Treatment of Fecal Incontinence Using Allogenic-Adipose-derived Mesenchymal Stem Cells: A Prospective, Dose Escalation, Randomized, Placebo-controlled, Parallel-group, Single-blind, Single-center Pilot Study

Study Overview
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Brief Summary
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Purpose: The investigators aimed to investigate the safety and efficacy in the treatment of fecal incontinence by injection of ALLO-ASC into the anal sphincter. Method Safety test of allogenic ASCs injection Efficacy test of allogenic ASCs injection

Detailed Description
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Background: Fecal incontinence is a distressing condition with recurrent uncontrolled passage of fecal material. Although fecal incontinence is developed by multifactorial causes, treatments were limited in medical or surgical methods. According to the recent studies of stem cell regeneration, it is reported that human adipose-derived stem cells have plentiful capacity in muscle regeneration, which had the efficacy to treat Crohn's fistulas. Therefore, the investigators hypothesized that the capability of muscle regeneration of allogenic-adipose-derived mesenchymal stem cells (ALLO-ASC) can be used to treat degenerated anal sphincter, which leads to fecal incontinence. Purpose:The investigators aimed to investigate the safety and efficacy in the treatment of fecal incontinence by injection of ALLO-ASC into the anal sphincter. Method Safety test of allogenic ASCs injection In the first year, the investigators will investigate the safety of ALLO-ASC injection by a dose escalation study. Patients are sequentially enrolled into three groups, which are composed of three patients each. They are treated with an injection of ALLO-ASC to the anal sphincter for 3x107 cells/ml (group 1), 6x107 cells/ml (group 2), 9x107 cells/ml (group 3), respectively. After receiving the ALLO-ASC injection, patients will receive a physical examination, a serologic and immunologic response test (CD4/CD8) with an assessment of the Wexner score, patient satisfaction survey, WHO toxicity scale, adverse events, anorectal manometry and endorectal ultrasound at 1, 4, 8 weeks, 4, 6, 9, and 12 months in the outpatient clinic. The response of ALLO-ASC injection is assessed at 8 weeks after an injection and the most effective dose is determined among the groups. Efficacy test of allogenic ASCs injection In the second year, the investigators will assess the efficacy of the ALLO-ASC injection comparing the ALLO-ASC injection group and the placebo group (0.9% normal saline injection) by a randomized, open-label, single-blind design. Each group is composed of six patients. Both the clinical assessment and follow-up period are identical with the first-year protocol.

Official Title
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Treatment of Fecal Incontinence Using Allogenic-Adipose-derived Mesenchymal Stem Cells: A Prospective, Dose Escalation, Randomized, Placebo-controlled, Parallel-group, Single-blind, Single-center Pilot Study

Conditions
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Fecal Incontinence

Intervention / Treatment
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* Biological: ALLO-ASC injection
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 19 years old Patients who received either medical therapy or biofeedback for fecal incontinence for more than 2 months with Wexner score ≥ 8 Transanal ultrasonography: presents a continuous fashion of anal sphincter Anal manometery: decreased anal pressures than normal level Negative for urine β-hCG in the screening test An informed consent form has been signed by the patient Exclusion Criteria: Participation in another clinical trial within 30 days History of anorectal surgery within the previous 6 months History of malignant tumor surgery within the previous 5 years (except for carcinoma in situ) Patients requiring anorectal surgical treatments History of artificial sphincter surgery History of vaginal delivery within 6 months Medical history of variant Creutzfeld-Jakobs disease or related diseases Allergy to bovine-derived materials, fibrin glue or anesthestics Autoimmune disease Active tuberculosis Pregnant or breastfeeding women Unwillingness to use contraceptive methods Patients with inflammatory bowel disease Alcohol or drug-abuse Use of cytotoxic agents within 30 days Patients who have severe constipation (<2 times/week), anal fistula, rectal prolapse, spinal cord injury, multiple sclerosis, Parkinson's disease Patients with one of hematologic disease, immunodeficieny, fever, acute disease or severe chronic disease

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALLO-ASC group<br>Allogenic-adipose-derived mesenchymal stem cell (ALLO-ASC) with fibrin glue injection to the anal sphincter | Biological: ALLO-ASC injection<br>* Allogenic-adipose-derived mesenchymal stem cells (ALLO-ASC) injection to the anal sphincter of patients with fecal incontinence<br>* Other names: ALLO-ASC;|
| Placebo Comparator: Normal saline group<br>0.9% normal saline with fibrin glue injection to the anal sphincter | Drug: Placebo<br>* 0.9% normal saline with fibrin glue injection to the anal sphincter of patients with fecal incontinence<br>* Other names: Normal saline with fibrin glue injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically measured abnormality of laboratory tests and adverse events | The investigators will assess the safety of allogenic-adipose-derived mesenchymal stem cell (ALLO-ASC) injection to the anal sphincter among the three experimental groups (group 1: 3x107 cells/ml; group 2: 6x107 cells/ml; group 3: 9x107 cells/ml)). | one year (12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Satisfaction as measured by Wexner Score | Improvement of Wexner Score at 12 months compared to baseline per each group. (The investigators will assess the efficacy of the ALLO-ASC injection comparing the ALLO-ASC injection group and the placebo group (0.9% normal saline injection) by a randomized, open-label, single-blind design.) | one year (12 months) |