Perianal Fistula Treatment With Autologous Adipose Tissue Injection

Sponsor

Azienda Ospedaliero, Universitaria Pisana (Other)

Overall Status

Unknown status

CT.gov ID

NCT03913910

Collaborator

(none)

100

Enrollment

Location

16.9

Anticipated Duration (Months)

5.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Perianal Fistula	Procedure: Lipogems

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Feb 1, 2019

Anticipated Primary Completion Date :

Dec 31, 2019

Anticipated Study Completion Date :

Jun 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Lipogems Lipogems injection in the internal orifice, mucosal, submucosal and muscular layer, in the fistula tract and external orifice.	Procedure: Lipogems 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.

Arm

Intervention/Treatment

Lipogems

Lipogems injection in the internal orifice, mucosal, submucosal and muscular layer, in the fistula tract and external orifice.

Procedure: Lipogems

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.

Outcome Measures

Primary Outcome Measures

Healing [12 months]
Closing of the fistula tract (internal and external orifice)

Secondary Outcome Measures

Safety collecting all types of adverse events [12 months]
All types of adverse events intra-, peri-, or post-operative will be collected
Pain assessed using the Visual Analogue Scale (VAS) for pain [12 months]
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.
Continence [12 months]
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).
Patient's satisfaction [12 months]
Patient's satisfaction will be evaluated using a visual analogue scale 0-5, where 0 is no satisfaction and 5 is maximum satisfaction.
Non inferiority compared with the Advancement flap technique [12 months]
Non-inferiority will be determined comparing healing rate of Lipogems with retrospective data on the advancement flap.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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