Muscle Fiber Fragment Injections for Bowel Incontinence

Overseen By Mary-Clare Day, RN, BSN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Wake Forest University Health Sciences

Must not be taking: Immunosuppressants

Disqualifiers: Anorectal disease, Inflammatory bowel, Neurologic disease, Unstable cardiac, Uncontrolled diabetes, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to regenerate damaged anal sphincter muscles using small pieces of muscle that contain special cells. These pieces are injected into the damaged area to grow new muscle and restore function by connecting with the body's blood vessels and nerves.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you require immunosuppression or have certain health conditions, you may not be eligible to participate.

Is Muscle Fiber Fragment Injection safe for humans?

Studies on similar treatments, like autologous muscle-derived cell injections for urinary and fecal incontinence, show no serious side effects, suggesting it is generally safe for humans. ^{1 2 3 4 5}

How is the treatment of Autologous Muscle Fiber Fragment Injections for bowel incontinence different from other treatments?

This treatment is unique because it involves injecting a patient's own muscle fibers into the anal sphincter to help repair and strengthen it, which is different from traditional treatments that may not use the body's own cells. This approach aims to improve muscle function and continence by promoting muscle regeneration directly at the site of damage. ^{1 2 6 7 8}

What data supports the effectiveness of the treatment Autologous Muscle Fiber Fragment Injections for Bowel Incontinence?

Research shows that injecting muscle-derived cells into the anal sphincter has improved bowel control in patients with fecal incontinence. Similar treatments using muscle cells have also shown promise in improving urinary incontinence by increasing muscle function. ^{1 2 4 6 8}

Who Is on the Research Team?

Catherine Matthews, MD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for adults with bowel incontinence lasting over a year, who've tried other treatments without success. They must have an anal sphincter defect and frequent incontinence episodes. Women should use birth control during the study. Excluded are those with bleeding disorders, rectal pain or diseases, recent cancer, certain infections like HIV/Hepatitis B/C, severe heart/lung/kidney conditions, uncontrolled diabetes, or recent childbirth.

Inclusion Criteria

My anal sphincter has a defect of at least 30 degrees confirmed by ultrasound.

Women of childbearing potential must use acceptable contraceptives during this study

Participants must score >10 on Cleveland Clinic Fecal Incontinence Severity Scoring System (CCIS)

Exclusion Criteria

I have anemia, or my liver enzymes or bilirubin levels are higher than normal.

I do not have severe heart, lung, kidney problems, or uncontrolled diabetes.

I have had injections to bulk up my internal anal sphincter.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive autologous muscle fiber fragment injections for the treatment of fecal incontinence

12 weeks

1 visit (in-person) for injection

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

3 visits (in-person) at months 3, 6, and 12

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Muscle Fiber Fragment Injections

Trial Overview The trial tests injections of Muscle Fiber Fragments (MFF) containing muscle precursor cells to repair the anal sphincter muscle and improve bowel control. Participants will receive these injections directly into their anal sphincter to see if it can regenerate functional muscle tissue.

How Is the Trial Designed?

Group I: Muscle Fiber Fragment (MFF) injections Experimental Treatment 1 Intervention

autologous muscle fiber fragment injections, harvested in an autologous fashion from the quadriceps muscle, for the treatment of Fecal Incontinence (FI) symptoms in men and women with a demonstrated anal sphincter defect and who have failed conservative treatments

Autologous Muscle Fiber Fragment Injections is already approved in United States, European Union for the following indications:

Approved in United States as Autologous Muscle Fiber Fragments for:

• Urinary incontinence due to sphincter insufficiency
• Anal sphincter muscle regeneration

Approved in European Union as Autologous Muscle Fiber Fragments for:

• Urinary incontinence due to sphincter insufficiency

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Published Research Related to This Trial

A multicenter, placebo-controlled study showed that injecting high doses of autologous skeletal muscle-derived cells significantly improved fecal incontinence (FI) symptoms, particularly in patients with a shorter duration of FI and higher baseline incontinence episode frequency.

The treatment was safe, with no unexpected adverse events reported, and the benefits were sustained or increased over 12 months in the high cell count group, suggesting potential for this therapy in managing FI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skeletal Muscle-Derived Cell Implantation for the Treatment of Fecal Incontinence: A Randomized, Placebo-Controlled Study. Frudinger, A., Gauruder-Burmester, A., Graf, W., et al.[2023]

In a phase I clinical trial involving 10 patients with intrinsic sphincter deficiency (ISD), periurethral implantation of myofibres containing muscle precursor cells (MPCs) significantly increased intraurethral pressure and improved continence, with four out of five women experiencing notable improvements over 12 months.

The procedure was found to be safe, with no serious side effects reported, indicating that myofibre implantation could be a promising one-step treatment for urinary incontinence due to ISD, although further research is needed to enhance its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Periurethral skeletal myofibre implantation in patients with urinary incontinence and intrinsic sphincter deficiency: a phase I clinical trial. Yiou, R., Hogrel, JY., Loche, CM., et al.[2015]

In a phase 2 randomized controlled trial involving 24 patients, intrasphincteric injections of autologous myoblasts (AMs) demonstrated significant clinical benefits for fecal incontinence (FI) at 12 months, with a median Cleveland Clinic Incontinence (CCI) score improving from 15 to 6.5 (P = 0.006).

While both the AM and placebo groups showed improvement at 6 months, the AM group maintained significant benefits at 12 months, with a response rate of 58% compared to only 8% in the placebo group, indicating the potential long-term efficacy of AM therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Myoblasts for the Treatment of Fecal Incontinence: Results of a Phase 2 Randomized Placebo-controlled Study (MIAS). Boyer, O., Bridoux, V., Giverne, C., et al.[2019]

Injecting rat myoblasts into the intact anal sphincter is feasible, showing that these cells can survive and integrate into the host tissue, which could be a potential treatment for anal incontinence.

In this pilot study involving nonpregnant female Sprague Dawley rats, GFP-labeled myoblasts were successfully transplanted and confirmed to be present in the anal sphincter 10 days post-injection, indicating successful cell integration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogenic myoblast transplantation in the rat anal sphincter. Craig, JB., Lane, FL., Nistor, G., et al.[2012]

In a clinical trial involving 39 patients (average age 60.6 years), ultrasound-guided injection of autologous skeletal muscle-derived cells (SMDC) into the external anal sphincter significantly reduced weekly incontinence episodes by at least 50% in 80.6% of males and 78.4% of females after 12 months.

The procedure was well tolerated with no serious adverse events reported, suggesting it is a safe and effective treatment for fecal incontinence due to external anal sphincter damage or atrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skeletal muscle-derived cell implantation for the treatment of sphincter-related faecal incontinence. Frudinger, A., Marksteiner, R., Pfeifer, J., et al.[2019]

In a study involving 80 women with stress urinary incontinence, autologous muscle-derived cells for urinary sphincter repair showed no adverse events, indicating a strong safety profile over 12 months.

The treatment demonstrated potential efficacy, with higher doses leading to greater improvements in urinary leakage and quality of life scores, suggesting a dose-response relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous muscle derived cells for treatment of stress urinary incontinence in women. Peters, KM., Dmochowski, RR., Carr, LK., et al.[2017]

Intraurethral injection of minced autologous skeletal muscle tissue is a safe and moderately effective treatment for stress urinary incontinence, with significant reductions in leakage and improved ICIQ-SF scores observed in both uncomplicated (25% cure rate) and complicated (7% cure rate) cases after 1 year.

This simpler procedure shows comparable efficacy to more complex regenerative therapies using expanded muscle-derived cells, with no development of voiding dysfunction and only minor adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraurethral injection of autologous minced skeletal muscle: a simple surgical treatment for stress urinary incontinence. Gräs, S., Klarskov, N., Lose, G.[2014]

In a study involving 42 patients with urinary stress incontinence, transurethral ultrasound-guided injections of autologous myoblasts and fibroblasts led to complete cure in 35 patients, demonstrating the efficacy of this new treatment approach.

No postoperative side effects or complications were reported, indicating a high safety profile for this innovative therapy using autologous stem cells to treat urinary incontinence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stem cell therapy for urinary incontinence]. Strasser, H., Marksteiner, R., Margreiter, E., et al.[2018]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Skeletal Muscle-Derived Cell Implantation for the Treatment of Fecal Incontinence: A Randomized, Placebo-Controlled Study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Periurethral skeletal myofibre implantation in patients with urinary incontinence and intrinsic sphincter deficiency: a phase I clinical trial. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Autologous Myoblasts for the Treatment of Fecal Incontinence: Results of a Phase 2 Randomized Placebo-controlled Study (MIAS). [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Allogenic myoblast transplantation in the rat anal sphincter. [2012]

5. England pubmed.ncbi.nlm.nih.gov

Skeletal muscle-derived cell implantation for the treatment of sphincter-related faecal incontinence. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Autologous muscle derived cells for treatment of stress urinary incontinence in women. [2017]

7. United States pubmed.ncbi.nlm.nih.gov

Intraurethral injection of autologous minced skeletal muscle: a simple surgical treatment for stress urinary incontinence. [2014]

8. Germany pubmed.ncbi.nlm.nih.gov

[Stem cell therapy for urinary incontinence]. [2018]