Clinical trial NCT05897086: Polyethylene-glycol Assisted Nerve Repair in Phalloplasty
Official title: Nerve Repair Using Hydrophilic Polymers to Improve Tactile and Erogenous Neophallus Sensation
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
PHASE3
Conditions: Gender Dysphoria
Keywords: Phalloplasty
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2023-06-09
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Phalloplasty, a genitourinary surgery for transmasculine patients, reconstructs a neophallus using tissue transferred from other parts of the body to the groin. However, this technique fails to provide adequate sensation, causing regret and persistent dysphoria. Peripheral nerve regeneration is the greatest barrier to sensory recovery, given the slow rate of regrowth coupled with the negative effects of axonal degeneration. Topical application of polyethylene glycol (PEG) fuses severed axonal membranes, restoring the nerve's immediate ability to conduct electrical signals across the repair site. The investigators hypothesize that utilizing PEG in phalloplasties will significantly improve neophallus sensation and postoperative quality of life.

Detailed description: With more than 1.6 million transgender and nonbinary (TGNB) individuals in the United States, the investigators have witnessed an exponential increase in the number of gender-affirming surgeries performed in the last 2 decades. Of the affirming surgical spectrum, "bottom" genitourinary surgeries remain the most challenging. Specifically, phalloplasty is a masculinizing surgery for neophallus creation using free tissue transfer from other parts of the body and microvascular techniques for nerve and vessel reattachment. In radial forearm free flap (RFFF) phalloplasty, nerves from the forearm are harvested with the flap and sutured to nerves in the groin to provide postoperative sensation in the neophallus. Despite transmasculine patients ranking sensation as one of their top priorities, standard nerve coaptations performed in phalloplasty fail to provide consistent sensation with scarce dedicated research aimed at enhancing neophallus sensory outcomes. Without scientific advances, phalloplasty will remain far from perfect, negatively affecting patients' sexual health, causing dissatisfaction, and increasing the risk of surgical regret and persistent dysphoria.

Peripheral nerve regeneration remains the limiting factor for ideal sensory recovery due to the slow and inconsistent rates of regeneration, and the negative effects of axonal degeneration that occurs post-injury. The investigators advocate for using polyethylene glycol as a "fusogen" to achieve nerve fusion in peripheral nerve coaptations. Polyethylene glycol (PEG) is a hydrophilic compound that enhances the fusion of the lipid bilayer membrane of severed axons, restoring the nerve's immediate ability to conduct electrical signals across the repair site. The investigators have conducted extensive mammalian and preliminary human studies using our novel PEG-fusion protocol for nerve coaptations. In both ex-vivo and in-vivo studies in rats with severed sciatic nerves, PEG-assisted nerve coaptation restored morphological continuity and led to a remarkable early improvement in functional outcomes. In the first human PEG fusion of injured digital nerves performed by our team, the investigators saw rapid nerve recovery and early functional outcomes as early as one week. Based on the investigator's experience with PEG fusion, the investigators will be conducting a randomized clinical trial to test the efficacy of PEG-assisted nerve coaptation in achieving superior neophallus sensory function following phalloplasty.

Eligibility criteria: Inclusion Criteria:

* over the age of 18
* preoperative diagnosis of gender dysphoria and present for planned radial forearm free flap phalloplasty
* willing to comply with all aspects of treatment as well as the study evaluation schedule

Exclusion Criteria:

* a known allergy to the study drug
* a hematocrit of 54% or higher
* a history of venous thromboembolism (VTE), peripheral phlebitis, stroke, or myocardial infarction within the last 6 months.

Primary outcomes:
measure: Medical Research Council Classification (MRCC)
timeFrame: 15 months
Secondary outcomes:
measure: Vanderbilt Mini-PROM for Gender-Affirming Surgery(VMP-G)
timeFrame: 15 months
measure: Sexual Functioning and Sensation Questionnaire
timeFrame: 15 months
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Wesley Thayer, MD
role: PRINCIPAL_INVESTIGATOR
References: