Clinical trial NCT04834609: Adipose Derived Mesenchymal Stem Cell Characteristics in Anal Fistulas
Official title: Identification of Molecular Differences of Adipose-derived Mesenchymal Stem Cells Between Non- Responders and Responders in Treatment of Transsphincteric Perianal Fistulas Using Autologous Fat Graft Injection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Perianal Fistula
Adipose Tissue
Tissue Transplantation
Keywords: autologous adipose tissue, mesenchymal stem cells, perianal fistula
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: University of Southern Denmark
name: UiT The Arctic University of Norway
First posted: 2021-04-08
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study investigated the cellular and molecular characteristics of AT-MSCs obtained from autologous AT therapy in patients with high transphincteric perianal fistulas of crytoglandular origin. Adipose tissue was injected into anal fistulas. Characteristics of adipose tissue mesenchymal stemcells (AT-MSC) was investigated and compared in patients with fistula that healed after the treatment (responders) to patients who failed to heal (non-responders)

Detailed description: Injection with allogene or autologous stem cells has been reported to be efficient treatment of perianal fistulas. An alternative to this treatment could be injection with freshly collected autologous adipose tissue. In this study 27 patients with cryptoglandular anal fistulas were treated with freshly collected autologous adipose tissue.A clinical assessment of the patient prior to inclusion was undertaken and a loose seton placed for at least 6 weeks prior to fat injection. An MRI of the pelvis was performed before inclusion. Fistulas with secondary tracts and/or cavities were excluded. The operation was performed in one procedure including liposuction and injection of adipose tissue. A sample of adipose tissue from all 27 patients was analyzed. AT-MSCs were isolated and characterized using cellular and molecular analyses. Clinical and MRI-scanning evaluation of fistula healing and evaluation of ano-rectal function was performed after 6 months. AT-MSCs phenotype was compared between responders and non-responders with respect to fistula healing. The evaluation of the AT-MSCs was performed in a blinded manner.

Eligibility criteria: Inclusion Criteria:

* high trans-sphincteric fistulas
* fistula confirmed and classified by an MRI.
* seton (\> 6 weeks) prior to fat injection
* informed, written consent.

Exclusion Criteria:

Anovaginal fistula

* Active sepsis
* IBD, immunodeficiency, prior pelvic irradiation and malignancy
* Insulin dependent diabetes
* More than 4 prior attempts of fistula closure
* Tobacco smoking or nicotine substitution 8 weeks prior to fat injection.
* Pregnancy
* Psychiatric disorders
* BMI ≥ 35 or BMI\<20
* Active tuberculosis
* Patient less than 18 years
* Unable to undergo MRI

Primary outcomes:
measure: Investigation of cell proliferation of AT-MSCs
timeFrame: At start of treatment
measure: Investigation of differentiation potential of AT-MSCs to differentiate into adipocyte
timeFrame: At start of treatment
measure: Investigation of differentiation potential of AT-MSCs to differentiate into osteoblast
timeFrame: At start of treatment
measure: Measurement of gene expression profile of AT-MSCs
timeFrame: At start of treatment
Secondary outcomes:
measure: Healing of anal fistula after treatment
timeFrame: 6 months after last injection of autologous adipose tissue
measure: Evaluation of fistula healing after treatment
timeFrame: 6 months after last injection of autologous adipose tissue
measure: Functional gastroenterological outcome after treatment
timeFrame: 6 months after last injection of autologous adipose tissue
measure: Defecation disorder evaluation after treatment
timeFrame: 6 months after last injection of autologous adipose tissue
measure: Functional urological outcome after treatment
timeFrame: 6 months after last injection of autologous adipose tissue
Other outcomes:
Locations:
Study officials:
References:
citation: Tencerova M, Lundby L, Buntzen S, Norderval S, Hougaard HT, Pedersen BG, Kassem M. Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas. Stem Cell Res Ther. 2021 Nov 24;12(1):586. doi: 10.1186/s13287-021-02644-8.