Axoguard Nerve Cap for Amputation Recovery

(REPOSE-XL℠ Trial)

Recruiting at 1 trial location

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Axogen Corporation

Must not be taking: Chemotherapy, Radiation, Immunosuppressants, others

Disqualifiers: Infection, Diabetes, Neuropathy, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This pilot study evaluates the tolerability and feasibility of the Axoguard Large-Diameter Nerve Cap (sizes 5-7 mm) for protecting and preserving terminated nerve endings after limb trauma or amputation when immediate attention to the nerve injuries is not possible.

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, or if you are immunosuppressed, you would not be eligible to participate.

What data supports the effectiveness of the treatment Axoguard Nerve Cap for amputation recovery?

The Axoguard nerve wrap, a component of the Axoguard Nerve Cap, has shown promising results in treating compression neuropathies, with no safety concerns reported. Additionally, in a case of lingual nerve injury, the use of an Axoguard nerve conduit led to improved sensation and taste, indicating its potential effectiveness in nerve repair. ^{1 2 3 4 5}

Is Axoguard Nerve Cap generally safe for human use?

Previous studies on Axoguard nerve wrap, which is similar to Axoguard Nerve Cap, have shown no safety concerns, with no reported cases of infection, persistent inflammation, or recurrent issues. However, there was a case of necrotic granulomatous inflammation (a type of tissue reaction) reported after its use, indicating that while generally safe, there may be rare adverse reactions. ^{1 5 6 7 8}

How is the Axoguard Nerve Cap treatment different from other treatments for amputation recovery?

The Axoguard Nerve Cap is unique because it uses a bioabsorbable material made from porcine small intestine submucosa to cap nerve endings, which helps prevent painful neuroma formation after amputation. This approach provides a physical barrier to protect nerves and creates a favorable environment for nerve healing, unlike traditional methods that may not address neuroma prevention as effectively. ^{1 2 3 6 7}

Eligibility Criteria

This trial is for adults aged 18-80 who have had limb trauma or amputation and are scheduled for nerve surgery within 6-12 months, or need surgery to address nerve ends. Participants must have a terminated nerve end between 4-7 mm in diameter and be able to cover it with the Axoguard Nerve Cap. They should not be undergoing treatments affecting neural growth, have uncontrolled diabetes, infections, allergies to anesthetics, sensitivity to porcine products, or other conditions that would exclude them.

Inclusion Criteria

I have had an amputation and am having surgery to treat my nerve ends.

I am between 18 and 80 years old.

I am willing and able to follow the study's treatment and check-up schedule.

Exclusion Criteria

I am immunosuppressed or will be receiving immunosuppressive therapy.

I have diabetes with an HbA1c of 8% or higher, or diabetic neuropathy near my amputation site.

I experience numbness or pain in my hands/feet from past chemotherapy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Surgery and Implantation

Implantation of the Axoguard Nerve Cap® at the time of surgery

1 day

1 visit (in-person)

Post-operative Monitoring

Monitoring of adverse events and pain-related measures post-surgery

15 months

Regular visits at 2 weeks, 1, 3, 6, 9, 12, and 15 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Axoguard Nerve Cap® (Nerve Protection Device)

Trial Overview The study tests the Axoguard Large-Diameter Nerve Cap (sizes 5-7 mm) on patients with limb trauma or amputations. It aims to protect and preserve terminated nerve endings when immediate repair isn't possible. The feasibility and tolerability of this device will be evaluated over time.

Participant Groups

Group I: Axoguard Nerve Cap® Experimental Treatment 1 Intervention

Active Comparator: Porcine derived extracellular matrix (ECM) based Nerve Termination Device Implantation of appropriate diameter of Axoguard Nerve Cap® (sizes 5-7 mm) at the time of surgery

Who Is Running the Clinical Trial?

Axogen Corporation

Lead Sponsor

Trials

11

Recruited

5,600+

Findings from Research

AxoGuard nerve wrap, used in conjunction with neurolysis and tenosynovectomy, has previously shown no safety concerns in treating recurrent carpal and ulnar tunnel syndrome, but a case of necrotic granulomatous inflammation was reported 2.5 months after its application.

As a salvage treatment, a NuShield placental allograft was successfully used around the median nerve, indicating that placental allografts may be effective for patients with compression neuropathy who do not respond to other surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Necrotic Granulomatous Inflammation after Use of Small Intestine Submucosa Matrix for Recurrent Compression Neuropathy. Koenig, ZA., Burns, JC., Hayes, JD.[2022]

A novel technique using Tisseel fibrin glue to stabilize an Axoguard nerve conduit during lingual nerve injury repair resulted in successful recovery with fewer sutures needed.

Five months after the surgery, the patient reported improved sensation and taste, and neurosensory examination confirmed functional recovery, indicating the technique's efficacy in nerve repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Fibrin Glue as an Adjunct in the Repair of Lingual Nerve Injury: Case Report. Theberge, NP., Ziccardi, VB.[2017]

In a study involving 91 rats, using a closed-end bioabsorbable nerve conduit significantly reduced neuropathic pain compared to no capping, indicating its efficacy in preventing painful amputation neuromas.

Both open and closed-end conduits prevented the formation of neuromas and reduced neuroinflammation, but the closed-end version was more effective in blocking scar formation and protecting the nerve stump.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nerve capping treatment using a bioabsorbable nerve conduit with open or closed end for rat sciatic neuroma. Hama, S., Uemura, T., Onode, E., et al.[2022]

In a retrospective study of seven patients, interdigital neurorrhaphy after neuroma resection showed significant improvements in pain and upper limb functionality, with mean improvements of 29.8% on the Visual Analog Scale (VAS) and 55.5% on the Disabilities of the Arm, Shoulder and Hand (DASH) score over an average follow-up of 28.3 months.

No long-term complications were reported, suggesting that interdigital neurorrhaphy is a safe and feasible surgical option for treating painful digital neuroma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interdigital direct neurorrhaphy for treatment of painful neuroma due to finger amputation. Martins, RS., Siqueira, MG., Heise, CO., et al.[2022]

In a study comparing two types of nerve conduits (NeuraGen and AxoGuard) used in lingual nerve microsurgery, both conduits resulted in similar improvements in sensory recovery, indicating their comparable efficacy.

All patients achieved functional sensory recovery (FSR) as per the Medical Research Council Scale, with no significant differences in outcomes between the two conduits, suggesting both are effective options for nerve repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lingual Nerve Microsurgery Outcomes Using 2 Different Conduits: A Retrospective Cohort Study. Wilson, MT., Chuang, SK., Ziccardi, VB.[2017]

In a study involving 18 male Lewis rats, the Axoguard Nerve Connector (SIS) promoted a favorable macrophage type 2 (M2) response, which is associated with tissue healing and regeneration, compared to the NeuraGen Nerve Guide (Col) that showed a dominant macrophage type 1 (M1) response linked to inflammation.

The SIS conduits demonstrated better vascularization and fibroblast ingrowth, while the Col conduits formed a capsule-like structure, indicating that the choice of biomaterial significantly influences the host tissue response and could affect clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparative Study of Porcine Small Intestine Submucosa and Cross-Linked Bovine Type I Collagen as a Nerve Conduit. Zhukauskas, R., Fischer, DN., Deister, C., et al.[2022]

The study evaluated a new biocompatible nerve conduit made from PRGD/PDLLA, which significantly reduced neuropathic pain and improved recovery in rats after sciatic nerve amputation, as indicated by lower autotomy scores and better tissue structure.

The PRGD/PDLLA conduits not only prevented inflammatory infiltration and excessive collagen deposition but also promoted proper myelination and nerve repair, suggesting they could be an effective solution to prevent neuroma formation in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Painful Terminal Neuroma Prevention by Capping PRGD/PDLLA Conduit in Rat Sciatic Nerves. Yi, J., Jiang, N., Li, B., et al.[2023]

In a study involving 10 rabbits, silicone capping of amputated nerves effectively prevented neuroma formation when the cap's length-to-diameter ratio was maintained between 5:1 and 10:1, indicating a specific design is crucial for success.

In a clinical trial with 18 patients suffering from traumatic neuromas, 15 patients experienced relief from pain after silicone capping, although some required revision surgery, highlighting the treatment's potential effectiveness but also the need for careful monitoring and follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The prevention and treatment of amputation neuromata by silicone capping. Swanson, AB., Boeve, NR., Lumsden, RM.[2022]

References

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

Necrotic Granulomatous Inflammation after Use of Small Intestine Submucosa Matrix for Recurrent Compression Neuropathy. [2022]

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

Use of Fibrin Glue as an Adjunct in the Repair of Lingual Nerve Injury: Case Report. [2017]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Nerve capping treatment using a bioabsorbable nerve conduit with open or closed end for rat sciatic neuroma. [2022]

4. Austria pubmed.ncbi.nlm.nih.gov

Interdigital direct neurorrhaphy for treatment of painful neuroma due to finger amputation. [2022]

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

Lingual Nerve Microsurgery Outcomes Using 2 Different Conduits: A Retrospective Cohort Study. [2017]

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

A Comparative Study of Porcine Small Intestine Submucosa and Cross-Linked Bovine Type I Collagen as a Nerve Conduit. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Painful Terminal Neuroma Prevention by Capping PRGD/PDLLA Conduit in Rat Sciatic Nerves. [2023]

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

The prevention and treatment of amputation neuromata by silicone capping. [2022]