Regenerative Endoscopy in Refractory Perianal Crohn's Disease

Official title

Autologous Mechanical tSVF Injection in Refractory Perianal Fistulizing Crohn's Disease: A Single Arm Pilot Feasibility Study

Overview

Perianal fistulizing Crohn's disease (pCD) represents a severe phenotype of Crohn's disease, affecting approximately 20-30% of patients and resulting in chronic drainage, recurrent sepsis, impaired continence, and reduced quality of life. Despite optimization of biologics, antibiotics, and surgical drainage, durable healing remains difficult to achieve. Conventional surgical approaches such as curettage or seton management alone yield modest remission rates, and repeated procedures may compromise sphincter integrity. Autologous mechanically processed tissue stromal vascular fraction (tSVF) is derived from adipose tissue using non enzymatic methods and can be prepared and reinjected during the same operative session. Unlike culture-expanded or enzymatically isolated cell products, mechanical tSVF retains a native adipose micro architecture containing stromal cells, perivascular elements, endothelial progenitors, extracellular matrix components, and bioactive cytokines. This heterogeneous microenvironment is hypothesized to exert immunomodulatory, pro angiogenic, and regenerative effects that may enhance tract healing while preserving sphincter function. Mechanical processing avoids enzymatic digestion, cell expansion, and complex laboratory infrastructure, making it potentially more feasible and cost effective in real world settings. However, high quality prospective data evaluating mechanically processed autologous tSVF specifically in refractory complex pCD remain limited, and feasibility data are required before undertaking a large randomized trial. This single arm pilot feasibility study is therefore designed to evaluate procedural feasibility, safety, and preliminary signals of clinical and radiological healing following mechanical tSVF injection in refractory complex perianal Crohn's disease. The results will inform design parameters, outcome variability, and sample size estimation for a future definitive multicenter trial.

Detailed description

All participants receive a single session of autologous mechanical tSVF injection following the standardized standard operating procedure.

1. Removal of existing setons where applicable (documented in CRF 3) 2. Tumescent liposuction: harvest of 60-120 mL adipose tissue from lower abdomen or flank under tumescent anaesthesia (Klein formula) 3. Mechanical emulsification and filtration to obtain tSVF using the specified device and Standard operating procedure - minimum acceptable yield ≥5 mL 4. Intraoperative tSVF product quality check: Gram stain from final product; viability assessment by Trypan Blue exclusion where feasible; flow cytometry sample aliquot (sub-study, see Appendix D) 5. Fistula preparation: examination under anaesthesia (EUA), curettage of tract, and identification/closure of internal opening 6. tSVF injection (6-12 mL total): circumferentially around internal opening region in 0.1-0.3 mL blebs; along tract length avoiding sphincter penetration 7. Standard postoperative wound care and antibiotics per unit protocol

Interventions

• Procedure Autologous Mechanical Tissue Stromal Vascular Fraction (tSVF) Injection
  Autologous adipose tissue harvest by tumescent liposuction followed by same-session mechanical processing to obtain tissue stromal vascular fraction (tSVF) and local injection into the perianal fistula tract and internal opening region

Primary outcome measures

• Feasibility and Preliminary Efficacy at Week 24 [Time frame: Week 24]

Secondary outcome measures (1)

• Cessation of fistula drainage [Time frame: Week 24 & 52]

Eligibility criteria

Inclusion criteria

• Age 18-65 years
• Crohn's disease with complex perianal fistula (≥1 secondary tract or internal opening involvement)
• Refractory to ≥1 biologic and/or ≥1 prior sphincter sparing procedure
• No abscess on screening MRI
• Mild or no proctitis on endoscopic assessment
• CDAI <220
• Stable IBD therapy ≥8 weeks
• Able to provide informed consent

Exclusion criteria

• Rectovaginal fistula
• Severe active proctitis requiring urgent escalation
• Malignancy in tract or pelvic region
• Pregnancy or lactation
• ASA IV status or bleeding disorder
• MRI contraindications

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

India · 2 centers

• AIG Hospitals — Hyderabad
• AIG Hospitals — Hyderabad

Identifiers

NCT: NCT07652632 · tSVF 1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗