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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating urethral strictures, which are narrowings of the urethra that make urination difficult. The trial uses a special treatment called Autologous Engineered Urethral Construct, made from a patient's own bladder cells, to repair these strictures. Researchers aim to determine if this new approach is safe and effective. Men with a history of urethral strictures that prevent the passage of a medical tool called a cystoscope might be suitable for this study. Participants must attend all follow-up visits and speak English. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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 prior data suggests that this engineered urethral tissue is safe for treating urethral strictures?

Research shows that using specially made urethral structures from a person’s own cells could effectively treat urethral strictures, a narrowing of the urethra. These structures have shown potential for safety and effectiveness. Earlier studies using similar tissue-engineered structures for urethral repair were generally well-tolerated, with few side effects reported. This suggests the treatment could be safe for humans. However, as this is an early-phase study, the primary goal is to better understand the safety of this approach. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the Autologous Engineered Urethral Construct because it offers a groundbreaking approach for treating urethral stricture. Unlike traditional treatments, which often involve repetitive surgeries to widen or replace the narrowed section of the urethra, this method uses a patient's own cells to engineer a new urethral segment. This personalized tissue engineering aims not only to reduce the risk of rejection but also to provide a long-term solution, potentially minimizing the need for future interventions. By creating a urethra from the patient's own cells, it also holds promise for better integration and function, which could dramatically improve the quality of life for individuals with this condition.

What evidence suggests that this autologous engineered urethral construct is effective for urethral strictures?

Research has shown that using a patient's own cells to create new urethras might help treat urethral strictures, which are narrowings in the urethra. Past studies demonstrated that these tissue-engineered urethras successfully repaired damaged urethras in patients. In this trial, participants will receive an Autologous Engineered Urethral Construct, which involves taking cells from a patient's bladder to build a new urethra, offering a personalized and natural treatment option. Other research has found that using similar methods, such as creating tissue from the lining of the mouth, is safe and has few side effects. These findings suggest that this new treatment could improve urethra function and reduce complications. ^{1 6 7 8 9}

Who Is on the Research Team?

James Yoo, MD

Principal Investigator

Wake Forest Institute for Regenerative Medicine

Are You a Good Fit for This Trial?

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.

My kidney function is impaired.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S2405456923002092

Safety and Feasibility Study of Autologous Engineered ...

This trial is investigating a promising and novel definitive treatment option for long and complex urethral strictures with the prospect of eliminating ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5605371/

Results of Use of Tissue-Engineered Autologous Oral ...

Autologous tissue-engineered oral mucosa is a safe option for urethral reconstruction, with minimal donor-site morbidity.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4005887/

Tissue-engineered autologous urethras for patients who ...

We aimed to assess the effectiveness of tissue-engineered urethras using patients' own cells in patients who needed urethral reconstruction.

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clinicaltrial.be

clinicaltrial.be/en/details/21816?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Safety and Feasibility Study of Autologous Engineered Ure...

Secondary outcomes. 1. Effectiveness of urethral construct in repairing urethral stricture. Improvement in peak urinary flow rate defined as ...

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clinicaltrials.ucsf.edu

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Autologous Engineered Urethral Constructs for the ...

This is a Phase I clinical study to determine the safety and efficacy of using autologous, engineered urethral constructs for the treatment of urethral ...

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pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37775398/

Safety and Feasibility Study of Autologous Engineered ...

Autologous engineered urethral constructs are a promising treatment option for definitive management of long and complex urethral strictures, with the prospect ...

7.

eu-focus.europeanurology.com

eu-focus.europeanurology.com/article/S2405-4569(23)00209-2/abstract

Safety and Feasibility Study of Autologous Engineered ...

While short strictures may be managed with dilation, stricture excision, or nontransecting approaches, longer strictures require grafting.

8.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/34053150/

Safety and mid-term surgical results of anterior ...

Anterior one-stage urethroplasty using MukoCell showed in our hands a mid-term success rate of up to 68.8% without significant adverse events.

9.

thelancet.com

thelancet.com/article/S2352-3964(17)30331-6/fulltext

Results of Use of Tissue-Engineered Autologous Oral ...

Autologous tissue-engineered oral mucosa is a safe option for urethral reconstruction, with minimal donor-site morbidity.