Engineered Urethral Tissue for Urethral Stricture

Recruiting at 1 trial location

Overseen By Mary-Clare Day, RN, BSN

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Wake Forest University Health Sciences

Must not be taking: Alpha blockers, Anticoagulants, Immunosuppressants, others

Disqualifiers: Diabetes, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 3

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase I clinical study to determine the safety and efficacy of using autologous, engineered urethral constructs for the treatment of urethral strictures in adult males. The proposed study design is a prospective non-randomized and uncontrolled single-center investigation. Autologous urothelial cells (UCs) and smooth muscle cells (SMCs), obtained from enrolled male subjects' bladder tissue samples, will be culture expanded in vitro and used to seed tubular PGA scaffolds to create autologous urethral constructs for the repair of urethral strictures.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive agents or certain treatments for urological conditions, you may not be eligible to participate.

What data supports the effectiveness of the treatment Autologous Engineered Urethral Construct for urethral stricture?

Research shows that using a patient's own cells to create engineered urethral tissue can help manage long and complex urethral strictures, potentially preventing them from coming back. This approach has been tested in patients needing urethral reconstruction and has shown promise in repairing urethral defects. ^{1 2 3 4 5}

Is the engineered urethral tissue treatment safe for humans?

The safety of engineered urethral tissue treatments has been studied, and they are considered promising for managing urethral strictures. These treatments use the patient's own cells, which may reduce the risk of rejection and complications, suggesting they are generally safe for human use. ^{1 2 3 4 6}

How is the treatment Autologous Engineered Urethral Construct different from other treatments for urethral stricture?

This treatment uses the patient's own cells to create a new urethral tissue, which can help prevent the recurrence of strictures (narrowing of the urethra) and offers a more natural and potentially longer-lasting solution compared to traditional surgical methods that often involve grafts or flaps. ^{1 2 3 7 8}

Research Team

James Yoo, MD

Principal Investigator

Wake Forest Institute for Regenerative Medicine

Eligibility Criteria

Adult males with urethral strictures who have had at least one failed conservative treatment, a stricture length of 10-60 mm, and can't pass a cystoscope. Excluded are those with certain skin conditions, bleeding or coagulation disorders, low albumin levels, neurological issues like MS or Parkinson's disease, untreated UTIs, systemic diseases like HIV or diabetes, recent other trial participation or investigational drug use within 30 days.

Inclusion Criteria

Patients must be available for all follow-up visits

I have a narrow area in my body that a small medical scope cannot pass through without causing damage.

I have a urethral blockage between 10-60 mm long.

Exclusion Criteria

Inability or unwillingness to sign informed consent

I do not have a bleeding disorder with low platelets or need regular blood products.

I do not have any ongoing urinary or prostate issues that would need treatment during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Biopsy and Cell Expansion

Participants undergo a full-thickness bladder biopsy to obtain urothelial and smooth muscle cells, which are then cultured and expanded over 4-6 weeks.

4-6 weeks

1 visit (in-person) for biopsy

Surgical Implantation

Participants undergo surgical removal of the urethral stricture and implantation of the autologous engineered urethral construct.

1 week

1 visit (in-person) for surgery

Follow-up

Participants are monitored for safety and effectiveness of the urethral construct, including improvement in peak urinary flow rate and adverse events.

36 months

Regular follow-up visits (in-person)

Treatment Details

Interventions

• Autologous Engineered Urethral Construct

Trial Overview The study is testing the safety and effectiveness of autologous engineered urethral constructs in men. It involves taking cells from the patient's bladder to create a tissue-engineered tube for repairing urethral strictures. This Phase I trial is non-randomized and uncontrolled at a single center.

Participant Groups

Group I: Autologous Engineered Urethral Construct Experimental Treatment 1 Intervention

All subjects enrolled will undergo a full-thickness bladder biopsy as an out-patient surgical procedure. Urothelial and Smooth Muscle Cells recovered from the biopsy will be isolated and expanded over the next 4-6 weeks, and then seeded onto a tubular scaffold to create the autologous engineered urethral construct. Subjects will undergo a second surgical procedure to excise the urethral stricture and implant the urethral construct. All subjects will be followed for 3 years for safety and efficacy.

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

Autologous engineered urethral constructs show promise as a treatment for long and complex urethral strictures, potentially offering a definitive solution.

This approach may help eliminate the recurrence of strictures, which is a common issue with traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Feasibility Study of Autologous Engineered Urethral Constructs for the Treatment of Strictures: Clinical Trial Update. Ghaffar, U., Terlecki, R., Yoo, JJ., et al.[2023]

Tissue-engineered urethras created from patients' own cells have been shown to be effective for urethral reconstruction, remaining functional for up to 6 years in a study involving 5 boys with urethral defects.

The engineered urethras maintained normal architecture and wide calibers without strictures, indicating promising long-term outcomes for patients needing complex urethral repairs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue-engineered autologous urethras for patients who need reconstruction: an observational study. Raya-Rivera, A., Esquiliano, DR., Yoo, JJ., et al.[2022]

The study successfully engineered cartilage stents using chondrocytes and polymer scaffolds, demonstrating their potential for treating urethral or ureteral stricture disease.

Both in vitro and in vivo tests showed that these stents exhibited desirable properties, such as elasticity and the ability to withstand pressure, along with confirmed cartilage formation and collagen deposition, indicating their biocompatibility and mechanical durability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue engineered stents created from chondrocytes. Amiel, GE., Yoo, JJ., Kim, BS., et al.[2019]

Autologous urine-derived stem cells (USCs) can effectively differentiate into urothelial cells and smooth muscle cells, showing promise for urethral reconstruction in a rabbit model.

Using USC-seeded small intestinal submucosa (SIS) significantly improved urethral healing, with better regeneration and less inflammation compared to SIS alone, indicating a potential new approach for treating complicated urethral strictures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urethral reconstruction with autologous urine-derived stem cells seeded in three-dimensional porous small intestinal submucosa in a rabbit model. Liu, Y., Ma, W., Liu, B., et al.[2018]

Tissue engineering for urethral reconstruction shows potential but is currently not effective for most cases of urethral stricture, with existing methods like urethrotomy yielding only 20% long-term success rates for certain patients.

While tissue-engineered substitutes for autologous oral mucosa have been used, they are expensive and require further development, as current alternatives have not produced satisfactory results in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue engineering of the urethra: where are we in 2019? Chapple, C.[2021]

Tissue-engineered grafts created from a patient's own cells and a biocompatible matrix offer a safer alternative to traditional surgery using autologous grafts for treating urethral stricture.

The article reviews the latest advancements in lab-created grafts for urethroplasty, discussing the necessary components and evaluating the pros and cons of different cellular and matrix choices based on clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Urethra Reconstruction with Tissue-Engineering Technology]. Vasyutin, IA., Lyundup, AV., Viranov, AZ., et al.[2022]

Surgical correction of urethral strictures through substitution urethroplasty is complex and often leads to complications like restenosis, impacting patients' quality of life.

Tissue engineering, utilizing various cell types and scaffolds, has shown potential in developing therapies for urethral replacement, but these methods have not yet become standard practice despite their promising clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regenerative and engineered options for urethroplasty. Pederzoli, F., Joice, G., Salonia, A., et al.[2022]

Urethroplasty is the most effective treatment for urethral strictures and anomalies, with two main types: anastomotic urethroplasty and substitution urethroplasty, the latter of which currently lacks an ideal material.

Research into bioengineered urethral tissue, including acellular and recellularized constructs, is crucial for improving urethral reconstruction techniques, as highlighted by studies in both animal and human models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential role of tissue-engineered urethral substitution: clinical and preclinical studies. Atala, A., Danilevskiy, M., Lyundup, A., et al.[2022]

References

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

Safety and Feasibility Study of Autologous Engineered Urethral Constructs for the Treatment of Strictures: Clinical Trial Update. [2023]

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

Tissue-engineered autologous urethras for patients who need reconstruction: an observational study. [2022]

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

Tissue engineered stents created from chondrocytes. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Urethral reconstruction with autologous urine-derived stem cells seeded in three-dimensional porous small intestinal submucosa in a rabbit model. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

Tissue engineering of the urethra: where are we in 2019? [2021]

6. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Urethra Reconstruction with Tissue-Engineering Technology]. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Regenerative and engineered options for urethroplasty. [2022]

8. England pubmed.ncbi.nlm.nih.gov

The potential role of tissue-engineered urethral substitution: clinical and preclinical studies. [2022]