Perianal FistulaNCT03913910
Perianal Fistula Treatment With Autologous Adipose Tissue Injection
An observational study of Perianal Fistula, run by Azienda Ospedaliero, Universitaria Pisana at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Perianal Fistula
- What is being tested?
- Lipogems
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- 1 Feb 2019to 30 Jun 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients with a diagnosis of transphincteric anal fistula that is not suitable to be laid open.
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
AOU Pisana - Cisanello
Pisa, Tuscany, 56124
Gabriele Naldini, MD, gabrielenaldini65@gmail.com
Alessandro Sturiale, 0039 3311372249, alexstur@yahoo.it
About this study
Official title: Treatment of Perianal Fistulas Through Injection of Autologous and Micro-fragmented Adipose Tissue: a Prospective Multicentre Study
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.
Read the 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.
- Conditions
- Perianal Fistula
- Being tested
- Lipogems
- Keywords
- Autologous micro-fragmented adipose tissue, Perianal fistula, Lipogems, Mesenchymal Stem Cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LipogemsProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Lipogems | Lipogems injection in the internal orifice, mucosal, submucosal and muscular layer, in the fistula tract and external orifice. Receives: Procedure: Lipogems |
What is being measured
The primary outcome is the main question the study is designed to answer.
Healing
Closing of the fistula tract (internal and external orifice)
Measured: 12 months
Secondary outcomes (5)
Safety collecting all types of adverse events
All types of adverse events intra-, peri-, or post-operative will be collected
Measured: 12 months
Pain assessed using the Visual Analogue Scale (VAS) for pain
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.
Measured: 12 months
Continence
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).
Measured: 12 months
Patient's satisfaction
Patient's satisfaction will be evaluated using a visual analogue scale 0-5, where 0 is no satisfaction and 5 is maximum satisfaction.
Measured: 12 months
Non inferiority compared with the Advancement flap technique
Non-inferiority will be determined comparing healing rate of Lipogems with retrospective data on the advancement flap.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2019
- Study start1 Feb 2019
- Primary completion31 Dec 2019 (estimated)
- Study completion30 Jun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Perianal FistulaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliero, Universitaria Pisana
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gabriele Naldini, Azienda Ospedaliero, Universitaria Pisana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03913910
- Sponsor's protocol ID
- AOUPisana_1
- Status last verified
- May 2019
- First submitted
- 11 Apr 2019
- Last updated
- 14 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 29453515Tremolada 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.
PubMed 27547712Ceserani 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.
PubMed 27547374Tremolada 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.
PubMed 27236668Vezzani 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.
PubMed 30255987Garcia-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.
PubMed 29863273Cestaro 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.
PubMed 26240640Bianchi 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.
PubMed 23051701Paolella 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.
PubMed 30187478
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Perianal Fistulas Through Injection of Autologous and Micro-fragmented Adipose Tissue: a Prospective Multicentre Study
- ClinicalTrials.gov ID
- NCT03913910
- Acronym / sponsor ID
- AOUPisana_1
- Conditions
- Perianal Fistula
- Keywords
- Autologous micro-fragmented adipose tissue, Perianal fistula, Lipogems, Mesenchymal Stem Cells
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Azienda Ospedaliero, Universitaria PisanaUniversity, hospital or other
- Study start
- 1 Feb 2019 (actual)
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 30 Jun 2020 (estimated)
- First posted
- 12 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lipogems | – | Procedure: LipogemsLipogems injection in the internal orifice, mucosal, submucosal and muscular layer, in the fistula tract and external orifice. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with a diagnosis of transphincteric anal fistula that is not suitable to be laid open.
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LipogemsAutologous 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. | Procedure or surgery | Lipogems |
Primary outcome
Healing
Time frame: 12 months
Closing of the fistula tract (internal and external orifice)
5 secondary outcomes
Safety collecting all types of adverse events
Time frame: 12 months
Pain assessed using the Visual Analogue Scale (VAS) for pain
Time frame: 12 months
Continence
Time frame: 12 months
Patient's satisfaction
Time frame: 12 months
Non inferiority compared with the Advancement flap technique
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2019.
- Background: PubMed 29453515Naldini 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.
- Background: PubMed 27547712Tremolada 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.
- Background: PubMed 27547374Ceserani 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.
- Background: PubMed 27236668Tremolada 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.
- Background: PubMed 30255987Vezzani 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.
- Background: PubMed 29863273Garcia-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.
- Background: PubMed 26240640Cestaro 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.
- Background: PubMed 23051701Bianchi 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.
- Background: PubMed 30187478Paolella 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Perianal Fistula, run by Azienda Ospedaliero, Universitaria Pisana at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Gabriele Naldini, MD (+39050997802, gabrielenaldini65@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Healing (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03913910, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2019.