Adipose Derived Mesenchymal Stem Cell Characteristics in Anal Fistulas

Perianal Fistula Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04834609
• Other study ID #: AT-MSCs_Anal fistulas
• Status: Completed
• Phase: N/A
• Start date: January 2015
• Est. completion date: February 2021

Study information

• Verified date: March 2021
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: February 2021
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Adipose Tissue
• Fistula
• Perianal Fistula
• Rectal Fistula
• Tissue Transplantation

Intervention

Procedure:
• Injection of autologous adipose tissue in anal fistula

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
University of Aarhus	UiT The Arctic University of Norway, University of Southern Denmark

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Investigation of cell proliferation of AT-MSCs	Cell proliferation of AT-MSCs evaluated as number of cells/per day	At start of treatment
Primary	Investigation of differentiation potential of AT-MSCs to differentiate into adipocyte	Differentiation potential of AT-MSCs: to differentiate into adipocyte measured by Oil-Red O staining and gene expression of adipogenic markers (PPARg and LPL normalized to housekeeping gene beta actin) presented as a Fold change to undifferentiated cells (arbitrary units)	At start of treatment
Primary	Investigation of differentiation potential of AT-MSCs to differentiate into osteoblast	Differentiation potential of AT-MSCs: to differentiate into osteoblast measured by Alizarin S staining and gene expression of osteogenic markers (BGALP and RUNX2 normalized to housekeeping gene beta actin) presented as a Fold change to undifferentiated cells (arbitrary units)	At start of treatment
Primary	Measurement of gene expression profile of AT-MSCs	Gene expression of proinflammatory (NFKB, TNFa, IL1B, IL6) and senescence associated molecules(CDKN2A, TP53, TGFB1, VEGFA, IFNG, IL6) of AT-MSCs in relation to the outcome of fistula treatment (i.e. comparison between responders and non-responders). The data are normalized to housekeeping gene beta actin (arbitrary units)	At start of treatment
Secondary	Healing of anal fistula after treatment	Clinical healing defined as closure of the internal and external fistula opening and no discharge evaluated as success rate of the healing in (%)	6 months after last injection of autologous adipose tissue
Secondary	Evaluation of fistula healing after treatment	A combination of Clinical and MRI healing defined as closure of the internal and external fistula opening and no discharge and no fluid filled fistula tracts on evaluated as success rate of the healing in (%)	6 months after last injection of autologous adipose tissue
Secondary	Functional gastroenterological outcome after treatment	Anal continence evaluated as the St. Mark's Score (0-24)	6 months after last injection of autologous adipose tissue
Secondary	Defecation disorder evaluation after treatment	Defecation disorders evaluated as Altomare Obstructed Defecation Score (0-31)	6 months after last injection of autologous adipose tissue
Secondary	Functional urological outcome after treatment	Urinary incontinence evaluated as ICIQ-UI-SF (0-21)	6 months after last injection of autologous adipose tissue