- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04326907
Treatment of Complex Anal Fistulas Using Centrifuged Adipose Tissue Containing Progenitor Cells (CAT)
Efficacy and Safety of Treatment of Complex Anal Fistulas Not Associated With Crohn's Disease Using Centrifuged Adipose Tissue Containing Progenitor Cells: a Randomized Controlled Clinical Trial
In the treatment of complex anal fistulas transplant of freshly collected autologous adipose tissue mechanically fragmented or centrifuged adipose tissue (CAT) might be an alternative to in vitro expanded autologous or allogeneic adipose-derived stem cells, showing remarkable efficacy in diverse therapeutic indications.
The aim of our study is to evaluate randomly the efficacy and safety of the use of CAT in the healing process of complex anal fistulas, except for Crohn's disease (CD) related fistulas.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This monocentric randomized controlled study was designed to test the efficacy and safety of injection of CAT for treatment of complex fistula-in ano, not associated with CD . The study was conducted at the Second Surgical Unit of the University Hospital of Ferrara, located in the North East of Italy. All consecutive patients referred to our clinic with complex anal fistula were screened. Patients were enrolled from May 2016 through May 2019.
Eligible patients were randomly assigned, according to a 1:1 scheme, to receive treatment with or without CAT (120 patients totally). The primary endpoint was defined as the proportion of patients whose fistula was completely healed within 4 weeks after surgery. Fistula healing was defined as the absence of any anal symptom, with no discharge from the fistula and a closed external opening confirmed on clinical evaluation. Fistula healing was eventually confirmed by a pelvic MRI at 3 months after surgery.Moreover, we analyzed postoperative pain measured by Visual Analogue Scale for 2 weeks after surgery to evaluate whether CAT injection could modulate pain, and recurrence at 6 months to evaluate the long-term efficacy of CAT injection.
Faecal continence was assessed before surgery and at 6-months follow-up visit using the Cleveland Clinical Florida Fecal Incontinence (CCF-FI) questionnaire. Adipose tissue from periombelical or lateral abdomen was harvested from these patients by liposuction to prepare CAT using Coleman's technique.Complex anal fistulas were treated by conventional surgery. Once the seton (present in the most of patients) was removed, after identification of internal opening, necrotic and inflamed tissues were excised using a "cone-like" fistulectomy or debrided with a wire brush to remove granulation tissue by the help of fistuloscope (VAAFT modified, without destroying the fistulous track with monopolar electrode). Before CAT injection, the internal opening was treated in two ways: by simply closing it using 2-0 Vicryl stitches on the muscular and mucosal layers or by performing a mucosal advancement rectal flap.
CAT was injected into the submucosal layer surrounding the internal opening, and around the fistula tract wall (in case of VAAFT modified) or inside the perianal wound after fistulectomy, using a 1-mL syringe equipped with a 22-gauge and 30-mm length needle, dividing injections at all quadrants of fistula wall, or distributing the CAT inside the perianal wound, at different levels by using multiple passes from the internal to the external openings until there was firm swelling surrounded the fistula tract. The external opening was approximated loosely with a suture to allow drainage of the fistula, but not extrusion of the centrifuged adipose tissue. The amount of product injected may vary depending on the total amount harvested but it should be not less than 10 ml. Patients were assessed for fistula healing, pain (VAS) and AEs at 1 week, 2 weeks, 4 weeks, 8 weeks, three months, and 6 months after treatment. Assessment consisted of clinical examination and AEs and VAS registration. Pelvic MRI was performed at 3 months after surgery. The Cleveland Clinical Florida Fecal Incontinence (CCF-FI) questionnaire was administered before surgery and at 6-months follow-up visit. At the final visit patients were also asked about their overall satisfaction with the procedure, with ratings from very satisfied to very dissatisfied.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Ferrara, Italy, 44121
- Simona Ascanelli
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Patients aged 18 years or older with complex perianal fistulas
Exclusion Criteria:
Inflammatory bowel diseases, Crohn's Disease (CD) or Ulcerative Colitis (UC) Hepatitis B or C virus Infection with Human immunodeficiency virus Surgery for a malignant tumor during the previous 5 years (excluding in situ carcinoma) Previous pelvic radiotherapy Autoimmune disease Active tuberculosis Symptoms of septicemia Breastfeeding or pregnant women Women unwilling to use contraception during the study Psychiatric disorders Alcoholism Drug dependency Allergy to local anesthetics
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CAT injection group
After fistulectomy for complex anal fistula, CAT (harvested from abdominal subcutaneous adipose tissue by Coleman's procedure) was injected into the tissue surrounding the internal opening, and inside the perianal wound obtained after fistulectomy.
|
Collection and injection of autologous adipose tissue in complex anal fistulas in one surgical step under locoregional or general anesthesia.
|
No Intervention: No CAT injection group
Patients of this group were treated with anal fistulectomy without CAT injection.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Fistula healing rate within 6 months after surgery
Time Frame: up to 6 months
|
Fistula healing was defined as the absence of any anal symptom, with no discharge from the fistula and a closed external opening confirmed on clinical evaluation.
Fistula healing was eventually confirmed by a pelvic MRI at 3 months after surgery
|
up to 6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety of autologous adipose tissue injection
Time Frame: 4 weeks
|
Safety was evaluated by the overall incidence and severity of Adverse Events (AEs) up to 4 weeks following surgery.
|
4 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
postoperative pain
Time Frame: 2 weeks
|
postoperative pain measured by Visual Analogue Scale (0-10) for 2 weeks after surgery to evaluate whether CAT injection could modulate pain
|
2 weeks
|
recurrence at 6 months
Time Frame: 6 months
|
to evaluate the long-term efficacy of CAT injection
|
6 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Simona Ascanelli, MD, University Hospital Ferrara
Publications and helpful links
General Publications
- Zollino I, Campioni D, Sibilla MG, Tessari M, Malagoni AM, Zamboni P. A phase II randomized clinical trial for the treatment of recalcitrant chronic leg ulcers using centrifuged adipose tissue containing progenitor cells. Cytotherapy. 2019 Feb;21(2):200-211. doi: 10.1016/j.jcyt.2018.10.012. Epub 2018 Dec 22.
- Garcia-Olmo D, Garcia-Arranz M, Herreros D, Pascual I, Peiro C, Rodriguez-Montes JA. A phase I clinical trial of the treatment of Crohn's fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum. 2005 Jul;48(7):1416-23. doi: 10.1007/s10350-005-0052-6.
- Garcia-Olmo D, Herreros D, Pascual I, Pascual JA, Del-Valle E, Zorrilla J, De-La-Quintana P, Garcia-Arranz M, Pascual M. Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Dis Colon Rectum. 2009 Jan;52(1):79-86. doi: 10.1007/DCR.0b013e3181973487.
- Limura E, Giordano P. Modern management of anal fistula. World J Gastroenterol. 2015 Jan 7;21(1):12-20. doi: 10.3748/wjg.v21.i1.12.
- Aust L, Devlin B, Foster SJ, Halvorsen YD, Hicok K, du Laney T, Sen A, Willingmyre GD, Gimble JM. Yield of human adipose-derived adult stem cells from liposuction aspirates. Cytotherapy. 2004;6(1):7-14. doi: 10.1080/14653240310004539.
- Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002 Dec;13(12):4279-95. doi: 10.1091/mbc.e02-02-0105.
- 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.
- Dige A, Hougaard HT, Agnholt J, Pedersen BG, Tencerova M, Kassem M, Krogh K, Lundby L. Efficacy of Injection of Freshly Collected Autologous Adipose Tissue Into Perianal Fistulas in Patients With Crohn's Disease. Gastroenterology. 2019 Jun;156(8):2208-2216.e1. doi: 10.1053/j.gastro.2019.02.005. Epub 2019 Feb 14.
- Laureti S, Gionchetti P, Cappelli A, Vittori L, Contedini F, Rizzello F, Golfieri R, Campieri M, Poggioli G. Refractory Complex Crohn's Perianal Fistulas: A Role for Autologous Microfragmented Adipose Tissue Injection. Inflamm Bowel Dis. 2020 Jan 6;26(2):321-330. doi: 10.1093/ibd/izz051.
- Pu LLQ, Coleman SR, Cui X, Ferguson REH Jr, Vasconez HC. Autologous fat grafts harvested and refined by the Coleman technique: a comparative study. Plast Reconstr Surg. 2008 Sep;122(3):932-937. doi: 10.1097/PRS.0b013e3181811ff0.
- Ibatici A, Caviggioli F, Valeriano V, Quirici N, Sessarego N, Lisa A, Klinger F, Forcellini D, Maione L, Klinger M. Comparison of cell number, viability, phenotypic profile, clonogenic, and proliferative potential of adipose-derived stem cell populations between centrifuged and noncentrifuged fat. Aesthetic Plast Surg. 2014 Oct;38(5):985-93. doi: 10.1007/s00266-014-0372-9. Epub 2014 Jul 23.
- Park SR, Kim JW, Jun HS, Roh JY, Lee HY, Hong IS. Stem Cell Secretome and Its Effect on Cellular Mechanisms Relevant to Wound Healing. Mol Ther. 2018 Feb 7;26(2):606-617. doi: 10.1016/j.ymthe.2017.09.023. Epub 2017 Oct 5.
- 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.
- Ascanelli S, Zamboni P, Campioni D, Grazia Sibilla M, Chimisso L, Zollino I, Valpiani G, Carcoforo P. Efficacy and Safety of Treatment of Complex Idiopathic Fistula-in-Ano Using Autologous Centrifuged Adipose Tissue Containing Progenitor Cells: A Randomized Controlled Trial. Dis Colon Rectum. 2021 Oct 1;64(10):1276-1285. doi: 10.1097/DCR.0000000000001924.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- UHFerrara160597
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Anal Fistula
-
Zagazig UniversityCompletedTranssphincteric Anal FistulaEgypt
-
F Care Systems NVNot yet recruiting
-
Chinese University of Hong KongTerminated
-
Societa Italiana di Chirurgia ColoRettaleTerminated
-
Mansoura UniversityUnknownVideo Assisted Anal Fistula TreatmentEgypt
-
Groupe Hospitalier Paris Saint JosephCompletedComplex Anal FistulaFrance
-
Assiut UniversityActive, not recruiting
-
University Hospital, Clermont-FerrandUnknown
-
Dr Benjamin NEBBOTSuspended
-
University of Southern DenmarkOdense University HospitalCompleted
Clinical Trials on Autologous centrifuged adipose tissue (CAT) injection after anal fistulectomy
-
University of AarhusUniversity of Southern Denmark; UiT The Arctic University of NorwayCompletedPerianal Fistula | Adipose Tissue | Tissue Transplantation
-
Lilli LundbyCompletedCrohn Disease | Perianal Fistula | Tissue Transplantation
-
Aestique Medical CenterCompletedOsteo Arthritis KneeUnited States
-
Istituto Ortopedico RizzoliRecruitingBilateral Knee Osteoarthritis | Autologous Adipose TissueItaly
-
Hospital Mutua de TerrassaRecruiting
-
South Ural State Medical UniversityCompletedRectovaginal FistulaRussian Federation
-
Nagoya UniversityCompletedUrinary Incontinence , StressJapan
-
Lipogems International spaRecruitingOsteoarthritis, KneeItaly
-
Medical University of WarsawNot yet recruitingKnee Osteoarthritis | Chondropathy
-
University of Southern CaliforniaUnknown