Adipose Derived Mesenchymal Stem Cell Characteristics in Anal Fistulas

April 6, 2021 updated by: University of Aarhus

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

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)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Injection with adipose tissue
Injection of freshly collected autologous adipose tissue
Procedure: Injection of autologous adipose tissue in anal fistula

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Investigation of cell proliferation of AT-MSCs
Time Frame: At start of treatment
Cell proliferation of AT-MSCs evaluated as number of cells/per day
At start of treatment
Investigation of differentiation potential of AT-MSCs to differentiate into adipocyte
Time Frame: At start of treatment
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
Investigation of differentiation potential of AT-MSCs to differentiate into osteoblast
Time Frame: At start of treatment
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
Measurement of gene expression profile of AT-MSCs
Time Frame: At start of treatment
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Healing of anal fistula after treatment
Time Frame: 6 months after last injection of autologous adipose tissue
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
Evaluation of fistula healing after treatment
Time Frame: 6 months after last injection of autologous adipose tissue
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
Functional gastroenterological outcome after treatment
Time Frame: 6 months after last injection of autologous adipose tissue
Anal continence evaluated as the St. Mark's Score (0-24)
6 months after last injection of autologous adipose tissue
Defecation disorder evaluation after treatment
Time Frame: 6 months after last injection of autologous adipose tissue
Defecation disorders evaluated as Altomare Obstructed Defecation Score (0-31)
6 months after last injection of autologous adipose tissue
Functional urological outcome after treatment
Time Frame: 6 months after last injection of autologous adipose tissue
Urinary incontinence evaluated as ICIQ-UI-SF (0-21)
6 months after last injection of autologous adipose tissue

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aarhus

Collaborators

University of Southern Denmark
UiT The Arctic University of Norway

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2015

Primary Completion (Actual)

October 1, 2017

Study Completion (Actual)

February 1, 2021

Study Registration Dates

First Submitted

March 22, 2021

First Submitted That Met QC Criteria

April 6, 2021

First Posted (Actual)

April 8, 2021

Study Record Updates

Last Update Posted (Actual)

April 8, 2021

Last Update Submitted That Met QC Criteria

April 6, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AT-MSCs_Anal fistulas

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

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