Cell-Based Therapy for Stress Urinary Incontinence

(CELLEBRATE Trial)

Recruiting at21 trial locations

Overseen by Melissa Kaufman, M.D., Ph.D.

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: Cook MyoSite

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for women who still have urine leakage after surgery. The treatment uses their own muscle cells, which are injected into the urinary passage to help strengthen it. The goal is to reduce accidental urine leakage during activities like laughing or coughing. Muscle-derived cells have been previously used in treatments for urinary incontinence, showing promise in improving urethral closure and reducing symptoms.

Do I have to stop taking my current medications for the trial?

You may need to stop or adjust your current medications if they affect lower urinary tract function. If you are taking such medications, you must be on a stable dose for at least 2 weeks before the trial and maintain it during the study.

What data supports the idea that Cell-Based Therapy for Stress Urinary Incontinence is an effective treatment?

The available research shows that Cell-Based Therapy for Stress Urinary Incontinence, specifically using autologous muscle-derived cells, is effective. One study found that these cells helped repair the urinary sphincter in women with stress urinary incontinence. Another study showed that injections of these cells reduced the frequency of stress incontinence episodes. Additionally, in animal studies, this therapy improved the function of the urethral sphincter, which is important for controlling urination. Compared to other treatments, this cell-based approach directly targets the muscles involved in urinary control, potentially offering a more direct and effective solution. ^{1 2 3 4 5}

What safety data is available for cell-based therapy for stress urinary incontinence?

The safety data for cell-based therapy, specifically autologous muscle-derived cells (AMDC), for stress urinary incontinence indicates that the treatment is generally safe. Multiple studies, including double-blind, randomized, placebo-controlled trials, have been conducted to assess the safety and efficacy of AMDC. These studies report no serious procedure or treatment-related adverse events. In trials for underactive bladder, which also used AMDC, no study-related adverse events or side effects were reported, and the treatment was described as safe and minimally invasive. Overall, the existing safety data suggests that AMDC therapy is a promising and safe treatment option for urinary incontinence. ^{1 2 6 7 8}

Is the treatment AMDC-USR (iltamiocel) a promising treatment for stress urinary incontinence?

Yes, AMDC-USR (iltamiocel) is a promising treatment for stress urinary incontinence. Studies show it can help repair the urinary sphincter muscle, reduce incontinence episodes, and improve muscle function. This cell-based therapy offers hope for those who haven't found success with other treatments. ^{1 2 3 8 9}

Research Team

Melissa Kaufman, M.D., Ph.D.

Principal Investigator

Vanderbilt University Medical Center, Department of Urologic Surgery

Eligibility Criteria

This trial is for adult women over 18 who have moderate-to-severe stress urinary incontinence despite having surgery for it. They must not be pregnant, planning pregnancy, or breastfeeding, and should not have a BMI of 35 or higher. Participants need to have tried other treatments like pelvic exercises and cannot be on certain medications affecting the bladder.

Inclusion Criteria

I am a woman over 18 with severe bladder control issues for 6+ months.

Must have completed 100% of the screening 3-day diary evening reports

I have had surgery for stress urinary incontinence before.

Exclusion Criteria

My BMI is 35 or higher.

I mainly experience sudden urges to urinate that I cannot control.

I have experienced stress urinary incontinence for less than 6 months.

Treatment Details

Interventions

• AMDC-USR (iltamiocel) (Cell Therapy)
• Placebo (Other)

Trial Overview The study tests Autologous Muscle Derived Cells (AMDC-USR) against a placebo in reducing stress incontinence episodes. Women will randomly receive either cell injections or a placebo to see which is more effective at treating their condition after previous surgeries failed.

Participant Groups

Group I: AMDC-USR (iltamiocel) Experimental Treatment 1 Intervention

Autologous muscle-derived cells for urinary sphincter repair (AMDC-USR; generic name: iltamiocel) is the study product.

Group II: Placebo Placebo Group 1 Intervention

Placebo control is the vehicle solution used for the study product.

Who Is Running the Clinical Trial?

Cook MyoSite

Lead Sponsor

Trials

14

Recruited

1,100+

Findings from Research

The study found that autologous muscle-derived cells for urinary sphincter repair (AMDC-USR) were safe and well-tolerated, with no serious adverse events reported among female subjects with stress urinary incontinence.

Although the primary efficacy results were inconclusive due to a high placebo response rate (90%), post hoc analyses indicated that stricter endpoints might reveal a potential treatment effect, suggesting the need for refined trial designs in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, placebo-controlled clinical trial evaluating the safety and efficacy of autologous muscle derived cells in female subjects with stress urinary incontinence. Jankowski, RJ., Tu, LM., Carlson, C., et al.[2021]

In a study of 58 participants, both autologous muscle-derived cell (AMDC) injections and placebo injections led to significant increases in urethral sphincter volumes and reductions in stress incontinence episode frequency (IEF) after 12 months, but there were no significant differences between the two groups.

Factors such as longer urethral length and larger external sphincter volume at baseline were associated with better responses to AMDC injections, suggesting these may be important predictors of treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the effects of autologous muscle-derived cell injections on urethral sphincter morphometry using 3D/4D ultrasound. Ismail, S., Morin, M., Tu, LM.[2021]

Skeletal muscle-derived mononuclear cells (SMDMCs) were successfully incorporated into the urethra of female rats, promoting recovery of the damaged urethral sphincter after stress urinary incontinence surgery.

The SMDMC treatment led to a significant reduction in connective tissue deposition and an increase in muscle content compared to the saline control group, indicating potential efficacy for this novel cell-based therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Periurethral muscle-derived mononuclear cell injection improves urethral sphincter restoration in rats. Turco, MP., de Souza, AB., de Campos Sousa, I., et al.[2018]

Iltamiocel, a cellular therapy using autologous muscle-derived cells, was found to be safe with no serious adverse events reported in a study of 48 adults with fecal incontinence.

At 12 months post-treatment, participants experienced a significant reduction in fecal incontinence episodes and improved quality of life, with over half of the participants showing a ≥50% reduction in episodes and nearly a quarter achieving complete continence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Iltamiocel Cellular Therapy for the Treatment of Fecal Incontinence. Results of a Phase 1/2 Study. Knowles, CH., Canestrari, E., Jankowski, RJ., 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 clinical trial involving 20 patients with underactive bladder (UAB), intradetrusor injections of Autologous Muscle Derived Cells (AMDC) showed promising safety and efficacy, with 58% of patients reporting significant improvement in symptoms at 12 months post-treatment.

No serious adverse events were reported, and improvements included reduced post-void residual urine volume and increased voiding efficiency, suggesting that AMDC therapy could be a viable option for patients with chronic urinary retention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved global response outcome after intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder. Gilleran, J., Diokno, AC., Ward, E., et al.[2021]

The first clinical trial using autologous muscle-derived stem cells (AMDC) for treating underactive bladder (UAB) showed no adverse events, indicating that the treatment is safe.

After one year, while the patient still required self-catheterization, there was a notable reduction in maximum bladder capacity, suggesting that AMDC injections may improve bladder function in UAB patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder: pilot study. Levanovich, PE., Diokno, A., Hasenau, DL., et al.[2018]

Autologous mesenchymal-derived stem cells (AMDC) have shown an 80% improvement in urinary incontinence symptoms for both men and women, indicating their efficacy as a treatment for stress urinary incontinence (SUI).

The precision of cell injection is crucial for treatment success, and using robotic-assisted systems for endoscopic procedures may enhance the effectiveness of AMDC treatments by ensuring accurate placement of the injected cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regenerative medicine- techniques and methods of administering autologous derived stem cells in urinary incontinence. Stangel-Wojcikiewicz, K., Petko, M., Kobus, K., et al.[2018]

Stress urinary incontinence affects a significant portion of the population, particularly the elderly, with around 25% of seniors experiencing this condition due to degeneration of the sphincter muscle.

Cell-based therapies using stem cells, such as mesenchymal stromal cells and urine-derived stem cells, show promise in improving sphincter muscle function when other treatments fail, and advancements in surgical techniques and evaluation methods are being developed to enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards a Treatment of Stress Urinary Incontinence: Application of Mesenchymal Stromal Cells for Regeneration of the Sphincter Muscle. Aicher, WK., Hart, ML., Stallkamp, J., et al.[2020]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, placebo-controlled clinical trial evaluating the safety and efficacy of autologous muscle derived cells in female subjects with stress urinary incontinence. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Assessment of the effects of autologous muscle-derived cell injections on urethral sphincter morphometry using 3D/4D ultrasound. [2021]

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

Periurethral muscle-derived mononuclear cell injection improves urethral sphincter restoration in rats. [2018]

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

Safety and Efficacy of Iltamiocel Cellular Therapy for the Treatment of Fecal Incontinence. Results of a Phase 1/2 Study. [2023]

5. 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]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Improved global response outcome after intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder: pilot study. [2018]

8. Poland pubmed.ncbi.nlm.nih.gov

Regenerative medicine- techniques and methods of administering autologous derived stem cells in urinary incontinence. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Towards a Treatment of Stress Urinary Incontinence: Application of Mesenchymal Stromal Cells for Regeneration of the Sphincter Muscle. [2020]