Autologous Adipose-derived Stem Cells (ASCs) for the Treatment of Perianal Fistula in Crohn Disease: A Pilot Study

Summary

Crohn's disease is an immunologically mediated inflammatory bowel disease with a reported incidence of 4.0-7.0, 7.1, and 1.34 per 100,000 persons in Europe, the U.S., and Korea, respectively. Uncontrolled chronic inflammation finally causes various complications in intestine such as bowel obstruction, fistulas, abscesses, and anal fissures.

The incidence of perianal fistula was reported in 13%- 39% of patients with Crohn's disease. Medical treatment for Crohn's fistulae initially focused on surgical intervention accompanied by symptomatic treatment with antibiotics and immunosuppressants. The most serious problem after surgical intervention is the relatively high incidence of postoperative anal incontinence caused by sphincter injury during the procedure. Conversely, available pharmacological therapies for Crohn's fistulae based on biologic agents such as infliximab do not generally reach ideal goal of treatment (e.g., complete closure of the fistula). A high recurrence rate after treatment with infliximab has also been reported, even after long-term maintenance therapy, which suggests that infliximab monotherapy does not provide adequate healing.

The ACCENT II study demonstraded a complete fistula healing in 25% of patients. To reach a better clinical outcome, combination treatment with infliximab and surgical intervention is highly recommended for management of Crohn's fistulae. Nonetheless, even this strategy does not result in a satisfactory healing for many patients.

The ideal therapeutic goal of treatment is not only complete closure of the fistula without recurrence but also preservation of anal sphincter function. Unfortunately, currently available medical or surgical treatment is not likely to offer a cure for perianal fistulae and, as noted above, recurrence is frequently reported.

Together with active research in the field of bone marrow-derived mesenchymal stem cells (BM-MSCs) and hematopoietic stem cells, autologous or allogenic adipose tissue-derived stem cells (ASCs) have been studied for management of Crohn's disease and other disorders.

Of particular relevance to this study, ASCs could be considered to be safe and efficacious therapeutic tools for the treatment of Crohn's fistulae. Importantly, ASCs do not cause fecal incontinence after injection into the lesion site in Crohn's disease patients. A phase I dose-escalation clinical study with ASCs manufactured by Anterogen Co., Ltd. (Seoul, Korea) demonstrated the safety and therapeutic potential of these cells for the treatment of Crohn's fistulae. A phase II study demonstrated a good rate of cronh's related fistula closure using a ASCS injection.

Actually the best accepted treatment of Crohn related perianal fistula, is the surgical procedure in association whit medical therapy.

Conditions

• Perianal Fistula
• Crohn Disease

Interventions

PROCEDURE

ASCs injection

In the infiltration step, adrenalin in a saline solution is infiltrated using a 19-cm specially designed disposable blunt cannula. The aspiration step is performed by a luer-lock syringe connected to a disposable 19-cm blunt cannula. The harvested lipoaspirate can be progressively put into the device using multiple 10-cc syringes. Subsequently, in lithotomy position, a seton will be removed and a fistula tract will be thoroughly curetted and irrigated. After a mucosal flap preparing round the internal opening, cells will be injected in the perianal adipose tissue.

DEVICE

ASCs injection

In general anesthesia subcutaneous abdominal adipose tissue will be collected by LIPOGEMS system to prepare ASCS.

DEVICE

Closure of fistula tract.

A SALVECOLL-E paste will be injected into the fistula tract.

Sponsors & Collaborators

• Papa Giovanni XXIII Hospital

  lead OTHER

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-12-31

Primary Completion

2017-12-31

Completion

2018-12-31

Countries

• Italy

Study Locations