Spina BifidaIMOPUNCT03698721
Urothelium Tissue Engineering Using Biopsies From Transurethral Resection of Prostate
An observational study of Spina Bifida and Urothelial Neoplasm, run by Central Hospital, Nancy, France.
Trial summary
Different clinical conditions can require urinary bladder augmentation or replacement. Tissue engineered bladder has been clinically evaluated but is not recommended due to diverse side effects. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Spina Bifida, Urothelial Neoplasm, Bladder, Neurogenic
- What is being tested?
- Transurethral Resection of Prostate
- Type of treatment
- Surgery or procedure
- How many people
- 365 participants
- Where
- No sites listed yet
- Study dates
- Oct 2018to Oct 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Study population: Male patient requiring TURP for Benign Prostatic Hyperplasia with prostate weight evaluated preoperatively greater than or equal to 30 grams
Who may be able to join
- Patient needing a Transurethral Resection of Prostate (TURP)
- Weight of prostate (evaluated by ultrasonography)greater than or equal to 30 grams
- Affiliation to a social security system
- Patient over the age of majority
- Patient receiving complete information on research organization without opposition to the use of biological specimen
Who cannot join
- Patient for whom no TURP is realized during endoscopic procedure
- Patient for whom no resection is realized on the bladder neck
- Patient with prostate weight estimated under 30 grams
- Patient who opposed to the realization of the study
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Urothelium Tissue Engineering Using Bladder Mucosa From Transurethral Resection of Prostate
Different clinical conditions can require urinary bladder augmentation or replacement. Tissue engineered bladder has been clinically evaluated but is not recommended due to diverse side effects. Thus, there is a real interest for the development of regenerative approach with innovative scaffolds and cell transplantation.
The investigators propose the use of urothelial cells obtained by Trans-Urethral Resection of Prostate or bladder (TURP) to obtain a tissue engineered urothelium in association with different scaffolds.
Read the detailed description
Bladder biopsies will be obtained during cystoscopy, conserved in culture medium (DMEM®), digested by dispase and sowed on collagen-coated culture support. Keratinocyte Serum Free Medium (KSFM) will be used for proliferation. Microscopy, immunohistochemistry, RNA extraction, Reverse Transcription and quantitative Polymerase Chain Reaction (RT-qPCR) will be performed during passages. Cell culture conditions will be optimized to improve proliferation and avoid loss of differentiation. The investigators will develop scaffolds based on sodium alginate hydrogels, followed by freeze-drying to generate porous sponges (at -20°C and -80°C). Cultured cells will be associated to these original scaffolds and to other scaffolds, for example alginate hydrogels or Collagen Cell Carrier (CCC), cultivated for 28 days and analyzed. Histological and immunohistological appearance of cellularized scaffolds will be compared to assess the effectiveness of each scaffold for tissue engineering in urothelium.
Cellularized scaffolds will be studied in vitro (Transepithelial Electrical Resistance, impermeability, ability to be stitched, resistance to urine) and in vivo in ectopic location (subcutaneous location in Nude mice) or in orthotopic location (bladder augmentation in small animal).
- Being tested
- Transurethral Resection of Prostate
- Keywords
- Tissue engineering, Collagen scaffold, Alginate scaffold, Urothelial cells
- Medical subject headings
- Spinal Dysraphism, Urinary Bladder, Neurogenic, Bladder Exstrophy, Hypospadias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transurethral Resection of ProstateProcedure or surgery
Also called TURP, TURPs, TUPR
Transurethral resection of the prostate is a urological operation used to treat benign prostatic hyperplasia (BPH). It is performed by visualising the prostate through the urethra and removing tissue by electrocautery or sharp dissection with a resectoscope. This is considered the most effective treatment for BPH. This procedure is done with spinal or general anaesthetic. A triple lumen catheter is inserted through the urethra to irrigate and drain the bladder after the surgical procedure is complete. Outcome is considered excellent for 80-90% of BPH patients.
What is being measured
The primary outcome is the main question the study is designed to answer.
Histological analysis of biopsy.
Histological analysis with standard coloration will assess the viability of urothelium. Signs of necrosis (ulcerations, destructions of urothelium structure) will be noted.
Measured: 6 month
Secondary outcomes (16)
Immunohistological analysis of biopsy.
Immunohistological analysis using specific antibodies will locate the urothelium (Keratin, Uroplakin), the smooth muscle (Smooth muscle actin), the prostatic gland (Prostatic specific antigen).
Measured: 6 month
RT-qPCR analysis of biopsy.
RT-qPCR analysis will measure the level of expression (compared to housekeeping gene RPLP0) of RNA specific to urothelium (Keratin, Uroplakin), the smooth muscle (Smooth muscle actin), the prostatic gland (Prostatic specific antigen). This level will be compared to cultured urothelial cells.
Measured: 6 month
Digestion of the biopsy and culture with adapted medium. Optimization of culture conditions.
The biopsy will be digested using dispase. Cells will be sowed on collagen coated supports and cultured using Keratinocyte Serum Free Medium (KSFM). Trypsination will be done at confluence.
RT-qPCR (level of expression of each specific marker) will be realized at each passage to assess evolution during culture.
Measured: 12 months
Histological analysis of the cultured cells.
Cultured cells (Outcome 4) will be analyzed in contrast phase microscopy and with standard microscopy coloration to assess their morphology, the number of cellular types and their evolution throughout passages.
Measured: 12 months
Immunocytological analysis of the cultured cells.
Cultured cells (Outcome 4) will be analyzed in immunocytology to assess the type of cells (urothelial / smooth muscle / prostatic), the expression and the localization of specific markers (Outcome 2)
Measured: 12 months
RT-qPCR analysis of the cultured cells.
Cultured cells (Outcome 4) will be analyzed in RT-qPCR at each passage to assess evolution during culture. The level of expression (compared to housekeeping gene RPLP0) of RNA specific to urothelium (Keratin, Uroplakin), the smooth muscle (Smooth muscle actin), the prostatic gland (Prostatic specific antigen) will be measured.
Measured: 12 months
Development of original alginate freezed-dried scaffold
Development of an original scaffold based on sodium alginate hydrogels, followed by freeze-drying to generate porous sponges (at -20°C and -80°C).
Analysis of structure, impermeability, ability to be stitched..
Measured: 12 months
Association of the cultured cells with different scaffolds. Culture of cellularized scaffolds.
Previously cultured and analyzed cells will be associated to different scaffolds.
- Collagen scaffolds
- Alginate scaffolds
- Alginate hydrogels obtained by spray
- Original alginate freezed-dried scaffold (Outcome 4) Cellularized scaffolds will be cultured at least 28 days using previously described conditions.
Measured: 36 months
Histological analysis of cellularized scaffolds
After association, cellularized scaffolds (Outcome 9) will be cultured at least 28 days.
Survival rate using MTT assay will be performed. Histological analysis using standard colorations will be performed to evaluate the appearance of the cellularized scaffold, the location, the appearance and the organization of the cells.
Measured: 36 months
Immunohistological analysis of cellularized scaffolds
After association, cellularized scaffolds (Outcome 9) will be cultured at least 28 days.
Immunohistological analysis will be performed to evaluate the expression and location of specific markers (Outcome 2)
Measured: 36 months
RT-qPCR analysis of cellularized scaffolds
After association, cellularized scaffolds (Outcome 9) will be cultured at least 28 days.
RT-qPCR will be performed to assess evolution during culture in 3 dimensional conditions. The level of expression (compared to housekeeping gene RPLP0) of RNA specific to urothelium (Keratin, Uroplakin), the smooth muscle (Smooth muscle actin), the prostatic gland (Prostatic specific antigen) will be measured.
Measured: 36 months
Biophysical analysis of cellularized scaffolds
After association, cellularized scaffolds (Outcome 9) will be cultured at least 28 days.
Biophysical analysis on cellularized scaffolds will be done:
- Transepithelial Electrical Resistance (cellular ability to form an impermeable barrier)
- Impermeability (ability of the cellularized scaffold to form a water resistant barrier)
- Ability to be stitched (ability of the cellularized scaffold to be manipulated and stitched)
- Resistance to urine (ability of the cellularized scaffold to resist to chemical aggression of urine)
Measured: 36 months
Implantation of the cellularized scaffold in Nude mice
Cellularized scaffolds will be implanted in subcutaneous location in Nude mice. Incubation in vivo will be done during at least 28 days. Analysis (histology, immunohistology, RT-qPCR) will be performed after 28 days of incubation to assess the survival of cells and the behavior of the cellularized scaffold in vivo. Signs of necrosis, neoangiogenesis and inflammation will be noted.
Measured: 12 months
Histological analysis of implanted scaffolds
Histological analysis will be performed after 28 days of incubation on implanted scaffolds (Outcome 14) to evaluate the appearance of the cellularized scaffold, the location, the appearance and the organization of the cells.
Survival rate using MTT assay will be performed. Signs of fibrosis will be noted.
Measured: 12 months
Immunohistological analysis of implanted scaffolds
Histological analysis will be performed after 28 days of incubation on implanted scaffolds (Outcome 14) to evaluate Immunohistological analysis will be performed to evaluate the expression and location of specific markers (Outcome 2)
Measured: 12 months
RT-qPCR analysis of implanted scaffolds
RT-qPCR analysis will be performed after 28 days of incubation on implanted scaffolds (Outcome 14) to assess evolution during in vivo conditions. The level of expression (compared to housekeeping gene RPLP0) of RNA specific to urothelium (Keratin, Uroplakin), the smooth muscle (Smooth muscle actin), the prostatic gland (Prostatic specific antigen) will be measured.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2018
- Study startOct 2018 (estimated)
- Primary completionOct 2024 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Spina BifidaStudies of the same condition, open and under way.
- More trials run by Central Hospital, Nancy, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 365 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03698721
- Sponsor's protocol ID
- PSS2017/IMOPU-BERTE/MS
- Acronym
- IMOPU
- Status last verified
- Sep 2018
- First submitted
- 17 Sep 2018
- Last updated
- 9 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual data are not necessary for this study
Publications
Adamowicz J, Kowalczyk T, Drewa T. Tissue engineering of urinary bladder - current state of art and future perspectives. Cent European J Urol. 2013;66(2):202-6. doi: 10.5173/ceju.2013.02.art23. Epub 2013 Aug 13.
PubMed 24579029Lam Van Ba O, Aharony S, Loutochin O, Corcos J. Bladder tissue engineering: a literature review. Adv Drug Deliv Rev. 2015 Mar;82-83:31-7. doi: 10.1016/j.addr.2014.11.013. Epub 2014 Nov 14.
PubMed 25446136Garthwaite M, Hinley J, Cross W, Warwick RM, Ambrose A, Hardaker H, Eardley I, Southgate J. Use of donor bladder tissues for in vitro research. BJU Int. 2014 Jan;113(1):160-6. doi: 10.1111/bju.12285.
PubMed 24053725Baker SC, Shabir S, Southgate J. Biomimetic urothelial tissue models for the in vitro evaluation of barrier physiology and bladder drug efficacy. Mol Pharm. 2014 Jul 7;11(7):1964-70. doi: 10.1021/mp500065m. Epub 2014 Apr 17.
PubMed 24697150
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Urothelium Tissue Engineering Using Bladder Mucosa From Transurethral Resection of Prostate
- ClinicalTrials.gov ID
- NCT03698721
- Acronym / sponsor ID
- IMOPU / PSS2017/IMOPU-BERTE/MS
- Keywords
- Tissue engineering, Collagen scaffold, Alginate scaffold, Urothelial cells
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 365 participants (estimated)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Study start
- Oct 2018 (estimated)
- Primary completion
- Oct 2024 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 9 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Different clinical conditions can require urinary bladder augmentation or replacement. Tissue engineered bladder has been clinically evaluated but is not recommended due to diverse side effects. Thus, there is a real interest for the development of regenerative approach with innovative scaffolds and cell transplantation.
The investigators propose the use of urothelial cells obtained by Trans-Urethral Resection of Prostate or bladder (TURP) to obtain a tissue engineered urothelium in association with different scaffolds.
Detailed description
Bladder biopsies will be obtained during cystoscopy, conserved in culture medium (DMEM®), digested by dispase and sowed on collagen-coated culture support. Keratinocyte Serum Free Medium (KSFM) will be used for proliferation. Microscopy, immunohistochemistry, RNA extraction, Reverse Transcription and quantitative Polymerase Chain Reaction (RT-qPCR) will be performed during passages. Cell culture conditions will be optimized to improve proliferation and avoid loss of differentiation. The investigators will develop scaffolds based on sodium alginate hydrogels, followed by freeze-drying to generate porous sponges (at -20°C and -80°C). Cultured cells will be associated to these original scaffolds and to other scaffolds, for example alginate hydrogels or Collagen Cell Carrier (CCC), cultivated for 28 days and analyzed. Histological and immunohistological appearance of cellularized scaffolds will be compared to assess the effectiveness of each scaffold for tissue engineering in urothelium.
Cellularized scaffolds will be studied in vitro (Transepithelial Electrical Resistance, impermeability, ability to be stitched, resistance to urine) and in vivo in ectopic location (subcutaneous location in Nude mice) or in orthotopic location (bladder augmentation in small animal).
Study design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Male patient requiring TURP for Benign Prostatic Hyperplasia with prostate weight evaluated preoperatively greater than or equal to 30 grams
Key inclusion criteria (5 listed)
- Patient needing a Transurethral Resection of Prostate (TURP)
- Weight of prostate (evaluated by ultrasonography)greater than or equal to 30 grams
- Affiliation to a social security system
- Patient over the age of majority
- Patient receiving complete information on research organization without opposition to the use of biological specimen
Key exclusion criteria (4 listed)
- Patient for whom no TURP is realized during endoscopic procedure
- Patient for whom no resection is realized on the bladder neck
- Patient with prostate weight estimated under 30 grams
- Patient who opposed to the realization of the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transurethral Resection of ProstateAlso: TURP, TURPs, TUPRTransurethral resection of the prostate is a urological operation used to treat benign prostatic hyperplasia (BPH). It is performed by visualising the prostate through the urethra and removing tissue by electrocautery or sharp dissection with a resectoscope. This is considered the most effective treatment for BPH. This procedure is done with spinal or general anaesthetic. A triple lumen catheter is inserted through the urethra to irrigate and drain the bladder after the surgical procedure is complete. Outcome is considered excellent for 80-90% of BPH patients. | Procedure or surgery | – |
Primary outcome
Histological analysis of biopsy.
Time frame: 6 month
Histological analysis with standard coloration will assess the viability of urothelium. Signs of necrosis (ulcerations, destructions of urothelium structure) will be noted.
16 secondary outcomes
Immunohistological analysis of biopsy.
Time frame: 6 month
RT-qPCR analysis of biopsy.
Time frame: 6 month
Digestion of the biopsy and culture with adapted medium. Optimization of culture conditions.
Time frame: 12 months
Histological analysis of the cultured cells.
Time frame: 12 months
Immunocytological analysis of the cultured cells.
Time frame: 12 months
RT-qPCR analysis of the cultured cells.
Time frame: 12 months
Development of original alginate freezed-dried scaffold
Time frame: 12 months
Association of the cultured cells with different scaffolds. Culture of cellularized scaffolds.
Time frame: 36 months
Histological analysis of cellularized scaffolds
Time frame: 36 months
Immunohistological analysis of cellularized scaffolds
Time frame: 36 months
RT-qPCR analysis of cellularized scaffolds
Time frame: 36 months
Biophysical analysis of cellularized scaffolds
Time frame: 36 months
Implantation of the cellularized scaffold in Nude mice
Time frame: 12 months
Histological analysis of implanted scaffolds
Time frame: 12 months
Immunohistological analysis of implanted scaffolds
Time frame: 12 months
RT-qPCR analysis of implanted scaffolds
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2018.
- Background: PubMed 24579029Adamowicz J, Kowalczyk T, Drewa T. Tissue engineering of urinary bladder - current state of art and future perspectives. Cent European J Urol. 2013;66(2):202-6. doi: 10.5173/ceju.2013.02.art23. Epub 2013 Aug 13.
- Background: PubMed 25446136Lam Van Ba O, Aharony S, Loutochin O, Corcos J. Bladder tissue engineering: a literature review. Adv Drug Deliv Rev. 2015 Mar;82-83:31-7. doi: 10.1016/j.addr.2014.11.013. Epub 2014 Nov 14.
- Background: PubMed 24053725Garthwaite M, Hinley J, Cross W, Warwick RM, Ambrose A, Hardaker H, Eardley I, Southgate J. Use of donor bladder tissues for in vitro research. BJU Int. 2014 Jan;113(1):160-6. doi: 10.1111/bju.12285.
- Background: PubMed 24697150Baker SC, Shabir S, Southgate J. Biomimetic urothelial tissue models for the in vitro evaluation of barrier physiology and bladder drug efficacy. Mol Pharm. 2014 Jul 7;11(7):1964-70. doi: 10.1021/mp500065m. Epub 2014 Apr 17.
- Individual participant dataSharing planned: No. Individual data are not necessary for this study
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
An observational study of Spina Bifida and Urothelial Neoplasm, run by Central Hospital, Nancy, France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nicolas Berte, Dr (00333673004195, n.berte@chru-nancy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Histological analysis of biopsy. (time frame: 6 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03698721, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2018.