A-botulinic Toxin for Symptomatic Benign Prostate Hypertrophy

Study Overview
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Brief Summary
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BPH is very common in elderly men, it is a stromal as well as epithelial invasion of the prostatic gland. Due to an imbalance between growth and apoptosis cellular mechanisms that are not fully elucidated. It is the same for symptomatology and urodynamic obstruction without clear identification of the part which is due to static phenomena (volume increase) and dynamic reports (α 1-receptor action). That explains the multiplicity of treatments and the difficulty of therapeutic indications between monitoring, medical treatment, and surgical operation. Experimental studies of BONT-A intra prostatic injection on animal and human models, have shown efficacy in BPH cell apoptosis, decrease in cell growth and decline in the number of adrenergic α1 receptors. Many studies in humans show therapeutic efficacy leading to a possible use of BONT-A as mini invasive treatment of symptomatic BPH, as an alternative to medical or surgical treatment. PROTOX study proposes to evaluate tolerance and effectiveness of the intra-prostatique BONT-A injection in the treatment of symptomatic BPH.

Official Title
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Study of the Effectiveness and the Tolerance of Intraprostatic A-botulinic Toxin Injection, in the Treatment of Symptomatic Benign Prostate Hypertrophy.

Conditions
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Prostatic Hyperplasia

Intervention / Treatment
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* Drug: BONT-A intra-prostatic injection
* Drug: Optimized medical BPH treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient aged 50 to 85; Obstructive or irritative urinary symptomatology linked to a BPH; Score IPSS moderate to severe (8-19: moderate; 20-35: severe) or IPSS ≤ 7 in patient medically treated for symptomatic BPH; Increase in prostate volume on the rectal touch or ultrasound; Free consent, informed and written, dated and signed by the patient and the investigator (at the latest the day inclusion and before any examination requires the study); Subject affiliate or beneficiary of a social protection Exclusion Criteria: stenosis of the urethra confirmed by endoscopic or radiological examination; prostate cancer suspicion; medical past history of surgery, radiotherapy or pelvic trauma (, breach of the urethra, pubic symphysis disjunction); surgical resection of the prostate (adenomecty); clinical or paraclinical signs of vesical sphincterial disynergia; chronic urinary retention > 500 ml; BPH complications making surgery necessary: effects on the upper urinary tract: dilatation or renal obstructive insufficiency, bladder stones or diverticula. patient previously treated by botulic toxin (whatever injection site); Persons unable to understand the course of the study.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BONT-A intra-prostatic injection<br> | Drug: BONT-A intra-prostatic injection<br>* • Intra prostatic injection of 200 IU of BONT-A (2 x 100 IU to dilute in 10 cc salted serum), divided into 4 injections, 2 in each prostate lobe for a volume intra injected 2.5 cc per site. Interruption of the medical therapy 1 month after the injection;<br>|
| Active Comparator: optimized medical BPH treatment<br> | Drug: Optimized medical BPH treatment<br>* Optimization of the medical therapy according to recent guidelines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the patient with auto-questionnaire IPSS urinary symptomatology: questions 1 to 7 (0 to 35 score). |  | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IPSS question 8 (score 0 to 6) |  | 18 months | 
| Uroflowmetry (Qmax in ml/s) |  | 18 months | 
| • measure the post-voiding residue assessed by supra pubic ultrasound or urinary drainage |  | 18 months | 
| measure of prostate volume assessed by endo-rectal ultrasound |  | 18 months | 
| measurement of the erectile function by auto questionnaire IIEF-5 (0 to 24 score) |  | 18 months | 
| urinary continence Evaluation by ICS 1 (0 to 23 score) and ICS 2 (0 to 12 score) |  | 18 months | 
| bladder emptying mode (spontaneous or permanent probe) |  | 18 months | 
| specific treatment for BPH (alpha blocking, 5 alpha reductase inhibitor and/or phytotherapy) |  | 18 months | 
| Urinary retention |  | 18 months | 
| Surgical treatment |  | 18 months | 
| profile of gene and protein expression on the first urine flow after prostate massage |  | 18 months |