SURF is a randomised controlled, parallel group, single blind phase II study designed to assess the safety and potential efficacy of an innovative therapeutic strategy for urethral stenosis based on adjuvant injection of autologous Adipose-Derived Stromal Vascular Fraction of Adipose Tissue (ADSVF) during endoscopic urethrotomy (standard care).
Urethral stenosis (UrS) is a narrowing of the urethra's caliber. UrS results of ischemic fibrosis of the corpus spongiosum (spongiofibrosis). Fibrosis-induced retraction reduces the size of the urethral lumen. Spongiofibrosis may be due to infections, inflammation, trauma but remains mostly idiopathic.Endo-urethral treatment exposes to a high rate of recurrence (up to 60% depending on the site, length and etiology). The reconstruction treatment is more effective but more complex (use of oral mucosal flap or other substitution tissue, less mastered by the surgical community and more morbid. The (ADSVF) is an easily accessible source of autologous mesenchymal stem cells. Obtention from lipoaspirates is safe, simple and standardized. Different animal models have demonstrated the pro-healing and anti-fibrotic properties of autologous ADSVF in the urethra corpus cavernous during erectile dysfunction, perineal fistulas during Crohn's disease and systemic sclerosis. The main objective of this study is to assess the safety and tolerability of ADSVF, as add-on treatment to endoscopic urethrotomy for recurrent bulbar urethral stenosis during the follow-up.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
20
The surgeon will perform lipoaspiration under local anesthesia for the ADSVF production.
The urologist will perform an endoscopic urethrotomy (standard care).
ADSVF will be administrated in fibrotic lesion during urethrotomy by the urologist.
Assistance Publique Hopitaux de Marseille
Marseille, France
RECRUITINGBaseline intensity and duration of urethral pain
A degree of pain can be expected at the tissue sampling site. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator. The events intensity will be graded according to the version 5.0 of Common Terminology Criteria for Adverse Events (CTCAE) classification (grade 1 to 5 toxicity) of National Cancer Institute.
Time frame: 1 day
Intensity and duration of urethral pain D7
measured 7 days after therapeutic administration. A degree of pain can be expected at the tissue sampling site. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator. The events intensity will be graded according to the version 5.0 of Common Terminology Criteria for Adverse Events (CTCAE) classification (grade 1 to 5 toxicity) of National Cancer Institute.
Time frame: 7 days
Intensity and duration of urethral pain M1
measured 1 month after therapeutic administration. A degree of pain can be expected at the tissue sampling site. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator. The events intensity will be graded according to the version 5.0 of Common Terminology Criteria for Adverse Events (CTCAE) classification (grade 1 to 5 toxicity) of National Cancer Institute.
Time frame: 1 month
Intensity and duration of urethral pain M3
measured 3 months after therapeutic administration. A degree of pain can be expected at the tissue sampling site. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator. The events intensity will be graded according to the version 5.0 of Common Terminology Criteria for Adverse Events (CTCAE) classification (grade 1 to 5 toxicity) of National Cancer Institute.
Time frame: 3 months
Intensity and duration of urethral pain M6
measured 6 months after therapeutic administration. A degree of pain can be expected at the tissue sampling site. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator. The events intensity will be graded according to the version 5.0 of Common Terminology Criteria for Adverse Events (CTCAE) classification (grade 1 to 5 toxicity) of National Cancer Institute.
Time frame: 24 months
Intensity and duration of urethral pain M9
measured 9 months after therapeutic administration. A degree of pain can be expected at the tissue sampling site. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator. The events intensity will be graded according to the version 5.0 of Common Terminology Criteria for Adverse Events (CTCAE) classification (grade 1 to 5 toxicity) of National Cancer Institute.
Time frame: 9 months
Intensity and duration of urethral pain M18
measured 18 months after therapeutic administration. A degree of pain can be expected at the tissue sampling site. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator. The events intensity will be graded according to the version 5.0 of Common Terminology Criteria for Adverse Events (CTCAE) classification (grade 1 to 5 toxicity) of National Cancer Institute.
Time frame: 18 months
Intensity and duration of urethral pain M24
measured 24 months after therapeutic administration. A degree of pain can be expected at the tissue sampling site. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator. The events intensity will be graded according to the version 5.0 of Common Terminology Criteria for Adverse Events (CTCAE) classification (grade 1 to 5 toxicity) of National Cancer Institute.
Time frame: 24 months
Incidence of urinary infection
measured at baseline (day of inclusion). This adverse event will be collected during clinical examination from blood sample analysis.
Time frame: 24 months
Incidence of urniary infection M1
measured 1 month after therapeutic administration. This adverse event will be collected during clinical examination from blood sample analysis.
Time frame: 1 month
Number of patient with urethral bleeding
measured at baseline (day of inclusion). This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator.
Time frame: 1 day
Number of patient with urethral bleeding D7
measured 7 days after therapeutic administration. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator.
Time frame: 7 days
Number of patient with urethral bleeding M1
measured 1 month after therapeutic administration. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator.
Time frame: 1 month
Number of patient with urethral bleeding M3
measured 3 months after therapeutic administration. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator.
Time frame: 3 months
Number of patient with urethral bleeding M6
measured 6 months after therapeutic administration. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator.
Time frame: 6 months
Number of patient with urethral bleeding M9
measured 9 months after therapeutic administration. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator.
Time frame: 9 months
Number of patient with urethral bleeding M18
measured 18 months after therapeutic administration. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator.
Time frame: 18 months
Number of patient with urethral bleeding M24
measured 24 months after therapeutic administration. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator. The events intensity will be graded according to the version 5.0 of Common Terminology Criteria for Adverse Events (CTCAE) classification (grade 1 to 5 toxicity) of National Cancer Institut.
Time frame: 24 months
Presence of urethral perforation with fistula or perineal soft tissue infection D7
measured 7 days after therapeutic administration. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator. The events intensity will be graded according to the version 5.0 of Common Terminology Criteria for Adverse Events (CTCAE) classification (grade 1 to 5 toxicity) of National Cancer Institut.
Time frame: 7 days
Presence of urethral perforation with fistula or perineal soft tissue infection M1
measured 1 month after therapeutic administration. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator.
Time frame: 1 month
Presence of urethral perforation with fistula or perineal soft tissue infection M3
measured 3 months after therapeutic administration. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator.
Time frame: 3 months
Presence of urethral perforation with fistula or perineal soft tissue infection M6
measured 6 months after therapeutic administration. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator.
Time frame: 6 months
Presence of urethral perforation with fistula or perineal soft tissue infection M9
measured 9 months after therapeutic administration. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator. The events intensity will be graded according to the version 5.0 of Common Terminology Criteria for Adverse Events (CTCAE) classification (grade 1 to 5 toxicity) of National Cancer Institut.
Time frame: 9 months
Presence of urethral perforation with fistula or perineal soft tissue infection M18
measured 18 months after therapeutic administration. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator.
Time frame: 18 months
Presence of urethral perforation with fistula or perineal soft tissue infection M24
measured 24 months after therapeutic administration. This adverse event will be collected during clinical examination from the investigator questioning the patient; or from the patient's unsolicited reporting, as encouraged to do towards the investigator.
Time frame: 24 months
USP score
Change from baseline Urinary Symptom Profile (USP) scores at 1, 3, 6, 9, 18 and 24 months. USP scores include 3 different scales : * low stream score. Minimum score = 0 ; Maximum score (worse outcome) = 9 * overactivity score. Minimum score = 0 ; Maximum score (worse outcome) = 21 * stress incontinence. Minimum score = 0 ; Maximum score (worse outcome) = 9
Time frame: 24 months
International Consultation on Incontinence Questionnaire Male Lower Urinary Tract Symptoms Module (ICIQ-MLUTS)
Change from baseline ICIQ-MLUTS at 1, 3, 6, 9, 18 and 24 months. Minimum score = 0 ; Maximum score (worse outcome) = 21
Time frame: 24 months
Uroflowmetry
Uroflowmetry is a noninvasive test of the voiding phase. It consists in a device which assess urine flow (Q max normal \>12ml/s, shape of the curve) and the urinated volume. To be interpreted Uroflowmetry needs to be coupled with a post micturition residual volume mesasure via an automated bladder sonography device. Urinated volume + residual volume known as bladder pre-charge and needs to be higher than 150ml to make the uroflowmetry nterpretable and meaningful. Urinary change from baseline will be measured at 1, 3, 6, 9, 18 and 24 months.
Time frame: 24 months
Baseline imaging assessment of spongiofibrosis volume with Fat Sat sequences
A magnetic-resonance imaging (MRI) will be performed locally at Screening (baseline), to assess the volume of spongiofibrosis using Sagittal view in T1 Fat Sat after Gadolinium injection.
Time frame: 24 months
imaging assessment of spongiofibrosis volume with Fat Sat sequences M1
A magnetic-resonance imaging (MRI) will be performed locally at M1 to assess the volume of spongiofibrosis using Sagittal view in T1 Fat Sat after Gadolinium injection.
Time frame: 24 months
imaging assessment of spongiofibrosis volume with Fat Sat sequences M9
A magnetic-resonance imaging (MRI) will be performed locally at M9 to assess the volume of spongiofibrosis using Sagittal view in T1 Fat Sat after Gadolinium injection.
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Time frame: 24 months
Recurrence rate
Recurrence of urethral stenosis (defined as a recurrence without a period of post procedure improvement) will be analyzed at 1, 3, 6,9 18, and 24 months.
Time frame: 24 months