Clinical trial NCT05857371: Safety and Potential Effect of Innovative Treatment by Adjuvant Injection of Stromal Vascular Fraction From Autologous Adipose Tissue of URethral Stenosis With Endoscopic Urethrotomy
Official title: Safety and Potential Effect of Innovative Treatment by Adjuvant Injection of Stromal Vascular Fraction From Autologous Adipose Tissue of URethral Stenosis With Endoscopic Urethrotomy: Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Urethral Stenosis
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
First posted: 2023-05-12
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Male, aged from 18 to 85 years
* Bulbar urethral stenosis ≤ 3 cm.
* At least one urethral dilatation or urethrotomy for the bulbar stenosis in the past 24 months before diagnosis of stenosis
* Ability to avoid corticoids or immunosuppressive drugs one month after treatment. For any patients with either corticoid or immunosuppressive treatment the physician in charge of this treatment will be contacted and asked to give a written approval for one month cessation of the therapy
* Good general health status according to clinical history and a physical examination
* BMI \> 18 to insure adequate access to abdominal or other subcutaneous adipose tissue for adipose tissue harvesting

Exclusion Criteria:

* Urethral stenosis of other location than bulbar
* Urethral stenosis length \> 3 cm
* Urethral stenosis on reconstructed penis (transgender, post amputation)
* Prior perineal or pelvic radiotherapy
* Concurrent urinary tract infection without treatment
* Concurrent perineal infection
* Penile cancer \< 5 years
* Current or recent history of abnormal, severe, progressive, uncontrolled infectious, hepatic, haematological, gastrointestinal (except CD), endocrine, pulmonary, cardiac, neurological, psychiatric, or cerebral disease
* Congenital or acquired immunodeficiencies
* Contraindication to the anaesthetic or surgical procedure
* Corticoids or immunosuppressive drugs \> 3 months
* Any active viral infection among the following: HIV, HTLV I and II, VHB, VHC and syphillis
* Administrative restricted rights
* Presence of signs of obstructive voiding symptoms not directly attributable to the stricture at the discretion of the physician
* Diagnosis of untreated and unresolved BPH benign prostatic hyperplasia or BNC bladder neck contracture
* Diagnosis of carcinoma of the urethra, bladder or prostate within the last two (2) years

Primary outcomes:
measure: Baseline intensity and duration of urethral pain
timeFrame: 1 day
measure: Intensity and duration of urethral pain D7
timeFrame: 7 days
measure: Intensity and duration of urethral pain M1
timeFrame: 1 month
measure: Intensity and duration of urethral pain M3
timeFrame: 3 months
measure: Intensity and duration of urethral pain M6
timeFrame: 24 months
measure: Intensity and duration of urethral pain M9
timeFrame: 9 months
measure: Intensity and duration of urethral pain M18
timeFrame: 18 months
measure: Intensity and duration of urethral pain M24
timeFrame: 24 months
measure: Incidence of urinary infection
timeFrame: 24 months
measure: Incidence of urniary infection M1
timeFrame: 1 month
measure: Number of patient with urethral bleeding
timeFrame: 1 day
measure: Number of patient with urethral bleeding D7
timeFrame: 7 days
measure: Number of patient with urethral bleeding M1
timeFrame: 1 month
measure: Number of patient with urethral bleeding M3
timeFrame: 3 months
measure: Number of patient with urethral bleeding M6
timeFrame: 6 months
measure: Number of patient with urethral bleeding M9
timeFrame: 9 months
measure: Number of patient with urethral bleeding M18
timeFrame: 18 months
measure: Number of patient with urethral bleeding M24
timeFrame: 24 months
measure: Presence of urethral perforation with fistula or perineal soft tissue infection D7
timeFrame: 7 days
measure: Presence of urethral perforation with fistula or perineal soft tissue infection M1
timeFrame: 1 month
measure: Presence of urethral perforation with fistula or perineal soft tissue infection M3
timeFrame: 3 months
measure: Presence of urethral perforation with fistula or perineal soft tissue infection M6
timeFrame: 6 months
measure: Presence of urethral perforation with fistula or perineal soft tissue infection M9
timeFrame: 9 months
measure: Presence of urethral perforation with fistula or perineal soft tissue infection M18
timeFrame: 18 months
measure: Presence of urethral perforation with fistula or perineal soft tissue infection M24
timeFrame: 24 months
Secondary outcomes:
measure: USP score
timeFrame: 24 months
measure: International Consultation on Incontinence Questionnaire Male Lower Urinary Tract Symptoms Module (ICIQ-MLUTS)
timeFrame: 24 months
measure: Uroflowmetry
timeFrame: 24 months
measure: Baseline imaging assessment of spongiofibrosis volume with Fat Sat sequences
timeFrame: 24 months
measure: imaging assessment of spongiofibrosis volume with Fat Sat sequences M1
timeFrame: 24 months
measure: imaging assessment of spongiofibrosis volume with Fat Sat sequences M9
timeFrame: 24 months
measure: Recurrence rate
timeFrame: 24 months
Other outcomes:
Locations:
city: Marseille
country: France
facility: Assistance Publique Hopitaux de Marseille
Study officials:
affiliation: ASSISITANCE PUBLIQUE HOPITAUX DE MARSEILLE
name: FRANCOIX CREMIEUX
role: STUDY_DIRECTOR
References: