A Novel Method for Chronic Anal Fissure Treatment

December 10, 2015 updated by: Katarina Andjelkov, Clinical Centre of Serbia

A Novel Method for Chronic Anal Fissure Treatment: Adipose Derived Regenerative Cells - A Pilot Study

Investigators performed a prospective pilot study to test the feasibility and safety of autologous adipose derived regenerative cell (ADRC) transplantation in treatment of anal fissures. The study included 6 patients with chronic anal fissures with symptoms that had an average duration of 24 months. All patients were candidates for surgical treatment as all previous conservative treatments were unsuccessful. The pain level was measured using the VAS scale and was recorded before the treatment and on every consultation following the treatment.

The initial hypothesis is that application of ADRCs may be an alternative to lateral sphincterotomy and a reliable procedure to avoid fecal incontinence.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This prospective pilot study includes 6 patients suffering from chronic anal fissure. All patients were previously treated with different local applications of glyceryl trinitrate or topical Xylocaine gel. Some patients took oral analgesics as a concomitant therapy for additional pain control. None of the patient received neither topical calcium channel blockers nor Botulinum toxin injection due to the unavailability.

The primary outcome measured is "time to complete cessation of anal pain". The secondary outcome includes the healing of chronic anal fissure defined as "time to complete epithelization".

The study was approved by the Ethics Committee of the First Surgical Clinic, Faculty of Medicine, and University of Belgrade. The study was performed in accordance with the Declaration of Helsinki and current Good Clinical Practices. All patients gave the written informed consent prior to the participation.

Physical examination and the detail medical history has been taken by an experienced colorectal surgeon. Pain assessment is quantified using the visual analog scale (VAS) before the treatment and during each postoperative outpatient visit. Bowel continence has been also assessed using Wexner fecal incontinence score prior to the treatment and during each postoperative outpatient visit. The liposuction procedure has been performed performed under the combination of local anesthesia and moderate sedation/general anesthesia. The mixture of 180 mL saline solution, 1mL Epinephrine (1:10,000) and 20 mL of 2% lidocaine is injected in the subcutaneous layer of the abdominal wall to allow the tumescence and to decrease the blood loss. The manual liposuction procedure has been carried out through two or three small incisions using Sforza harvester (Tulip® medical products, San Diego, USA). Approximately 150-200 mL of raw lipoaspirate is obtained from each patient. The harvest site is then covered with a pressure dressing for 10 days to reduce swelling and hematoma. The closed system PureGraft® 250mL (PureGraft®, Solana Beach, California, USA) has been used used to collect the specimen. The specimen is transferred within 15 min to the BelPrime Clinic laboratory where the Celution® 800/CRS system (Cytori Therapeutics, Inc. San Diego, California, USA) is applied to process the lipoaspirate in order to obtain ADRCs. The Celution® 800/CRS system is a closed automated medical device that helps to separate blood and fat. The system will then digests fat using the proprietary enzyme reagent Celase 835/CRS (Cytori Therapeutics, Inc. San Diego, California, USA) to release the stromal vascular fraction (SVF). SVF is subsequently concentrated by a short centrifugation and then automated wash cycles to obtain the ADRC fraction. This 90 to 120-minute process provides approximately 5mL of pellet. A few drops of the obtained pellet were immediately used for cell counting (ChemoMetec A/S DK-3450, Allerod, Denmark).

The second procedure has been performed in lithotomy position. Intravenous prophylactic antibiotic (1gm Metronidazol) are administered. After the careful and gentle anal examination, anal fissure is first curetted using a small size curette. The pellet is divided into two parts. The first 2mL of the pellet is mixed with 8mL of the lipid part of the lipoaspirate purified by Puregraft® 50 system. This solution (10mL) is injected subcutaneously into the edge of the fissure using the criss-cross lattice technique by Tulip® 1,2 mm injector. The rest of the pellet, (approximately 2-5mL), is infiltrated directly into the fissure base (internal anal sphincter) using a 20G needle. No laxatives or stool softener is prescribed. Patients have been discharged from the hospital a few hours after the procedure.

Patients are followed up weekly by telephone interview during the first 2 months, then monthly up to 12 months after the procedure. The outpatient visits are scheduled monthly until 9 months to ensure the healing of anal fissure. Visual analogue scale (VAS) score and Wexner fecal incontinence score [31] are also recorded.

Study Type

Interventional

Enrollment (Actual)

6

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

16 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • The inclusion criteria were adults (>18 years) with chronic (> 8 weeks of conservative therapy) anal fissures

Exclusion Criteria:

  • The exclusion criteria were autoimmune diseases, inflammatory bowel disease, presence of malignant or chronic infectious disease, or immunosuppressive therapy.

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: ADRCs therapy

Infiltration with 20mL Lidocaine 2% and Epinephrine 1:100 000. Liposuction will be done from the abdomen using Tulip cannulas. Fat will be processed with Celution system.

Isolated ADRCs will be administered in chronic anal fissures.
Other: ADRCs therapy
Patients with chronic anal fissures will receive one treatment of local injections of fat enriched with adipose derived regenerative cells starting from December 2014.
Device: Celution
Adipose derived regenerative cell isolation
Device: Tulip cannulas
Lipoaspiration
Other: 20mL Lidocaine 2% and Epinephrine 1:100 000
Infiltration prior to liposuction
Other Names:
  • Xylocaine 2% and adrenaline 1:100 000

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Time to complete cessation of anal pain
Time Frame: 33 days
33 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Time to complete epithelization
Time Frame: 3 months
3 months

Collaborators and Investigators

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

Sponsor

Clinical Centre of Serbia

Investigators

  • Principal Investigator: Katarina Andjelkov, MD, PhD, Clinical Centre Serbia

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

December 1, 2014

Primary Completion (Actual)

February 1, 2015

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

December 2, 2015

First Submitted That Met QC Criteria

December 10, 2015

First Posted (Estimate)

December 11, 2015

Study Record Updates

Last Update Posted (Estimate)

December 11, 2015

Last Update Submitted That Met QC Criteria

December 10, 2015

Last Verified

December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCS-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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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