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

Yonsei University

Status and phase

Completed

Phase 1

Conditions

Fecal Incontinence

Treatments

Biological: ALLO-ASC injection

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT02384499

3-2014-0271

Details and patient eligibility

About

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
1. Safety test of allogenic ASCs injection
2. Efficacy test of allogenic ASCs injection

Full description

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
1. 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.
2. 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.

Enrollment

21 patients

Sex

All

Ages

19+ years old

Volunteers

No Healthy Volunteers

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