H-25362: Effect of Botulinum Neurotoxin Type A Prostate Injections on Neurogenesis and Gene Profile Expression in Men With Localized Prostate Cancer and Lower Urinary Tract Symptoms/BPH (Protocol # 05-09-30-03)
For the purposes of this study, patients are treated with the presentation of botulinum
toxin type A which is marketed in the U.S. as BOTOX® by Allergan. BOTOX® is a purified
neurotoxin complex supplied as a sterile, vacuum dried purified botulinum toxin type A,
produced from fermentation of Clostridium botulinum type A.
A primary aim of this study is to determine the molecular effects of BoNT-A injection on
human BPH tissues. While the majority of BoNT-A injections in humans target BPH in the
transition zone, innervation is most abundant in the peripheral zone of the prostate where
the majority of prostate cancers develop. In fact, recent studies have demonstrated the
importance of neurogenesis and axogenesis in the spread of human prostate cancer. In
addition, in vitro studies have shown that BoNT-A has antiproliferative effects on human
prostate cancer cell lines.
Thus, a second aim of this proposal is to determine profile changes in high-grade prostatic
intraepithelial neoplasia (HGPIN) and prostate cancer following BoNT-A injection into the
peripheral zone. The investigators will also determine the effects of BoNT-A on the genetic
profile of normal tissue. The investigators study population will be men with clinically
localized prostate cancer. Men will be injected on one side in both their transition and
peripheral zones with 100U BoNT-A (i.e. Botox®, Allergan, Inc.), respectively, one month
prior to their scheduled radical prostatectomy. Sham saline injection of the other side of
the prostate (transition and peripheral zones) will be used as an internal control. The
investigators will inject the other lobe of the prostate with saline to account for any
denervating effects of "wet needling." Patients will undergo radical prostatectomy without
any changes to standard of care. The strategy has been used in the investigators Institution
previously to determine the efficacy of gene therapy 22 and targeted drugs. However, and
unlike the investigators previous neoadjuvant trials, the investigators will not power this
study to look at the effects of Botox on biochemical recurrence free survival. This study
only has biologic endpoints and no survival endpoints."
A third aim of the study will be to examine changes in vas deferens function following
prostate treatment with BoNT-A. The investigators plan to harvest a 2.5 cm segment from the
distal vas deferens on either side (i.e. Saline treated and BoNT-A treated) before entry
into the prostate will be isolated and placed in oxygenated krebs solution for transport to
the research laboratory.
Patients will have 3 visits to the clinic and two telephone calls during their participation
in this study. The last visit is about 4 weeks after the injection.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Determination the effects of BoNT-A injection on BPH and prostate cancer tissues.
The prostate tissue taken from each lobe will be compared to determine if the injection of BOTOX has effected the genetic profile.
Gusatavo E. Ayala, MD
University of Texas Houston Health Science Center
United States: Food and Drug Administration
|University of Texas Houston - Medical School||Houston, Texas 77030|