Clinical trial NCT02384499: 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
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Fecal Incontinence
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2015-03-10
Enrollment: 21
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: * 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinically measured abnormality of laboratory tests and adverse events
timeFrame: one year (12 months)
Secondary outcomes:
measure: Satisfaction as measured by Wexner Score
timeFrame: one year (12 months)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Section of Colon and Rectal Surger, Department of Surgery, Yonsei University College of Medicine
Study officials:
References:
citation: White AB, Keller PW, Acevedo JF, Word RA, Wai CY. Effect of myogenic stem cells on contractile properties of the repaired and unrepaired transected external anal sphincter in an animal model. Obstet Gynecol. 2010 Apr;115(4):815-823. doi: 10.1097/AOG.0b013e3181d56cc5.
citation: Parmar N, Kumar L, Emmanuel A, Day RM. Prospective regenerative medicine therapies for obstetric trauma-induced fecal incontinence. Regen Med. 2014;9(6):831-40. doi: 10.2217/rme.14.56.
citation: Kang SB, Lee HN, Lee JY, Park JS, Lee HS, Lee JY. Sphincter contractility after muscle-derived stem cells autograft into the cryoinjured anal sphincters of rats. Dis Colon Rectum. 2008 Sep;51(9):1367-73. doi: 10.1007/s10350-008-9360-y. Epub 2008 Jun 7.
citation: Lorenzi B, Pessina F, Lorenzoni P, Urbani S, Vernillo R, Sgaragli G, Gerli R, Mazzanti B, Bosi A, Saccardi R, Lorenzi M. Treatment of experimental injury of anal sphincters with primary surgical repair and injection of bone marrow-derived mesenchymal stem cells. Dis Colon Rectum. 2008 Apr;51(4):411-20. doi: 10.1007/s10350-007-9153-8. Epub 2008 Jan 26.
citation: Garcia-Olmo D, Herreros D, Pascual I, Pascual JA, Del-Valle E, Zorrilla J, De-La-Quintana P, Garcia-Arranz M, Pascual M. Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Dis Colon Rectum. 2009 Jan;52(1):79-86. doi: 10.1007/DCR.0b013e3181973487.
citation: Rockwood TH, Church JM, Fleshman JW, Kane RL, Mavrantonis C, Thorson AG, Wexner SD, Bliss D, Lowry AC. Fecal Incontinence Quality of Life Scale: quality of life instrument for patients with fecal incontinence. Dis Colon Rectum. 2000 Jan;43(1):9-16; discussion 16-7. doi: 10.1007/BF02237236.
citation: Park EJ, Kang J, Baik SH. Treatment of faecal incontinence using allogeneic-adipose-derived mesenchymal stem cells: a study protocol for a pilot randomised controlled trial. BMJ Open. 2016 Feb 17;6(2):e010450. doi: 10.1136/bmjopen-2015-010450.