Perianal Fistula Treatment With Autologous Adipose Tissue Injection

NCT ID: NCT03913910

Last Updated: 2019-05-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-02-01

Study Completion Date

2020-06-30

Brief Summary

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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

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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.

Conditions

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Perianal Fistula

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Lipogems

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

Lipogems

Intervention Type PROCEDURE

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.

Interventions

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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.

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Azienda Ospedaliero, Universitaria Pisana

OTHER

Sponsor Role lead

Responsible Party

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Gabriele Naldini

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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AOU Pisana - Cisanello

Pisa, Tuscany, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Gabriele Naldini, MD

Role: CONTACT

+39050997802

Alessandro Sturiale, MD

Role: CONTACT

+39050997814

Facility Contacts

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Gabriele Naldini, MD

Role: primary

Alessandro Sturiale

Role: backup

0039 3311372249

References

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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.

Reference Type BACKGROUND
PMID: 29453515 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27547712 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27547374 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27236668 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30255987 (View on PubMed)

Garcia-Contreras M, Messaggio F, Mendez AJ, Ricordi C. Metabolomic changes in human adipose tissue derived products following non-enzymatic microfacturing. Eur Rev Med Pharmacol Sci. 2018 May;22(10):3249-3260. doi: 10.26355/eurrev_201805_15088.

Reference Type BACKGROUND
PMID: 29863273 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26240640 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23051701 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30187478 (View on PubMed)

Other Identifiers

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AOUPisana_1

Identifier Type: -

Identifier Source: org_study_id

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