BioSphincter Implant for Bowel Incontinence

Overseen By Jin or Shannon clinical research coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Cellf Bio LLC

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: Anorectal disease, IBD, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 15

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with severe bowel control issues, particularly those unresponsive to standard medical or surgical treatments. The focus is on a bioengineered implant, the Bioengineered Internal Anal Sphincter, designed to manage fecal incontinence (FI) by replacing the internal anal sphincter, a muscle that controls bowel movements. Suitable participants should have experienced at least four episodes of uncontrolled bowel movements every two weeks for the past year, despite trying common treatments like fiber supplements, medications, or certain surgeries. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on anticoagulation therapy, it may need to be temporarily halted with permission from your prescribing provider for elective surgery.

What prior data suggests that the Bioengineered Internal Anal Sphincter is safe for humans?

Research shows that the bioengineered internal anal sphincter (IAS) has been tested in animals with promising results. When researchers implanted the IAS in mice and rats, the animals tolerated it well, showing no early signs of rejection or major problems. This suggests that the treatment might be safe for humans, but it remains early in the process. This trial marks the first time the IAS is being tested in humans, so researchers are still studying its safety and effectiveness in people. Participants should know that, as a Phase 1 trial, the main goal is to assess the safety of this new treatment for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional treatments for bowel incontinence, which often include lifestyle changes, medications, or surgical interventions like sphincteroplasty, the Bioengineered Internal Anal Sphincter implant offers a novel approach. This treatment is unique because it involves implanting a bioengineered sphincter that mimics the natural function of the anal sphincter, potentially restoring control more effectively. Researchers are excited about this treatment because it promises to provide a more durable and physiological solution by directly replacing the malfunctioning sphincter, which could significantly improve quality of life for patients with severe incontinence.

What evidence suggests that the BioSphincter Implant is effective for bowel incontinence?

Research has shown that bioengineered internal anal sphincters, which participants in this trial will receive, can help restore bowel control by increasing pressure in the area, crucial for preventing accidents. Early studies found that these sphincters, made from a patient's own cells, can successfully function and integrate into the body. They use a process involving a protein pathway that helps the sphincter remain firm and respond to signals controlling muscle movements. Although this method is new with limited human data, early signs suggest it could be promising for those who haven't succeeded with other treatments. ^{1 2 5 6 7}

Who Is on the Research Team?

Jaime Bohl, MD

Principal Investigator

Virginia Commonwealth University

Are You a Good Fit for This Trial?

Adults over 18 with severe passive fecal incontinence (FI) who've tried and failed all standard treatments, including dietary fiber, anti-diarrheal meds, biofeedback training, sacral nerve stimulation, and sphincteroplasty. Candidates must be able to understand the study and follow procedures. Women of childbearing age should use contraception.

Inclusion Criteria

I understand and agree to follow the study's requirements.

My vital signs are within normal ranges before surgery.

I am a man who can father children and will use effective birth control during the study.

Exclusion Criteria

Concurrent participation in any other clinical investigation during the period of this investigation

I have ongoing severe diarrhea that treatments haven't helped, causing incontinence.

I need a wheelchair or similar device to move around.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Biopsy and Implantation

Participants undergo a biopsy procedure to collect tissue samples followed by implantation surgery of the bioengineered BioSphincter(TM)

8 weeks

Inpatient hospital follow-up and outpatient clinic visits at Days 1, 3, 7, 14, 28, 42, and 56

Initial Follow-up

Participants are monitored for safety and initial efficacy of the implanted BioSphincter(TM) with assessments at predefined intervals

48 weeks

Medical visits at Weeks 12, 24, 36, and 48

Long-term Follow-up

Participants are monitored for long-term safety and efficacy of the implanted BioSphincter(TM)

36 months

Final safety assessments at the end of Years 2 and 3

What Are the Treatments Tested in This Trial?

Interventions

• Bioengineered Internal Anal Sphincter

Trial Overview The trial is testing a new treatment for bowel incontinence: an implanted Bioengineered Internal Anal Sphincter made from the patient's own cells. It's a Phase I study focused on safety over both short-term and long-term periods after implantation.

How Is the Trial Designed?

Group I: Implantation Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Cellf Bio LLC

Lead Sponsor

Trials

1

Recruited

10+

Published Research Related to This Trial

Bioengineered human internal anal sphincter (IAS) tissue constructs were successfully implanted in athymic rats, showing good tolerance and no early postoperative complications, indicating their potential safety for future applications.

The implanted constructs demonstrated healthy integration with surrounding tissue, maintained their contractile function, and responded to neuronal stimulation, suggesting they could effectively restore IAS function and help treat fecal incontinence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perianal implantation of bioengineered human internal anal sphincter constructs intrinsically innervated with human neural progenitor cells. Raghavan, S., Miyasaka, EA., Gilmont, RR., et al.[2021]

The implantation of bioengineered IAS BioSphincters in a Non-Human Primate model of passive fecal incontinence successfully restored anal resting pressure and recto-anal inhibitory reflex within one month, with effects sustained for up to 12 months.

Histological studies confirmed the safety and biocompatibility of the implants, showing no adverse effects and regeneration of healthy nerve and muscle tissue, suggesting this approach could significantly improve the quality of life for patients with fecal incontinence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BioSphincters to treat Fecal Incontinence in Nonhuman Primates. Dadhich, P., Bohl, JL., Tamburrini, R., et al.[2023]

The Acticon Neosphincter, the only FDA-certified artificial anal sphincter, shows promise as a treatment for severe fecal incontinence, addressing both physical and psychological impacts on patients.

A major challenge with artificial sphincters is maintaining long-term compatibility with surrounding tissues, which can be improved by using smart materials to enhance biomechanical integration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges faced in the clinical application of artificial anal sphincters. Wang, MH., Zhou, Y., Zhao, S., et al.[2018]

In a study involving 20 female rabbits, implantation of engineered autologous internal anal sphincter (IAS) biosphincters successfully restored fecal continence, as shown by improved anal pressure and reflexes measured through anorectal manometry over a 3-month period.

The treated rabbits demonstrated significant restoration of anal function compared to non-treated and sham groups, indicating that this approach could be a promising new treatment for fecal incontinence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Passive Fecal Incontinence in an Animal Model Using Engineered Biosphincters: A 3-Month Follow-Up Study. Bohl, JL., Zakhem, E., Bitar, KN.[2019]

Three-dimensional bioengineered constructs of the internal anal sphincter (IAS) can be successfully implanted in mice without rejection or inflammation, indicating their potential safety for future applications in humans.

The infusion of fibroblastic growth factor 2 significantly enhanced muscle viability and vascularity of the implanted constructs, suggesting that this treatment could improve outcomes for patients suffering from fecal incontinence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical implantation of a bioengineered internal anal sphincter. Hashish, M., Raghavan, S., Somara, S., et al.[2021]

In a study of 82 patients with severe fecal incontinence, the injection of silicone biomaterial (PTP) significantly improved fecal continence and quality of life, with effects lasting up to 12 months, especially in patients whose injections were guided by endoanal ultrasound.

There were no significant complications from the procedure, and the ultrasound confirmed that the silicone material remained in place without migration, indicating a safe and effective treatment option for internal anal sphincter dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Injectable silicone biomaterial for fecal incontinence caused by internal anal sphincter dysfunction is effective. Tjandra, JJ., Lim, JF., Hiscock, R., et al.[2005]

The study tested three growth factors (FGF-2, VEGF, and PDGF) in bioengineered internal anal sphincter (IAS) implants in mice, showing that all growth factors helped maintain smooth muscle phenotype and improved tissue characteristics compared to controls.

Among the growth factors, PDGF showed particularly promising results and is already approved for clinical use, making it a strong candidate for future clinical applications of bioengineered IAS implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo growth of a bioengineered internal anal sphincter: comparison of growth factors for optimization of growth and survival. Miyasaka, EA., Raghavan, S., Gilmont, RR., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05616208

Implantation of BioSphincter TM for Treatment of Severe ... This is a two-center first-in-human prospective Phase I study of the immediate and long-term safety of an implanted internal anal sphincter (IAS) bioengineered ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3129458/

Successful Implantation of Bioengineered, Intrinsically ... To restore fecal continence, the weakened pressure of the internal anal sphincter (IAS) must be increased. We bioengineered intrinsically innervated human ...

3. vcuhealth.org vcuhealth.org/news/vcu-health-leads-clinical-trial-for-new-treatment-to-help-people-with-bowel-control-problems/

VCU Health leads clinical trial for new treatment to help ... A research team at VCU Health is leading a clinical trial to assess a novel treatment for fecal incontinence or sudden loss of control over bowel movements.

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/cellf-bios-first-in-human-implantation-of-biosphincter/

Cellf Bio's first-in-human implantation of BioSphincter Cellf Bio reported implantation of its autologous bioengineered sphincter in Phase I clinical trial for patients with faecal incontinence.

5. gastrojournal.org gastrojournal.org/article/S0016-5085(09)00464-8/fulltext

Bioengineered Internal Anal Sphincter Derived From ... These data indicate that basal tone and acetylcholine-induced force generation depend on signaling through the PKC pathway in human IAS; PKC-mediated force ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3018766/

Surgical implantation of a bioengineered internal anal ... Three-dimensional bioengineered IAS rings can be successfully implanted into the subcutaneous tissue of recipient mice.

7. withpower.com withpower.com/trial/phase-1-fecal-incontinence-10-2022-65428

BioSphincter Implant for Bowel Incontinence Bioengineered human internal anal sphincter (IAS) tissue constructs were successfully implanted in athymic rats, showing good tolerance and no early ...