Botulinum Toxin Injection for the Management of BPH

Study Overview
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Brief Summary
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This is a double-blind randomized phase II trial to determine whether two different doses of BoNT/A injection into the prostate gland demonstrate sufficient improvement in the management of lower urinary symptoms due to BPH to warrant more extensive research. Subjects will receive either a 100U or 300U dose. Participation will last 1 year.

Official Title
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Intraprostatic Injection of Botulinum Toxin for the Management of Benign Prostatic Hyperplasia: A Randomized Phase II Trial

Conditions
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Benign Prostatic Hyperplasia

Intervention / Treatment
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* Drug: botulinum toxin type A (BoNT/A)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male at least 50 years of age. Voided volume => 125 ml. Maximum urinary flow < 15 ml/sec. AUA symptom severity score => 8. Patient signed informed consent prior to the performance of any study procedures. Patient able to complete the study protocol in the opinion of the investigator. Exclusion Criteria: Any prior surgical intervention for BPH. Current diagnosis of acute or chronic prostatitis (which may cause LUTS that mimic BPH). Overactive bladder without bladder outlet obstruction. Enrolled in another treatment trial for any disease within the past 30 days. Men interested in future fertility. Previous exposure to botulinum toxin. On alpha-blocker within the past 48 hours. On any 5-alpha-reductase inhibitor within the past month. Post void residual > 350 ml. On phenylephrine, pseudoephedrine, imipramine, an anticholinergic, or cholinergic medication within the past 2 weeks. On estrogen, androgen, any drug producing androgen suppression, or anabolic steroids within the past 4 months. Clinically significant renal or hepatic impairment as determined by abnormal creatinine or AST levels (based on local institutional values). Serum prostate specific antigen level > 8 ng/ml (Hybritech). For those with a PSA between 4-8 ng/ml, the PSA elevation must be considered to be from a benign cause in the opinion of the PI. This decision can be based on PSA velocity, previous TRUS biopsy, percent free PSA, or other clinical estimations in keeping with sound urologic care. Active urinary tract disease or biopsy of the prostate within the past 6 weeks. Daily use of a pad or device for incontinence required. Episode of unstable angina pectoris, myocardial infarction, transient ischemic attack, or cerebrovascular accident (stroke) within the past 6 months. On aminoglycosides or any drug that interfere with neuromuscular transmission. Eaton-Lambert syndrome, hemophilia, hereditary clotting factors deficiency, or bleeding diathesis. Penile prosthesis or artificial urinary sphincter. History or current evidence of carcinoma of the prostate or bladder, pelvic radiation or surgery, urethral stricture, or bladder neck obstruction. Known primary neurologic conditions such as multiple sclerosis, myasthenia gravis or Parkinson's disease, or other neurological diseases known to affect bladder function. Documented bacterial or acute prostatitis within the past year. Two documented urinary tract infections of any type in the past year (UTI defined as > 100,000 colonies per ml urine from midstream clean catch or catheterized specimen). History of bladder calculi. Patients must be off aspirin, NSAIDS, and Coumadin for 7 or more days prior to botulinum toxin injection. Cancer that is not considered cured, except basal cell or squamous cell carcinoma of the skin (cured defined as no evidence of cancer within the past 5 years). Any serious medical condition likely to impede successful completion of the study, such as certain mental disorders, hypersensitivity to botulinum toxin or anesthetics used in the study, syncope, uncontrolled diabetes.

Ages Eligible for Study
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Minimum Age: 50 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>100 units botulinum toxin type A (BoNT/A) | Drug: botulinum toxin type A (BoNT/A)<br>* 100 unit and 300 unit dosages: Dilute each 100 U vial with 1.3 ml of normal saline. Each reconstituted vial is then drawn up into a single syringe with a total of 4 ml = 300 U. The instrument used to inject the botulinum toxin is an ultrasound device with a transrectal ultrasound probe specially designed for prostate biopsies which has a special canal to introduce and direct a needle in to the selected prostatic area.<br>* Other names: marketed in the US as BOTOX by Allergan;|
| Active Comparator: 2<br>300 units botulinum toxin type A (BoNT/A) | Drug: botulinum toxin type A (BoNT/A)<br>* 100 unit and 300 unit dosages: Dilute each 100 U vial with 1.3 ml of normal saline. Each reconstituted vial is then drawn up into a single syringe with a total of 4 ml = 300 U. The instrument used to inject the botulinum toxin is an ultrasound device with a transrectal ultrasound probe specially designed for prostate biopsies which has a special canal to introduce and direct a needle in to the selected prostatic area.<br>* Other names: marketed in the US as BOTOX by Allergan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in the AUA Symptom Score Index by 30% From Baseline Within the First 12 Weeks After Injection. | The primary outcome was treatment success at 3 months post-treatment, defined as (1) improvement in the AUASI by at least 30% and/or (2) Qmax improvement of more than 30%, each determined from baseline to 3 months after injection. In addition, two safety criteria also had to be met; a dose failed if (1) any reported event was determined to be related to the onabotulinum toxin A injection and was considered life threatening, disabling, or fatal or (2) >=40% of the participants reported a moderate or severe side effect related to the botulinum toxin injection. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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benign prostatic hyperplasia, BPH, botulinum toxin, BoNT/A