Safety and Potential Effect of Innovative Treatment by Adjuvant Injection of Stromal Vascular Fraction From Autologous Adipose Tissue of URethral Stenosis With Endoscopic Urethrotomy (SURF)

Public Assistance-Hospitals of Marseille (AP-HM)

Status and phase: Enrolling; Phase 2

Conditions: Urethral Stenosis

Treatments: Procedure: urethrotomy; Drug: autologous ADSVF administration; Procedure: lipoaspiration

Study type: Interventional

Funder types: Other

Identifiers

NCT05857371

RCAPHM18_0020_1

2022-002175-11 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 20 estimated patients

Sex: Male

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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20 participants in 2 patient groups

Control group

Sham Comparator group

Description:

The surgeon trained to lipoaspiration procedure will perform lipoaspiration for the ADSVF cryopreservation under local anesthesia with sedation. The patients of the control group benefices to urethrotomy (standard care) under general anesthesia. The surgical surgical technique necessitates performing three incisions with a cold endoscopic knife in the stenosis to obtain enlargement of urethral lumen on the length of the fibrosis at 3, 9 and 12 o' clock. For patients randomised in the control group, lippoaspiration will be performed for cryopreservation of the autologous ADSVF and potential second administration of ADSVF in case of UrS recurrency. UrS recurrence or primary failure is defined as a recurrence without a period of post procedure improvement). Recurrence incoming before 21 months post experimental treatment will be treated according to the study in order to have a minimum follow-up of 3 months.

Treatment:

Procedure: lipoaspiration

Procedure: urethrotomy

Experimental group

Experimental group

Description:

The surgeon trained to lipoaspiration procedure will perform lipoaspiration for the ADSVF cryopreservation under local anesthesia with sedation. The patients of the control group benefices to urethrotomy (standard care) under general anesthesia. The surgical surgical technique necessitates performing three incisions with a cold endoscopic knife in the stenosis to obtain enlargement of urethral lumen on the length of the fibrosis at 3, 9 and 12 o' clock. For theses patients -randomised in the experimental group - the experimental cell drug will be customised-made to each patient's lesion and included a dose between 16 and 56 million\* viable nucleated cells (VNCs) of fresh or thawed autologous Adipose-derived -Stromal Vascular Fraction, resuspended in saline (0, 9%) - 5% human serum albumin (50 mg/mL) final packaged in 2 to 7 syringes of 1 mL at a concentration of 8 million CNV / mL, individually closed with a tamper-proof Luer Lock cap and labelled to ensure double-blindness.

Treatment:

Procedure: lipoaspiration

Drug: autologous ADSVF administration

Procedure: urethrotomy