Botulinum Toxin Injection With Prostate Brachytherapy
Lower Urinary Tract Symptoms
Radioactive Seed Implantation
Drug: Botox injection
Drug: Saline injection
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Botulinum Toxin Injection With Prostate Brachytherapy: A Randomized, Placebo-controlled Study Monitoring Urinary Symptoms and PSA|
- Urinary symptoms [ Time Frame: Weekly for 4 weeks, monthly thereafter until 1 year ] [ Designated as safety issue: No ]
- PSA [ Time Frame: 1 mo, 3 mo, 6 mo, 9 mo, 1 year, 15 mo, 18 mo, 24 mo ] [ Designated as safety issue: No ]
|Estimated Study Completion Date:||July 2012|
|Estimated Primary Completion Date:||July 2012 (Final data collection date for primary outcome measure)|
Drug: Botox injection
Intraprostatic injection of Botox (100 units for < 30 cc prostate; 200 units for > 30 cc prostate) administering 2 transperineal injections into both lateral lobes of the prostate (25-50 units per injection), just 5-10 mm proximal to the bladder neck.
Other Name: Botox
Placebo Comparator: B
Drug: Saline injection
Saline injection, administering 2 transperineal injections into both lateral lobes of the prostate (1-2 cc per injection), just 5-10 mm proximal to the bladder neck.
Other Name: NS
Brachytherapy is a popular treatment modality for localized prostate cancer, where radioactive seeds are implanted through 18 gauge needles into the prostate via a perineal template with rectal ultrasound guidance. The radioactivity is delivered over several months, depending on the isotope used. During this time, there can be exacerbation of urinary voiding symptoms from early edema of the prostate gland due to the implantation procedure, then later from the inflammatory reaction of the radiation. Because the initial acute inflammation may persist for many months despite steadily declining doses of radiation, attempts are made to minimize urinary symptoms prior to brachytherapy with pharmacologic therapy (alpha-blockers) or minimally invasive surgical therapy (transurethral incision or limited transurethral resection to avoid significant distortion of the prostate parenchyma for future seed implantation). Even with these precautions, around 30-40% of brachytherapy patients will still develop voiding symptoms. With such bothersome symptoms, intervention is deferred for at least 8-10 months to avoid distorting the planned field of radiation. Once symptoms develop, various additional pharmacologic measures are employed, such as increased doses of alpha-blockers, medrol steroid taper, and non-steroidal anti-inflammatory agents. Some patients require intermittent self-catheterization or suprapubic catheter for urinary diversion.
Botulinum toxin has been used for cosmetic uses, and has been successfully used for treatment of overactive bladder, external sphincter dyssynergia, and benign prostatic hyperplasia (BPH). The studies with BPH show reduction in symptoms scores, PSA, and prostate volume, the latter from atrophy due to the denervation effect. The response lasts for 6-9 months.
We propose to study botox intraprostatic injection during brachytherapy to see whether this improves urinary symptoms or avoids need for urinary tract instrumentation over this 6-8 month post-operative period when one wants to avoid manipulating the radioactive seeds. We will also monitor PSA, and see if there is any measurable augmentation of PSA decline with botox + Brachytherapy vs Brachytherapy alone. We will randomize patients to botox (100 units for < 30 cc prostate; 200 units for > 30 cc prostate) vs saline injection, administering 2 transperineal injections into both lateral lobes of the prostate (25-50 mg per injection), just 5-10 mm proximal to the bladder neck.
N= 60 (30 receive Botox, 30 receive saline)
AUA Symptoms scores weekly for 4 weeks, monthly thereafter Medications for urinary symptoms Need for catheterization PSA checked at 1 mo, 3 mo, 6 mo, 9 mo, 1 year, 15 mo, 18 mo, 24 mo
Please refer to this study by its ClinicalTrials.gov identifier: NCT00681148
|United States, Georgia|
|Emory Clinic, Emory University Hospital|
|Atlanta, Georgia, United States, 30322|
|Principal Investigator:||Peter T Nieh, MD||Emory University SOM|