Adipose Tissue Injection for the Treatment of Complex Cryptoglandular Perianal Fistula (AdiTiF)

The incidence of complex cryptoglandular anal fistula is high, it affects eminently young patients and implies an important alteration in their quality of life and high prevalence in sick leave. Its treatment remains a real challenge due to the limited efficacy of sphincter preservation techniques and the inevitable risk of faecal incontinence in those cases that require surgery. Goals: To evaluate the efficacy and safety of the injection of freshly collected autologous adipose tissue as a minimally invasive, highly reproducible alternative, without risk for the continence of the patient, and of very low cost, in the treatment of complex cryptoglandular anal fistula. Methodology: Prospective multicenter, randomized, double-blinded, parallel-group, placebo-controlled clinical trial. Randomization list for each center to ensure the balance of inter-center allocation. Patients older than 18 years with cryptoglandular anal fistula with suppuration for more than 6 weeks and less than 1 year, who have received at most: curettage and drainage placement will be included. Treatment group: injection of fresh autologous fat into the fistulous tract, after curettage and closure of the internal orifice, and after lipoaspirate fat in the abdomen and centrifugation thereof. Placebo group: curettage and closure of the internal orifice and simulated intervention in the abdomen. Evaluation: protocolized clinical history and fistula complexity score (CFS), subjective perception of its pathology, St.Marks continence score, Quality of life questionnaire (QoLAF), and endoanal 3D ultrasound, at baseline, at one week, and at 3, 6 and 12 months after the intervention. The patients and the evaluator will be blind to the treatment. Patients who cannot end up receiving treatment due to intraoperative incidents or medical decision will be excluded from the study (post randomization exclusion). In each center there will be a blind evaluator to perform the follow-ups and endoanal ultrasound.

Study Overview

• Status: Recruiting
• Conditions: Anal Fistula
• Intervention / Treatment: Procedure: sham; Procedure: Injection of autologous freshly collected adipose tissue

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Terrassa, Barcelona, Spain, 08221
      • Recruiting
      • Hospital Universitari Mutua Terrassa
      • Contact: Pilar Arcusa; Phone Number: 937365050; Email: parcusa@mutuaterrassa.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients over 18 years
• Anal fistula with suppuration for more than 6 weeks and less than 1 year, that have not received any previous treatment or at most: curettage and drainage placement
• Complex cryptoglandular anal fistula: medium or high transsphincteric fistula, suprasphincteric fistula and extra sphincter fistula, shown by endoanal ultrasound.
• Low transsphincteric fistulas in patients with fecal incotinence.
• Any cryptoglandular anal fistula with risk factors for anal incontinence: anterior location fistula in women, history of pelvic surgery (hysterectomy, rectal resection), history of pelvic radiotherapy or previous anal surgery
• Draining with Seton placed >2 weeks before surgery and present at the time of treatment
• Disposition and ability to comply with the study protocol
• Signed informed consent

Exclusion Criteria:

• Patients diagnosed with inflammatory bowel disease
• Previous history of perianal fistula treated with any surgery different than curettage and seton placement (this include any type of surgery with curative intention, i.e. flap, lift technique, Radiofrequency, laser, stem cells, Filac, etc)
• Presence of Rectovaginal fistula
• Technical impossibility for lipoaspirate (liposuction) technique.
• Presence of perianal collections larger than 2cm
• Presence of several paths from 1 internal hole only
• Presence of secondary fistula paths or tracts
• Perianal surgery necessary at the time of planning the fistula treatment, for reasons other than fistula.
• Major surgery needed within 28 days of recruitment
• Immunomodulator treatment or corticotherapy in a previous period of 6 months
• Stoma patients
• Serious medical or psychiatric illness that requires frequent hospitalization.
• Pregnancy, pregnancy plans or breastfeeding in the next 12 months
• Active smokers, or ex-smokers of less than 3 months

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group	Procedure: Injection of autologous freshly collected adipose tissue; injection of fresh autologous fat, previously lipoaspirates from the patient's abdomen and centrifugated, into the fistulous tract, after curettage and closure of the internal opening.
Sham Comparator: Control group	Procedure: sham; curettage and closure of the internal orifice of the anal fistula and simulated intervention in the abdomen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete fistula healing	Comparison of the proportion of cases with complete fistula healing within 24 weeks of the intervention, defined as the absence of drainage through the external orifice, its complete reepithelialization and the absence of collections confirmed by endoanal ultrasound.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient's Quality of life	Improvement in quality of life (measured with the Quality of Life in Patients with Anal Fistula Questionnaire, QoLAF). Score from 14 to 70, where 14 means "no quality of life alteration" and 70 means "severe quality of life alteration".	6 and 12 months after treatment.
Patient's Subjective Perception	Improvement in patient subjective evaluation using a Visual Analogue Scale (VAS). Score from 0 to 10, where 0 means "no problem" and 10 means "severe problem and alteration of my quality of life".	6 and 12 months after treatment.
Fistula severity	Improvement in fistula severity according to the Complexity Fistula score (CFS). Score from 3 to 15, where 3 means "low complexity" and 15 means "high complexity"	6 and 12 months after treatment.
Adverse events	Evaluation of the safety by the incidence of adverse events and serious adverse events.	3, 6 and 12 months after treatment.

Collaborators and Investigators

• Sponsor: Hospital Mutua de Terrassa

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2020
• Primary Completion (Anticipated): November 14, 2023
• Study Completion (Anticipated): October 1, 2024

Study Registration Dates

• First Submitted: February 7, 2021
• First Submitted That Met QC Criteria: March 7, 2021
• First Posted (Actual): March 10, 2021

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: March 1, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Pathological Conditions, Anatomical; Rectal Diseases; Intestinal Fistula; Digestive System Fistula; Fistula; Rectal Fistula
• Other Study ID Numbers: P19/035

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