Tissue Therapy of Transsphincteric Anal Fistula (REP-PAF)

Repairing Peri-Anal Fistulas With Regenerative Cell Therapeutics

This clinical study aims to evaluate the outcome of the treatment of complex perianal fistulas (PAF) by the combination of minimal surgical debridement with regenerative cellular therapeutics.

Study Overview

• Status: Recruiting
• Conditions: Anal Fistula
• Intervention / Treatment: Drug: ADRC injection; Drug: ADRC001 injection

Detailed Description

After being informed about the study and potential risks, all patients giving written informed consent will undergo screening serology and preoperative work-up to determine eligibility for study entery. Patients who meet the eligibility requirements will be treated for their fistulas by combined minor surgical debridement of the fistula tract and closure of the internal orifice as well as liposuction from the abdominal wall. Regenerative cells- enriched lipoaspirate will be injected around the entire length of the fistula tract. The first five patients will receive their own regenerative cells and act as donors for the next included patients, but they will not be included in the final analysis. The rest of the included patients (70) will be randomized in double-blinded manner (participant and investigator) in a 1:1 ratio to either recieve own regenerative cells (ADRC Adipose-Derived Regeneative Cells) or donated cultured regenerative cells (ADRC001). All included patients will be scheduled for follow-up at 3, 6 and 12 months after treatment.

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Karam M Sørensen, Ph.D; Phone Number: +4565415190; Email: ouh.a.forskningsenheden@rsyd.dk
• Study Contact Backup: Name: Tina D Hansen; Phone Number: +4565415190; Email: ouh.a.forskningsenheden@rsyd.dk

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Recruiting
    • Odense University Hospital
    • Contact: Karam M Sørensen, Ph.D; Phone Number: +4565415190; Email: ouh.a.forskningsenheden@rsyd.dk
    • Contact: Tina D Hansen; Phone Number: +4565415190; Email: ouh.a.forskningsenheden@rsyd.dk
    • Principal Investigator: Karam M Sørensen, Phd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criterion:

Adult patients (>= 18years) with complex anal fistula (high transsphincteric or suprasphincteric), with involvement of more 30% of the anal sphincter referred to the surgical department at Odense University Hospital for treatment, and who are:

• able to communicate with Danish language
• able to provide informed consent
• having address in the region of southern Denmark during the study

Exclusion criteria:

1. Signs of suppuration/cavitation around the fistula
2. Simple or low anal fistula, which can be treated by simple surgical incision
3. Ano-vaginal and recto-vaginal fistula
4. The presence of more than one fistula tract, more than two external orifices or more than one internal orifice
5. Inflammatory Bowel Disease
6. Immunosuppression (due to clinical condition or medical therapy)
7. Malignancy within 5 years
8. Previous radiotherapy of the abdomen and pelvis
9. BMI under 18.5
10. Allergy against the antibiotics: Penicillin and streptomycin.
11. Coagulopathy
12. Pregnancy and lactation (positive HCG (human chorionic gonadotropin) test)
13. Verified syphilis, HIV, or hepatitis on screening test

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous ADRC; Allocated patients will be treated for the fistula by combined surgical debridement of the fistula tract, closure of the internal orifice and injection of 30 ml lipoaspirate around the entire length of the fistula tract. Lipoaspirate will be harvested from the anterior abdominal wall under the same operation. Two hours later, the patient will receive injection of 5 ml suspension including 30 million autologous adipose-derived regenerative cells ADRC and injected at the same site of the lipoaspirate injection.	Drug: ADRC injection; Allocated patients will receive injection of 5 ml suspension including 30 million autologous adipose-derived regenerative cells ADRC and injected at the same site of the lipoaspirate injection.; Other Names: Liposuction; Surgical debridement of fistula tract and closure of internal orifice; Injection of lipoaspirate
Experimental: allogenic ADRC001; Allocated patients will be treated for the fistula by combined surgical debridement of the fistula tract, closure of the internal orifice and injection of 30 ml lipoaspirate around the entire length of the fistula tract. Lipoaspirate will be harvested from the anterior abdominal wall under the same operation. Two hours later, the patient will receive injection of 5 ml suspension including 30 million cultured allogenic adipose-derived regenerative cells ADRC001 and injected at the same site of the lipoaspirate injection.	Drug: ADRC001 injection; Allocated patients will receive injection of 5 ml suspension including 30 million allogenic adipose-derived regenerative cells ADRC001 and injected at the same site of the lipoaspirate injection.; Other Names: Liposuction; Surgical debridement of fistula tract and closure of internal orifice; Injection of lipoaspirate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Healing rate (percentage)	Clinical healing is defined as closure of the external opening(s), absence/cessation of discharge and swelling by palpation.	at 6 and 12 months follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QoL	functional outcome regarding quality of life, measured by Short Form SF-36 Rand questionnaire.	at12 months follow-up.
Fecal Incontinence	functional outcome regarding fecal incontinence, measured by Wexner Fecal Incontinence score.	at12 months follow-up.
Risk factors for recurrence of fistula.	Risk factors for recurrence of fistula including demography, prevoius surgery for fistula, disease duration and treatment arm.	at12 months follow-up.
Radiological healing.	Radiological healing, defined as no visible fistula or fluid collection more than 5 mm at MR imaging.	at12 months follow-up.
Treatment efficacy.	comparison of the healing rate of the fistula between patients receiving ADRC and patients receiving ADRC001 (autologous vs. allogenic cells)	at12 months follow-up.
Cellular composition	Definition of the cellular compisition of the ADRC and ADRC001 regarding cellular surface markers (CD14, CD31, CD34, CD45, CD73, CD90, CD105, CD235a, HLA-ABC og HLA-DR) using flowcytometry.	at 3 months follow-up.
Transplantation-related alloantibodies	Registration of the number of patients developing serum alloantibodies specific to donor genotypes, by assessment of anti-HLA (class I and II).	at12 months follow-up.

Collaborators and Investigators

• Sponsor: University of Southern Denmark
• Investigators: Principal Investigator: Karam M Sørensen, OUH

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2024
• Primary Completion (Estimated): October 8, 2027
• Study Completion (Estimated): October 8, 2028

Study Registration Dates

• First Submitted: February 25, 2024
• First Submitted That Met QC Criteria: March 4, 2024
• First Posted (Actual): March 12, 2024

Study Record Updates

• Last Update Posted (Estimated): November 5, 2024
• Last Update Submitted That Met QC Criteria: November 2, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: stem cells; anal fistula; ADRC
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Rectal Diseases; Digestive System Fistula; Intestinal Fistula; Fistula; Rectal Fistula
• Other Study ID Numbers: 260-2021-NQ; 2022-502659-73 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No