Perianal Fistula Treatment With Autologous Adipose Tissue Injection

Study Overview
=================
Brief Summary
-----------------
The study aims to evaluate the efficacy of the local injection of autologous micro-fragmented adipose tissue obtained with the Lipogems®system in patients with trans-sphincteric fistulas untreatable with fistulotomy.

Detailed Description
-----------------
STUDY BACKGROUND Perianal fistulas are diseases that, by their nature, do not tend to heal spontaneously and are very rarely cured with medical treatment. Their healing is usually pursued through surgery, which often needs to be repeated due to the natural tendency of the fistulas to recur. A surgical treatment that is currently able to provide a high chance of healing is fistulotomy which, however, can injure the anal sphincter and may result in degrading scars and possible fecal incontinence. One possible strategy could be the lipofilling, i.e., autologous adipose tissue transplant containing, among the many, pericytes and progenitor cells, including adult mesenchymal stem cells. STUDY DESIGN This is a no profit interventional prospective multicenter study without drugs where 100 patients (10 each participant centre) with a diagnosis of trans-sphincteric anal fistula that is not suitable to be laid open will be enrolled. After the enrolment, medical history and clinical data will be collected and pre-operatory exams will be performed. METHODS - Harvesting of the adipose tissue The lower/lateral abdomen or, eventually, the inner/outer thigh will be chosen as donor site for adipose tissue harvesting under general or spinal anaesthesia. Before the harvesting, the donor site will be injected with 100 cc of Klein Solution (500 cc saline, 1 cc epinephrine 1/1000 IU, and 40 cc lidocaine 2%) using a disposable 17 gauge blunt cannula connected to a 60-cc luer-lock syringe. The fat will be then harvested (50-100 cc) using a 13 gauge blunt cannula connected to a 20-ml VacLok® syringe. - Processing of the adipose tissue with the Lipogems® device The harvested fat will be immediately processed in the Lipogems® processing kit (Lipogems International Spa, Milan, Italy). Lipogems® is a disposable device that mechanically reduces the size of the adipose tissue clusters while eliminating oily substances and blood residues with pro-inflammatory properties. The entire process is carried out in one surgical step in complete immersion in physiological solution minimizing any traumatic action on the cells and microarchitecture. The processed micro-fragmented fat will be collected in a 60-cc syringe and positioned to decant the excess of saline solution. At the end, the product will be transferred in several 5-cc syringes to be re-injected in the patient. - Surgical procedure and micro-fragmented adipose tissue (Lipogems®) injection The micro-fragmented autologous adipose tissue will be injected with wheals of no more than 1cc in the internal orifice, mucosal, submucosal and muscular layer, then in the fistula tract and external orifice. - Follow-up visits and outcome measures All patients will be assessed at 7 days, 1, 3, 6 and 12 months after the procedure.

Official Title
-----------------
Treatment of Perianal Fistulas Through Injection of Autologous and Micro-fragmented Adipose Tissue: a Prospective Multicentre Study

Conditions
-----------------
Perianal Fistula

Intervention / Treatment
-----------------
* Procedure: Lipogems


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients of both sexes, aged over 18 and under 80 years old. Diagnosis, confirmed by standard methods (magnetic resonance and/or trans anal ultrasound), of complex fistula (trans-sphincteric unsuitable for treatment lay-open) without any secondary tracts and no active septic processes, performed 2-4 weeks after the first perianal access drainage procedure and fistulectomy, with positioning of a drainage seton. Seton placed at least 4-6 weeks previously No previous sphincter saving procedures for the anal fistula No limitations to a periodic follow-up lasting for a total of 12 months Informed consent form signed Exclusion Criteria: Patients with multiple fistulas Active septic process Patients unable to follow the pathway required by the protocol Patients with active Human Immunodeficiency Virus, Hepatitis B Virus or Hepatitis C Virus infections Patients with Irritable Bowel Syndrome Patients with rectal-vaginal fistulas Patients with a history of cancer lasting less than 5 years Patients undergoing cortisone and/or immunosuppressive and/or anticoagulant therapy Patients with a history rectal or pelvic radiotherapy Pregnant women Patients with connective tissue diseases and/or coagulation diseases and/or uncompensated diabetes mellitus Failure to sign the informed consent form

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lipogems<br>Lipogems injection in the internal orifice, mucosal, submucosal and muscular layer, in the fistula tract and external orifice. | Procedure: Lipogems<br>* Autologous micro-fragmented adipose tissue is injected in the internal orifice, mucosal, submucosal and muscular layer, then in the fistula tract and external orifice in addition to anal flap.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Healing | Closing of the fistula tract (internal and external orifice) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety collecting all types of adverse events | All types of adverse events intra-, peri-, or post-operative will be collected | 12 months | 
| Pain assessed using the Visual Analogue Scale (VAS) for pain | Pain will be assessed using the Visual Analogue Scale for pain (VAS 0-10), where 0 is no pain and 10 is the maximum pain. | 12 months | 
| Continence | Continence will be assessed with the Wexner Continence Grading Scale. The score takes into account the type and frequency of incontinence and the extent to which it alters the patient's life. This scoring system cross-tabulates frequencies and different anal incontinence presentations (Gas/Liquid/Solid/Pad use/Need for lifestyle alterations) and sums the returned score to a total of 0-20 (where 0 = perfect continence and 20 = complete incontinence). | 12 months | 
| Patient's satisfaction | Patient's satisfaction will be evaluated using a visual analogue scale 0-5, where 0 is no satisfaction and 5 is maximum satisfaction. | 12 months | 
| Non inferiority compared with the Advancement flap technique | Non-inferiority will be determined comparing healing rate of Lipogems with retrospective data on the advancement flap. | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Autologous micro-fragmented adipose tissue, Perianal fistula, Lipogems, Mesenchymal Stem Cells