Conservative Treatment of Gastrointestinal Fistulas by Endoscopic Injection of tSVFem

Gastrointestinal Fistula Clinical Trial

— tSVFem  

Official title:

Conservative Treatment of Gastrointestinal Fistulas by Endoscopic Injection of Emulsified Adipose Tissue Stromal Vascular Fraction (tSVFem)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04670276
• Other study ID #: 3127 prot.num 0043082/20
• Status: Recruiting
• Phase: N/A
• Start date: November 2, 2020
• Est. completion date: April 10, 2022

Study information

• Verified date: December 2020
• Source: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Contact: Dania Nachira, MD
• Phone: 00390630155692
• Email: dania.nachira[@]policlinicogemelli.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Gastrointestinal (GI) fistula is a complex condition with high mortality and requiring a multidisciplinary management.

The aim of this study is to exploit the regenerative-tissue capacities of autologous emulsified adipose tissue-derived stromal vascular fraction (tSVFem, widely used in other medical fields - like plastic surgery -for different purposes) harvested and delivered locally by endoscopy to close the GI fistula.

The proposed technique for the treatment of GI fistulas with tSVFem requires a minimal, inexpensive, easily reproducible mechanical manipulation of autologous adipose tissue without necessity of any enzymatic digestion or cell expansion.

Description:

Gastrointestinal fistula may be a life-threatening condition caused by several types of injuries (iatrogenic, traumatic, post-operative), requiring complex and multidisciplinary management. To date, no clear guidelines have been drawn up for the treatment, that may include a conservative, minimally invasive, or major surgical approach depending on the patient's specific clinical characteristics. Furthermore, patients with fistulas are often fragile, and surgical treatments are highly risky and invasive. Less invasive treatments such as stenting, endoluminal endoscopic vacuum therapy and suturing are widely employed, but these treatments often require long hospitalization, highly skilled operators, without certain results and with high rates of complications.

The aim of this study is to exploit the regenerative-tissue capacities of autologous emulsified adipose tissue-derived stromal vascular fraction (tSVFem, widely used in other medical fields - like plastic surgery -for different purposes) harvested and delivered locally by endoscopy to close the GI fistula. Indeed, the anti-inflammatory and regenerative-tissue promoting effects of tSVFem may safely promote rapid and effective tissue healing as alternative, and in this setting they were not investigated before. Fistulas are often long-standing chronic conditions, thus healing mechanisms are delayed and subverted in favor of inflammation and fibrosis, resembling chronic inflammatory diseases. Delivery of tSVFem is a promising new approach that promotes healing in virtue of its immunosuppressive, immunomodulatory, pro-angiogenic and regenerative potentials. Since the grafted material used in this study is autologous, there is no risk for rejection. All the procedures are performed under general anesthesia with orotracheal intubation or laryngeal mask. Approximately 30 cc of fat are harvested from the superficial layer of subcutaneous tissue by a 2.1 mm microcannula with 4, 1-mm size holes, arranged in a single raw, to get the so-called "microfat". Twenty cc of the harvested microfat are mechanical emulsified by sequential passages through 2.4mm and 1.2mm filters, and a 600/400 μm disposable filtering device.

Then the material is centrifuged at 3000 rounds for three minutes, obtaining the tSVFem after removal of supernatant fraction and oil released upon mature adipocytes mechanical disruption.

Subsequently, an endoscopy is performed to inject 10 cc of microfat into the fistula (through a 6-French catheter) until it was completely filled. Then, with a 22 Gauge endoscopic needle, a total of 1-2 cc of tSVFem were injected into the submucosa of the 4 quadrants of the fistula borders, to obliterate it completely.

A radiologic and endoscopic control at day-7 is done to evaluate complete healing of the fistula.

The technique proposed by the investigators for the treatment of GI fistulas with tSVFem requires a minimal, inexpensive, easily reproducible mechanical manipulation of autologous adipose tissue without necessity of any enzymatic digestion or cell expansion.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 10, 2022
• Est. primary completion date: March 2, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Patients affected by GI fistulas, not fit for surgical treatments of after failure of conventional conservative treatments

Exclusion Criteria:

• Enteroenteric fistulas

• Patients who do not sign informed consent form

Related Conditions & MeSH terms

• Digestive System Fistula
• Fistula
• Gastrointestinal Fistula

Intervention

Procedure:
• injection of emulsified adipose tissue stromal vascular fraction
Endoscopic injection of 10 cc of autologous microfat into the fistula (through a 6-French catheter), until it was completely filled, and a total of 1-2 cc of tSVFem (through a 22G endoscopic needle) into the submucosa of the 4 quadrants of the fistula borders, to obliterate it completely.

Locations

Country	Name	City	State
Italy	Fondazione Policlinico Agostino Gemelli IRCCS	Roma

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Country where clinical trial is conducted

Italy, 

References & Publications (8)

Angelo Trivisonno, Marc Abecassis, Massimo Monti et al. Adipose Tissue: From Energy Reservoir to a Source of Cells for Epithelial Tissue Engineering. In: Stem Cells in Aesthetic Procedures: Springer Berlin Heidelberg,2014:303-326

Brangewitz M, Voigtländer T, Helfritz FA, Lankisch TO, Winkler M, Klempnauer J, Manns MP, Schneider AS, Wedemeyer J. Endoscopic closure of esophageal intrathoracic leaks: stent versus endoscopic vacuum-assisted closure, a retrospective analysis. Endoscopy. 2013 Jun;45(6):433-8. doi: 10.1055/s-0032-1326435. Epub 2013 Jun 3. — View Citation

Brinster CJ, Singhal S, Lee L, Marshall MB, Kaiser LR, Kucharczuk JC. Evolving options in the management of esophageal perforation. Ann Thorac Surg. 2004 Apr;77(4):1475-83. Review. — View Citation

Ceccarelli S, Pontecorvi P, Anastasiadou E, Napoli C, Marchese C. Immunomodulatory Effect of Adipose-Derived Stem Cells: The Cutting Edge of Clinical Application. Front Cell Dev Biol. 2020 Apr 17;8:236. doi: 10.3389/fcell.2020.00236. eCollection 2020. Review. — View Citation

Kuehn F, Loske G, Schiffmann L, Gock M, Klar E. Endoscopic vacuum therapy for various defects of the upper gastrointestinal tract. Surg Endosc. 2017 Sep;31(9):3449-3458. doi: 10.1007/s00464-016-5404-x. Epub 2017 Jan 11. Review. — View Citation

Panés J, García-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, Dignass A, Nachury M, Ferrante M, Kazemi-Shirazi L, Grimaud JC, de la Portilla F, Goldin E, Richard MP, Leselbaum A, Danese S; ADMIRE CD Study Group Collaborators. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial. Lancet. 2016 Sep 24;388(10051):1281-90. doi: 10.1016/S0140-6736(16)31203-X. Epub 2016 Jul 29. — View Citation

Porziella V, Nachira D, Boškoski I, Trivisonno A, Costamagna G, Margaritora S. Emulsified stromal vascular fraction tissue grafting: a new frontier in the treatment of esophageal fistulas. Gastrointest Endosc. 2020 Dec;92(6):1262-1263. doi: 10.1016/j.gie.2020.06.019. Epub 2020 Jul 4. — View Citation

Trivisonno A, Nachira D, Boškoski I, Calcagni F, Tringali A, Costamagna G, Margaritora S, Porziella V. Autologous Fat Grafting Restores Soft-tissue Contour Deformities after Vascular Anomaly: Widening the Horizons of Employment of Autologous Fat Grafting. Plast Reconstr Surg Glob Open. 2019 Nov 27;7(11):e2518. doi: 10.1097/GOX.0000000000002518. eCollection 2019 Nov. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fistula healing	Rate of healing of fistula at endoscopy and gastrografin swallow	7 days after the injection procedure of tSVFem
Secondary	Incidence of treatment adverse events and complications	To evaluate the percentage of patients that developed adverse events or any complications during and after the treatment proposed	During the procedure, 7 days after and at 1-2 month follow-up