movement.

My condition affects a nerve that controls both feeling and movement.

I have nerve damage in my arm between my shoulder and wrist.

Exclusion Criteria

Severe problems with maintaining follow up (e.g., patients who are prisoners or homeless at time of injury or who are intellectually challenged without adequate family support)

My injury affects a nerve in my arm that mainly controls feeling or a specific movement.

I have a health condition that prevents me from having surgery right now.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Patients receive either PEG mediated reconstruction or conventional nerve reconstruction within 24 hours of injury

1 day

1 visit (in-person)

Initial Follow-up

Participants are monitored for complications or problems within the first 30 days post-surgery

4 weeks

2 visits (in-person)

Extended Follow-up

Participants are monitored for recovery of sensory and motor function, pain, range of motion, and patient satisfaction

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• NTX-001
• PEG Fusion

Trial Overview

The study tests PEG fusion's safety in promoting nerve regeneration after an acute injury. Participants will undergo primary repair or reconstruction using PEG fusion to evaluate its effect on restoring sensory and motor functions. This Phase 2a trial aims to provide safety data and preliminary evidence for a larger efficacy trial.

How Is the Trial Designed?

Group I: PEG mediated reconstruction Experimental Treatment 1 Intervention

NTX-001 will be administered topically via isolation chamber medical device. Dose Unit: 2.5 mL NTX-001 is a single use surgical product intended for use as adjunct treatment in the repair of severed peripheral nerves in patients requiring standard suture neurorrhaphy.

Group II: Conventional nerve reconstruction Active Control 1 Intervention

Conventional nerve reconstruction

Who Is Running the Clinical Trial?

Major Extremity Trauma Research Consortium

Lead Sponsor

Trials

32

Recruited

27,400+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

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]

Polyethylene glycol (PEG) fusion can rapidly restore axonal integrity in crush-severed rat sciatic axons, leading to improved conduction of nerve signals and faster recovery of motor functions.

Behavioral recovery was significantly enhanced in PEG-treated rats, with early improvements observed within 24-48 hours using the foot fault test, while longer-term recovery was better assessed by the Sciatic Functional Index over several weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polyethylene glycol rapidly restores axonal integrity and improves the rate of motor behavior recovery after sciatic nerve crush injury. Britt, JM., Kane, JR., Spaeth, CS., et al.[2018]

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]

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]

The study demonstrates that polyethylene glycol (PEG) fusion technology can restore axonal continuity in rat sciatic nerves within minutes, significantly improving the conduction of action potentials and the diffusion of fluorescent dyes across the injury site.

PEG fusion not only prevents the degeneration of severed axons but also enhances the recovery of lost locomotor functions over days to weeks, suggesting a potential new approach for treating peripheral nerve injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of extracellular calcium and surgical techniques on restoration of axonal continuity by polyethylene glycol fusion following complete cut or crush severance of rat sciatic nerves. Ghergherehchi, CL., Bittner, GD., Hastings, RL., et al.[2019]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04789044

Study Details | NCT04789044 | Evaluating the Safety and ...

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 ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11456640/

Polyethylene Glycol Fusion and Nerve Repair Success

In peripheral nerve injuries, PEG has been shown to restore axolemmal continuity applied to a repaired nerve prior to the onset of WD. The repair protocol in ...

3.

apps.dtic.mil

apps.dtic.mil/sti/trecms/pdf/AD1168738.pdf

Polyethylene Glycol (PEG)-Mediated Fusion (PEG ... - DTIC

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 ...

4.

withpower.com

withpower.com/trial/phase-3-peripheral-nerve-injuries-9-2021-3853f?condition=&query=Topical+Agents&overallStatus=Recruiting&hasNoPlacebo=false

PEG Fusion for Peripheral Nerve Injury

PEG Fusion has been used in animal studies and early human case reports for nerve repair, showing promising results in restoring nerve function. However, some ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0974322724002886

Polyethylene Glycol Fusion of Nerve Injuries

Investigational techniques in nerve repair using polyethylene glycol (PEG) nerve fusion have been shown to bypass Wallerian degeneration.

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04572906

Safety and Efficacy of NTX-001 Compared to SOC in Acute ...

NTX-001 used during surgical repair of an upper extremity peripheral nerve injury in conjuction with standard suture neurorrhaphy. Intervention/Treatment ...

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38335500/

Polyethylene Glycol-Mediated Axonal Fusion Promotes ...

Conclusion: PEG fusion promotes early sensory recovery and improved patient well-being following peripheral nerve repair of digital nerves.