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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Incidence of urinary infection
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Control group
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.
干预措施: lipoaspiration (Procedure)
Control group
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.
干预措施: urethrotomy (Procedure)
Experimental group
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.
干预措施: lipoaspiration (Procedure)
Experimental group
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.
干预措施: urethrotomy (Procedure)
Experimental group
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.
干预措施: autologous ADSVF administration (Drug)
结局指标
主要结局
Incidence of urinary infection
时间窗: 24 months
measured at baseline (day of inclusion). This adverse event will be collected during clinical examination from blood sample analysis.
Incidence of urniary infection M1
时间窗: 1 month
measured 1 month after therapeutic administration. This adverse event will be collected during clinical examination from blood sample analysis.
Number of patient with urethral bleeding
时间窗: 1 day
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.
Baseline intensity and duration of urethral pain
时间窗: 1 day
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.
Intensity and duration of urethral pain D7
时间窗: 7 days
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.
Intensity and duration of urethral pain M1
时间窗: 1 month
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.
Intensity and duration of urethral pain M3
时间窗: 3 months
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.
Intensity and duration of urethral pain M18
时间窗: 18 months
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.
Intensity and duration of urethral pain M24
时间窗: 24 months
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.
Presence of urethral perforation with fistula or perineal soft tissue infection M9
时间窗: 9 months
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.
Presence of urethral perforation with fistula or perineal soft tissue infection M18
时间窗: 18 months
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.
Presence of urethral perforation with fistula or perineal soft tissue infection M24
时间窗: 24 months
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.
Intensity and duration of urethral pain M6
时间窗: 24 months
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.
Intensity and duration of urethral pain M9
时间窗: 9 months
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.
Number of patient with urethral bleeding D7
时间窗: 7 days
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.
Number of patient with urethral bleeding M1
时间窗: 1 month
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.
Number of patient with urethral bleeding M3
时间窗: 3 months
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.
Number of patient with urethral bleeding M6
时间窗: 6 months
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.
Number of patient with urethral bleeding M9
时间窗: 9 months
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.
Number of patient with urethral bleeding M18
时间窗: 18 months
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.
Number of patient with urethral bleeding M24
时间窗: 24 months
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.
Presence of urethral perforation with fistula or perineal soft tissue infection D7
时间窗: 7 days
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.
Presence of urethral perforation with fistula or perineal soft tissue infection M1
时间窗: 1 month
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.
Presence of urethral perforation with fistula or perineal soft tissue infection M3
时间窗: 3 months
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.
Presence of urethral perforation with fistula or perineal soft tissue infection M6
时间窗: 6 months
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.
次要结局
- USP score(24 months)
- International Consultation on Incontinence Questionnaire Male Lower Urinary Tract Symptoms Module (ICIQ-MLUTS)(24 months)
- Uroflowmetry(24 months)
- Baseline imaging assessment of spongiofibrosis volume with Fat Sat sequences(24 months)
- imaging assessment of spongiofibrosis volume with Fat Sat sequences M1(24 months)
- imaging assessment of spongiofibrosis volume with Fat Sat sequences M9(24 months)
- Recurrence rate(24 months)