Clinical trial NCT03913910: Perianal Fistula Treatment With Autologous Adipose Tissue Injection
Official title: Treatment of Perianal Fistulas Through Injection of Autologous and Micro-fragmented Adipose Tissue: a Prospective Multicentre Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Perianal Fistula
Keywords: Autologous micro-fragmented adipose tissue
Perianal fistula
Lipogems
Mesenchymal Stem Cells
Lead sponsor: Azienda Ospedaliero, Universitaria Pisana
Sponsor class: OTHER
First posted: 2019-04-12
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with a diagnosis of transphincteric anal fistula that is not suitable to be laid open.

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.

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

Primary outcomes:
measure: Healing
timeFrame: 12 months
Secondary outcomes:
measure: Safety collecting all types of adverse events
timeFrame: 12 months
measure: Pain assessed using the Visual Analogue Scale (VAS) for pain
timeFrame: 12 months
measure: Continence
timeFrame: 12 months
measure: Patient's satisfaction
timeFrame: 12 months
measure: Non inferiority compared with the Advancement flap technique
timeFrame: 12 months
Other outcomes:
Locations:
city: Pisa
country: Italy
facility: AOU Pisana - Cisanello
state: Toscana
Study officials:
References:
citation: Naldini G, Sturiale A, Fabiani B, Giani I, Menconi C. Micro-fragmented adipose tissue injection for the treatment of complex anal fistula: a pilot study accessing safety and feasibility. Tech Coloproctol. 2018 Feb;22(2):107-113. doi: 10.1007/s10151-018-1755-8. Epub 2018 Feb 16.
citation: Tremolada C, Colombo V, Ventura C. Adipose Tissue and Mesenchymal Stem Cells: State of the Art and Lipogems(R) Technology Development. Curr Stem Cell Rep. 2016;2(3):304-312. doi: 10.1007/s40778-016-0053-5. Epub 2016 Jul 13.
citation: Ceserani V, Ferri A, Berenzi A, Benetti A, Ciusani E, Pascucci L, Bazzucchi C, Cocce V, Bonomi A, Pessina A, Ghezzi E, Zeira O, Ceccarelli P, Versari S, Tremolada C, Alessandri G. Angiogenic and anti-inflammatory properties of micro-fragmented fat tissue and its derived mesenchymal stromal cells. Vasc Cell. 2016 Aug 18;8:3. doi: 10.1186/s13221-016-0037-3. eCollection 2016.
citation: Tremolada C, Ricordi C, Caplan AI, Ventura C. Mesenchymal Stem Cells in Lipogems, a Reverse Story: from Clinical Practice to Basic Science. Methods Mol Biol. 2016;1416:109-22. doi: 10.1007/978-1-4939-3584-0_6.
citation: Vezzani B, Shaw I, Lesme H, Yong L, Khan N, Tremolada C, Peault B. Higher Pericyte Content and Secretory Activity of Microfragmented Human Adipose Tissue Compared to Enzymatically Derived Stromal Vascular Fraction. Stem Cells Transl Med. 2018 Dec;7(12):876-886. doi: 10.1002/sctm.18-0051. Epub 2018 Sep 26.
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citation: Cestaro G, De Rosa M, Massa S, Amato B, Gentile M. Intersphincteric anal lipofilling with micro-fragmented fat tissue for the treatment of faecal incontinence: preliminary results of three patients. Wideochir Inne Tech Maloinwazyjne. 2015 Jul;10(2):337-41. doi: 10.5114/wiitm.2014.47435. Epub 2014 Dec 4.
citation: Bianchi F, Maioli M, Leonardi E, Olivi E, Pasquinelli G, Valente S, Mendez AJ, Ricordi C, Raffaini M, Tremolada C, Ventura C. A new nonenzymatic method and device to obtain a fat tissue derivative highly enriched in pericyte-like elements by mild mechanical forces from human lipoaspirates. Cell Transplant. 2013;22(11):2063-77. doi: 10.3727/096368912X657855. Epub 2012 Oct 8.
citation: Paolella F, Manferdini C, Gabusi E, Gambari L, Filardo G, Kon E, Mariani E, Lisignoli G. Effect of microfragmented adipose tissue on osteoarthritic synovial macrophage factors. J Cell Physiol. 2019 Apr;234(4):5044-5055. doi: 10.1002/jcp.27307. Epub 2018 Sep 6.