Background Phenome-wide association studies (PheWAS) can reveal novel associations between variants in drug-target genes and disease and, as such, can be used to predict new drug-indication pairs for repurposing drugs with a known mechanism of action. A platelet-derived growth factor receptor beta (PDGFRβ) PheWAS demonstrated that patients with a single nucleotide variant that reduces PDGFRβ expression exhibit a higher prevalence of chronic skin ulcers, skin grafts, and reconstructive surgeries. Recombinant human platelet derived growth factor BB (rhPDGF) is a therapeutic that binds to and activates PDGFRβ and has received FDA approval for multiple indications, including improving healing of lower extremity diabetic neuropathic ulcers, augmenting periodontal bone and soft tissue reconstruction, and stimulating orthopedic bone regeneration. Leveraging a drug-repurposing methodology informed by PheWAS, we hypothesize that rhPDGF will provide therapeutic benefit in the treatment of other complex wounds, like full-thickness surgical wounds of the head or neck that cannot heal by primary intention following skin cancer excision.

Methods This prospective, double-blinded, single-site study aims to enroll 40 participants, randomized at a ratio of 1:1, comparing the efficacy of an advanced wound matrix saturated with rhPDGF or saline. Comparisons will be stratified by anatomical location (scalp/forehead versus face/neck) and maximum surgical defect dimensions (< 3cm versus > 3cm). The primary outcome of this study will evaluate the time in days to 81-100% granulation of the wound bed by expert clinical assessment of daily photographs. Secondary outcomes will assess the superiority of the rhPDGF-enhanced wound matrix relative to control with respect to wound granulation rate, epithelialization, complete wound healing, and patient reported outcomes (PROMs).

Discussion Although reconstructive techniques are available for healing complex head and neck wounds following skin cancer excision, these procedures are invasive, and older, frail patients are often suboptimal candidates. There remains a need for less invasive therapeutic approaches that reduce the healing time and mitigate the morbidity associated with chronic wounds. A PheWAS analysis identified complex wounds requiring reconstructive surgery as a novel drug-indication pair for repurposing rhPDGF. This protocol is designed to evaluate the efficacy of an rhPDGF-enhanced advanced wound matrix for healing complex head and neck wounds post skin cancer excision that cannot heal by primary intention.

Clinical trial registration This trial is registered at ClinicalTrials.gov (NCT06634030).

I have read the journal's policy and the authors of this manuscript have the following competing interests: GK, FG, DRO, JKS, and JMP do not have any competing interests to declare. CRC, BSB, RAT, MDL, BWG, BS, JS, TWM, and WPT have effort funded, in part, through a collaboration with Lynch Regenerative Medicine. SEL is the author and inventor on multiple patents related to PDGF. These patents are licensed to multiple companies. In exchange for these licenses, Dr. Lynch has received a portion of milestone payments and stock in multiple companies.

This trial is registered at ClinicalTrials.gov (NCT06634030).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by the Vanderbilt Health IRB (IRB #240597). This study utilized written consent forms.

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No datasets were generated or analysed during the current study. All relevant data from this study will be made available upon study completion.