Nerve Repair with Polyethylene Glycol for Gender Dysphoria

Overseen By Patrick Assi, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2 & 3

Sponsor: Vanderbilt University Medical Center

Disqualifiers: Allergy to study drug, VTE, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve sensation after phalloplasty, a surgery for transmasculine individuals. Many patients currently experience inadequate feeling, which can lead to regret and continued distress. The researchers are testing a new method using polyethylene glycol (PEG), a compound often used in medical applications, to help nerves heal better and faster, potentially enhancing sensation. People with gender dysphoria planning to undergo phalloplasty and who can follow the study's plan may be suitable candidates.

As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to benefit from potentially improved surgical outcomes.

Do I need to stop my current medications for the trial?

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 this trial's treatments are likely to be safe?

Research has shown that polyethylene glycol (PEG) 3350, the treatment under study, is generally safe for people. Studies have found that this treatment can aid in nerve healing and improve function. Importantly, these studies reported no negative side effects related to PEG.

PEG repairs nerves by joining their outer layers, allowing them to send signals again. In past cases, PEG enabled quick nerve recovery, showing early improvements in function. This suggests that PEG is safe and effective for nerve healing, especially in surgeries like phalloplasty.

Overall, using PEG to repair nerves appears to be a promising and safe method to enhance sensation after surgery. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores a novel technique for nerve repair using Polyethylene Glycol (PEG) 3350 during phalloplasty for gender dysphoria. Unlike standard nerve repair methods, which typically involve simple suturing after saline irrigation, this approach employs PEG as a sealant to enhance nerve healing. The unique mechanism involves applying PEG along with methylene blue to the nerve ends before repairing them, potentially promoting faster and more effective nerve regeneration. This method could offer improved sensory outcomes compared to traditional techniques, which is why it's generating interest in the medical community.

What evidence suggests that polyethylene-glycol assisted nerve repair is effective for improving sensation in phalloplasty?

This trial will compare the use of polyethylene glycol (PEG) with standard methods for nerve repair in phalloplasty surgeries. Research has shown that PEG can significantly aid nerve healing. In a study with 8 patients, areas treated with PEG demonstrated noticeably better sensation compared to usual methods. Patients reported improved sensation in treated areas, indicating enhanced nerve function. PEG facilitates the reconnection of cut nerve endings, allowing them to send signals more effectively. Early results are promising, suggesting that PEG could improve sensation and quality of life for those undergoing phalloplasty. ^{1 6 7 8 9}

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 adults over 18 with gender dysphoria who are undergoing phalloplasty using tissue from their forearm. They must be willing to follow treatment and study evaluations for up to 15 months post-surgery. It's not for those allergic to PEG, with high hematocrit levels, or a history of blood clots, vein inflammation, recent stroke or heart attack.

Inclusion Criteria

I am over 18 years old.

I am diagnosed with gender dysphoria and planning to undergo forearm flap surgery for phalloplasty.

I am willing to follow all treatment and study check-up plans.

Exclusion Criteria

Patients with a hematocrit of 54% or higher

Patients with a known allergy to the study drug

I have had a blood clot, stroke, or heart attack in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Immediate Postoperative Care

Participants undergo phalloplasty with nerve repair using either standard or PEG-assisted techniques

1-2 weeks

Inpatient stay for surgery and initial recovery

Follow-up

Participants are monitored for sensory recovery and quality of life improvements

15 months

Regular follow-up visits for assessments

What Are the Treatments Tested in This Trial?

Interventions

• Phalloplasty
• Polyethylene Glycol 3350
• Polyethylene-glycol Assisted Nerve Repair
• Postoperative Quality of Life

Trial Overview The trial tests if applying polyethylene glycol (PEG) during phalloplasty can improve sensation in the newly constructed neophallus. The goal is to see if PEG helps nerves heal better after surgery, potentially enhancing quality of life.

How Is the Trial Designed?

Group I: Experimental Experimental Treatment 1 Intervention

For the experimental group, after obtaining hemostasis, prior to neurorrhaphy, the operative field will be irrigated with calcium-free Plasmalyte A® (Baxter: Deerfield, IL) throughout the neurorrhaphy. At this point, the nerves will be repaired using standard suture neurorrhaphy techniques. Subsequently, approximately 1 or 2 drops of 5mg/ml (0.5%) methylene blue in sterile water solution are applied to the trimmed nerve endings. Then, approximately 2 ccs of a 190 mM solution of 50% PEG 3.35 kD in sterile water will be irrigated onto the neurorrhaphy site and the surgeon will wait one minute prior to continuing. Following this, the repaired nerve will be irrigated with calcium-containing Lactated Ringers (Hospira; Lake Forest, IL).

Group II: Control (No Intervention) Active Control 1 Intervention

For the control groups, epineural repair will be undertaken in the standard end-to-end fashion using interrupted nylon suture after irrigation of the wound with normal saline as deemed necessary by the operating surgeon.

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05897086

Polyethylene-glycol Assisted Nerve Repair in Phalloplasty These data include demographics, such as age, sex/gender, race and ethnicity, and study-specific measures (for example, systolic blood pressure, prior ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12076360/

6. Efficacy of Polyethylene-glycol (PEG) on Nerve ... RESULTS: A total of 32 penile shaft quadrants across 8 patients were analyzed. PEG-treated patients showed significantly improved sensory scores in quadrants 2 ...

3. researchgate.net researchgate.net/publication/391817447_6_Efficacy_of_Polyethylene-glycol_PEG_on_Nerve_Recovery_Following_Phalloplasty_A_Double-blind_Randomized_Clinical_Trial

(PDF) 6. Efficacy of Polyethylene-glycol (PEG) on Nerve ... ... PEG-assisted nerve coaptation improves sensory. outcomes following phalloplasty compared to standard. neurorrhaphy. METHODS: Patients undergoing radial ...

4. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT05897086?keyword=%22Dysphoria%22

Polyethylene-glycol Assisted Nerve Repair in Phalloplasty However, this technique fails to provide adequate sensation, causing regret and persistent dysphoria. Peripheral nerve regeneration is the greatest barrier to ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39381383/

Polyethylene Glycol Fusion and Nerve Repair Success Early human clinical trials have shown promising results, although more data are needed to provide specific indications and protocols. This ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12028508/

Harnessing Polyethylene Glycol 3350 for Enhanced ... PEG 3350 enhances nerve regeneration by improving electrophysiological function, promoting axonal repair, and increasing neurotrophic factor expression.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40282915/

Harnessing Polyethylene Glycol 3350 for Enhanced ... PEG 3350 enhances nerve regeneration by improving electrophysiological function, promoting axonal repair, and increasing neurotrophic factor expression.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02359825

NCT02359825 | Nerve Repair Using Hydrophilic Polymers ... 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= ...

9. thieme-connect.com thieme-connect.com/products/ejournals/pdf/10.1055/s-0045-1811658.pdf

Polyethylene Glycol (PEG)-Assisted Axonal Fusion in the ... PEG-fusion dramatically improves structural and functional outcomes following nerve injury. Bittner and colleagues pioneered a protocol ...