Study protocol and statistical analysis plan for a randomized controlled trial evaluating the safety and feasibility...

A drug-repurposing-specific phenome-wide association study (PheWAS) demonstrated that patients with a single nucleotide variant that decreases expression of platelet-derived growth factor receptor beta (PDGFRβ) have a higher prevalence of fistulas, suggesting that PDGFRβ signaling is important for tissue repair. Recombinant human platelet derived growth factor B (rhPDGF) is an FDA-approved protein-based therapeutic that signals through PDGFRβ to heal and regenerate cutaneous skin wounds, periodontal tissue, and orthopedic bone with a strong safety profile. We hypothesize that rhPDGF will benefit other conditions identified by PheWAS with a similar physiological mechanism as the existing indications, such as complex perianal fistulas that are ineligible for a fistulotomy.

This prospective, blinded, single-site study aims to enroll 12 participants, randomized at a ratio of 2:1, comparing implantation of rhPDGF-enhanced collagen to routine care procedures, and stratified by fistula etiology, idiopathic versus Crohn's disease (CD)-related. The primary outcome of this study will evaluate the technical performance of the rhPDGF-enhanced collagen implant for treatment of complex perianal fistulas as measured by the proportion of participants with successful implantation of the intervention without any intervention-related serious adverse events. The secondary outcomes will assess the preliminary safety and efficacy of the intervention based on all intervention-related adverse events, total fistulas healed, rate of fistula recurrence, and change in patient-reported symptoms. Complex perianal fistulas, idiopathic or CD-related, remain a major clinical challenge in need of new multimodal treatments aimed at tissue repair and regeneration. Pharmaceutical rhPDGF stimulation of PDGFRβ signaling promotes healing of skin, bone, and soft tissue. PheWAS revealed fistulas as a novel indication for repurposing rhPDGF. This protocol aims to evaluate the technical performance, preliminary safety and efficacy, and feasibility of rhPDGF-enhanced collagen for healing and remission of complex perianal fistulas.

This trial was approved by the Vanderbilt University Medical Center institutional review board (IRB#240585). Results will be submitted for publication in a peer-reviewed journal.

This trial is registered at ClinicalTrials.gov (NCT06632418).