PEG Fusion for Peripheral Nerve Injury

Recruiting in Bethesda (>99 mi)

+6 other 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

Trial Summary

What is the purpose of this trial?

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 extremity peripheral nerve injury. PEG is safe and effective for extending the half-life of circulating pharmaceutical products, when used in conjunction with a topical hemostatic agent in surgical wounds, and when used as a colon cleanser for endoscopic surgical procedures. However, PEG fusion has not been rigorously tested as a safe reagent to promote nerve regeneration in humans. Therefore, the goal of this Phase 2a clinical trial is to establish safety data and to examine the effect of PEG fusion on clinical outcomes including recovery of sensory and motor function. Results will be externally validated using data collected in the DoD funded prospective NERVE study and will provide preliminary evidence to power a larger phase II efficacy trial.

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.

What data supports the effectiveness of the treatment NTX-001, Polyethylene Glycol (PEG) Mediated Fusion, for peripheral nerve injury?

Research shows that PEG fusion can rapidly restore nerve function and improve recovery in animal models with nerve injuries. In cases of nerve damage, PEG fusion has been shown to quickly reestablish nerve connections and improve sensory and motor recovery, suggesting it could be a promising treatment for peripheral nerve injuries. ^{1 2 3 4 5}

Is PEG Fusion safe for humans?

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 patients experienced side effects like swelling and scar development, which improved over time. Overall, the safety data is limited but suggests potential for safe use with careful monitoring. ^{1 2 3 5 6}

How is the PEG Fusion treatment different from other treatments for peripheral nerve injury?

PEG Fusion is unique because it rapidly restores axonal continuity and improves sensory and motor recovery by fusing severed nerve ends, unlike traditional methods that rely on slow axonal regrowth. This approach prevents muscle atrophy and Wallerian degeneration, leading to faster and more effective recovery. ^{1 2 3 4 5}

Research Team

Jaimie Shores, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. Scotland pubmed.ncbi.nlm.nih.gov

Analysis of polyethylene glycol (PEG) fusion in cultured neuroblastoma cells via flow cytometry: Techniques & optimization. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Polyethylene Glycol Fusion Restores Axonal Continuity and Improves Return of Function in a Rat Median Nerve Denervation Model. [2023]

3. Switzerland 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Polyethylene glycol rapidly restores axonal integrity and improves the rate of motor behavior recovery after sciatic nerve crush injury. [2018]

5. United States 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. [2019]

6. India pubmed.ncbi.nlm.nih.gov

Conundrums and confusions regarding how polyethylene glycol-fusion produces excellent behavioral recovery after peripheral nerve injuries. [2020]