Implantation of BioSphincter TM for Treatment of Severe Passive Fecal Incontinence

NCT05616208 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is first-in-human prospective Phase I study of the immediate and long-term safety of an implanted internal anal sphincter (IAS) bioengineered from autologous cells to treat subjects with severe passive FI who have failed standard treatments.

Conditions

Fecal Incontinence

Keywords

fecal incontinence; accidental bowel leakage; fecal urgency

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events of Implanted BioSphincter IAS for patients with severe FI Who Have Failed Standard Treatment

  To determine the safety of IAS cell harvest and the implanted BioSphincter IAS in subjects with severe FI. Occurrence of adverse events. * Occurrence, severity, duration, and relationship to study procedures. * The safety of all surgical and diagnostic procedures will be assessed at inpatient hospital follow-up and outpatient clinic visits at predefined intervals. * Biopsy: Site of IAS cell harvest will be assessed postoperatively at Days 1, 7, and 21. * BioSphincter implantation will be assessed postoperatively at postoperative Days 1, 3, 7, 14, 28, 42 (week 6) and 56 (week 8). Additional safety assessments will be made at medical visits on Weeks 12, 24, 36 and 48-post implantation. Final safety assessments will be made a.t the end of Years 2 and 3

  12-36 months

Secondary Outcomes (10)

• Initial efficacy of the implanted IAS in decreasing the number of episodes of incontinence in subjects with severe FI.

  12-48 weeks

• Initial efficacy of the implanted IAS in decreasing the number of episodes of fecal urgency in subjects with severe FI.

  12-48 weeks

• Change from Baseline CCIS Score of the implanted IAS in improving quality of life

  12-48 weeks

• Change from Baseline FISI Score of the implanted IAS in improving quality of life

  12-48 weeks

• Change from Baseline FIQOL Score of the implanted IAS in improving quality of life

  12-48 weeks

Study Arms (1)

Implantation

EXPERIMENTAL

This is a non-randomized, single group treatment study with a single arm and is not subject or investigator masked or blinded. BioSphincters will be implanted in every study subject.

Biological: Bioengineered Internal Anal Sphincter

Interventions

Bioengineered Internal Anal Sphincter BIOLOGICAL

Autologous Bioengineered Internal Anal Sphincter

Also known as: BioSphincter(TM)

Implantation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are eligible to be included in the study only if all of the following criteria apply:
• Males and females aged 18 years old and over at the time of signing the IRB approved informed consent.
• Have the ability to understand the requirements of the study and are willing to comply with all study procedures.
• In the opinion of the investigator, able to participate in the study.
• Experience four or more FI episodes per 2-week period for the past 12 months. For purposes of this study, FI is defined as the loss of control sufficient to have stool in the subject's undergarments or require the changing of the undergarments. FI does not include the presence of a minimal amount of fecal material on the subject's undergarments and does not require the changing of the undergarments.
• Failed standard medical and surgical therapies for FI as defined below:
• Failure of standard medical therapy is defined as
• Bulking agents such as Citrucel or Metamucil fail to decrease the frequency of FI episodes to 4 or fewer episodes per two-week period after 4 weeks of treatment. Treatment failure is defined as a lack of response to the intervention after 4 weeks of treatment. Upon initiation of fiber, patients should see a change in stool consistency within 24-48 hours. Additional time for fiber treatment is needed to titrate the dose to optimize stool consistency and minimize side effects of bloating and increased flatus. Four weeks allows time to change stool consistency and measure changes in FI with a stable fiber regimen.
• Antidiarrheal agents such as Imodium or Lomotil may decrease FI or produce constipation but fail to decrease the frequency of FI episodes to 4 or fewer episodes per two-week period after 4 weeks of treatment. Treatment failure is defined as a lack of response to the intervention after 4 weeks of treatment. Upon initiation of Imodium or Lomotil, the patient should see a change in stool frequency within 24-48 hours. Additional time on Imodium/Lomotil treatment is needed to titrate the dose to optimize stool frequency and minimize side effects of bloating. Four weeks allows time to change stool frequency and measure changes in FI on a stable Imodium/Lomotil regimen.
• Failure of biofeedback training to reduce the frequency of FI episodes to 4 or fewer episodes per two-week period after 4 weeks of treatment. Treatment failure is defined as a lack of response to the intervention after 3 months of treatment. Three months of physical therapy is needed to allow strengthening of pelvic floor musculature and improvement in pelvic floor coordination.
• Failure of standard surgical therapy is defined as
• Sacral nerve stimulation (SNS) fails to decrease the frequency of FI episodes to 4 or fewer episodes per two-week period after 2 months or more of treatment. SNS requires a two week period for two surgeries, trial implantation and then permanent implantation. During the two week period, patients can see a change in FI symptoms secondary to SNS implantation that informs the decision to proceed with permanent implantation. After permanent implantation, the settings of the SNS can be manipulated to optimize fecal control and minimize patient side effects. Two months allows time for the two surgeries to occur and SNS setting changes to ensure optimization of FI. Failure of SNS treatment will also include patients who have SNS explantation due to complications or side effects. Finally, SNS failure will also include patients who fail test stimulation and do not undergo chronic implantation. Patients can be considered to have SNS failure if after informed consent for the procedure, they elect to not undergo SNS trial or implantation.
• Sphincteroplasty failure will have occurred if the FI episode frequency is four or more episodes per two-week period, 12 months or more after surgical repair. After sphincteroplasty, patients may initially see an improvement in FI. However, over time, there has been a measured degradation in response to this surgical despite intact sphincter repair. Therefore, after 12 months, if a patient has undergone sphincteroplasty but fails to have improvement in FI, OR redevelops FI after initial improvement in FI, the patient will be eligible for potential trial enrollment.
• Patients with severe passive fecal incontinence are eligible for the trial if they have failed all medical and surgical therapy for fecal incontinence and are being considered for a colostomy.
• Anorectal manometry (ARM) testing history of ARM while at the discretion of the Physician/Surgeon. ARM must show low IAS pressure and presence of the Recto Anal Inhibitory Reflex (RAIR). Low IAS pressure is defined as ≤ 60 mmHg during the anorectal motility exam performed with a high-resolution catheter. Normal IAS pressure range is \> 60 mm Hg.

You may not qualify if:

• Symptomatic anorectal disease including hemorrhoid disease, anal fissure, or fistula causing symptoms such as bleeding, swelling, pain, or drainage.
• Pre-existing anorectal pain of any cause.
• Incontinence of flatus only.
• Chronic watery diarrhea unmanaged by medical therapy and which is the primary cause for FI.
• Greater than 60 degrees of either external anal sphincter disruption or both (\>60° IAS and EAS). Patients with severe (\>60 degree) disruption of the EAS ± IAS are likely to have a component of both urge (EAS) and passive (IAS) fecal incontinence. Due to a combined etiology of FI, patients with a large EAS ± IAS disruption are unlikely to have a significant improvement in FI from BioSphincter treatment.
• Acute or chronic anorectal infections (including proctitis, recurrent abscesses, or fistulae).
• Presence of anorectal tumors.
• Active proctitis.
• Uncontrolled inflammatory bowel disease (IBD) characterized by one or more of the following: CRP 10 mg/L, fecal calprotectin \> 200 mg/L, new or uncontrolled symptoms of IBD, endoscopic disease, evidence of inflammation on MR Imaging.
• Any illness or disease requiring chemotherapy or any malignant disease within 5 years of enrollment.
• History of organ transplantation requiring immunosuppressive medications.
• History of a bleeding disorder diagnosed and treated by a hematologist, or patient with a diagnosed bleeding disorder currently being treated by a hematologist. If patient is on anticoagulation therapy which can be temporarily halted with permission from the prescribing provider for elective surgery, the patient will be eligible for the trial.
• History of pelvic radiation, rectal prolapse, anorectal malformations, anorectal surgery within the previous 12 months or current colostomy..
• Neurologic disease characterized by significant peripheral neuropathy or spinal cord dysfunction.
• Mobility impairment requiring the use of assistive devices (e.g., wheelchair).

Sponsors & Collaborators

• Cellf Bio LLC: lead

Study Sites (1)

Virginia Commonwealth University Health Main Hospital (VCU)

Richmond, Virginia, 23219, United States

Location

Related Publications (21)

• Baxter NN, Rothenberger DA, Lowry AC. Measuring fecal incontinence. Dis Colon Rectum. 2003 Dec;46(12):1591-605. doi: 10.1007/BF02660762.

  PMID: 14668583 BACKGROUND

• Bharucha AE, Fletcher JG, Seide B, Riederer SJ, Zinsmeister AR. Phenotypic variation in functional disorders of defecation. Gastroenterology. 2005 May;128(5):1199-210. doi: 10.1053/j.gastro.2005.03.021.

  PMID: 15887104 BACKGROUND

• Cleveland Clinic Incontinence Score. Vol. 0, 2021, p. 1993.

  BACKGROUND

• Engel AF, Kamm MA, Bartram CI, Nicholls RJ. Relationship of symptoms in faecal incontinence to specific sphincter abnormalities. Int J Colorectal Dis. 1995;10(3):152-5. doi: 10.1007/BF00298538.

  PMID: 7561433 BACKGROUND

• Farouk R, Duthie GS, Pryde A, McGregor AB, Bartolo DC. Internal anal sphincter dysfunction in neurogenic faecal incontinence. Br J Surg. 1993 Feb;80(2):259-61. doi: 10.1002/bjs.1800800250.

  PMID: 8443675 BACKGROUND

• Fecal Incontinence Quality of Life Scale (FIQOL). 2021.

  BACKGROUND

• Fecal Incontinence Severity Index ( FISI ). 2021.

  BACKGROUND

• Goode PS, Burgio KL, Halli AD, Jones RW, Richter HE, Redden DT, Baker PS, Allman RM. Prevalence and correlates of fecal incontinence in community-dwelling older adults. J Am Geriatr Soc. 2005 Apr;53(4):629-35. doi: 10.1111/j.1532-5415.2005.53211.x.

  PMID: 15817009 BACKGROUND

• Huebner M, Margulies RU, Fenner DE, Ashton-Miller JA, Bitar KN, DeLancey JO. Age effects on internal anal sphincter thickness and diameter in nulliparous females. Dis Colon Rectum. 2007 Sep;50(9):1405-11. doi: 10.1007/s10350-006-0877-7.

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• Jorge JM, Wexner SD. Etiology and management of fecal incontinence. Dis Colon Rectum. 1993 Jan;36(1):77-97. doi: 10.1007/BF02050307.

  PMID: 8416784 BACKGROUND

• Luo C, Samaranayake CB, Plank LD, Bissett IP. Systematic review on the efficacy and safety of injectable bulking agents for passive faecal incontinence. Colorectal Dis. 2010 Apr;12(4):296-303. doi: 10.1111/j.1463-1318.2009.01828.x. Epub 2009 Mar 6.

  PMID: 19320664 BACKGROUND

• Maeda Y, Laurberg S, Norton C. Perianal injectable bulking agents as treatment for faecal incontinence in adults. Cochrane Database Syst Rev. 2013 Feb 28;2013(2):CD007959. doi: 10.1002/14651858.CD007959.pub3.

  PMID: 23450581 BACKGROUND

• Norton C, Cody JD. Biofeedback and/or sphincter exercises for the treatment of faecal incontinence in adults. Cochrane Database Syst Rev. 2012 Jul 11;2012(7):CD002111. doi: 10.1002/14651858.CD002111.pub3.

  PMID: 22786479 BACKGROUND

• Omar MI, Alexander CE. Drug treatment for faecal incontinence in adults. Cochrane Database Syst Rev. 2013 Jun 11;2013(6):CD002116. doi: 10.1002/14651858.CD002116.pub2.

  PMID: 23757096 BACKGROUND

• Rao SS. Pathophysiology of adult fecal incontinence. Gastroenterology. 2004 Jan;126(1 Suppl 1):S14-22. doi: 10.1053/j.gastro.2003.10.013.

  PMID: 14978634 BACKGROUND

• 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.

  PMID: 10813117 BACKGROUND

• Sangwan YP, Coller JA, Schoetz DJ, Roberts PL, Murray JJ. Spectrum of abnormal rectoanal reflex patterns in patients with fecal incontinence. Dis Colon Rectum. 1996 Jan;39(1):59-65. doi: 10.1007/BF02048271.

  PMID: 8601359 BACKGROUND

• Tan JJ, Chan M, Tjandra JJ. Evolving therapy for fecal incontinence. Dis Colon Rectum. 2007 Nov;50(11):1950-67. doi: 10.1007/s10350-007-9009-2.

  PMID: 17874167 BACKGROUND

• Whitehead WE, Palsson OS, Simren M. Treating Fecal Incontinence: An Unmet Need in Primary Care Medicine. N C Med J. 2016 May-Jun;77(3):211-5. doi: 10.18043/ncm.77.3.211.

  PMID: 27154893 BACKGROUND

• Zbar AP, Khaikin M. Should we care about the internal anal sphincter? Dis Colon Rectum. 2012 Jan;55(1):105-8. doi: 10.1097/DCR.0b013e318235b645.

  PMID: 22156875 BACKGROUND

• Zutshi M, Tracey TH, Bast J, Halverson A, Na J. Ten-year outcome after anal sphincter repair for fecal incontinence. Dis Colon Rectum. 2009 Jun;52(6):1089-94. doi: 10.1007/DCR.0b013e3181a0a79c.

  PMID: 19581851 BACKGROUND

MeSH Terms

Conditions

Fecal Incontinence

Condition Hierarchy (Ancestors)

Rectal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• Jaime Bohl, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a non-randomized, single group treatment study with a single arm and is not subject or investigator masked or blinded.

Study Record Dates

• First Submitted: October 31, 2022
• First Posted: November 15, 2022
• Study Start: November 2, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: April 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)