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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)

Phase 0
50 Years
Open (Enrolling)
Prostate Cancer, Benign Prostatic Hyperplasia, Enlarged Prostate With Lower Urinary Tract Symptoms (LUTS)

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Trial Information

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.

Inclusion Criteria:

- Biopsy proven, clinically localized prostate cancer

- Low risk for recurrence defined as a Kattan nomogram score of less than 115, or a
serum PSA < 10ng/ml, or an individual Gleason grade of 3 or lower, or clinical stage
T2b or below.

- Candidates diagnosed with localized prostate cancer must have agreed to radical

- Voided volume greater than or equal to 125 ml.

- Maximum urinary flow less than 15 ml/sec.

- American Urological Association (AUA) symptom severity score greater than or equal to

- 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

- History of bladder stones.

- Overactive bladder without bladder outlet obstruction.

- Enrolled in another treatment trial for any disease within the past 30 days.

- Previous exposure to botulinum toxin.

- Post void residual greater than 350 ml.

- Clinically significant renal or hepatic impairment as determined by abnormal
creatinine or AST levels (based on local institutional values).

- 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 bladder; pelvic radiation, hormonal
treatment 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.

- Two documented urinary tract infections of any type in the past year (UTI defined as
greater than 100,000 colonies per ml urine from midstream clean catch or catheterized

- Patients must be off aspirin, non-steroidal anti-inflammatory drugs (NSAIDS), and
Coumadin for 7 or more days prior to botulinum toxin injection.

- 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.

- Patients will be excluded if they have depressed hematopoietic functions (platelet
count <100,000/cm3, hemoglobin <8,5 mg/dl; absolute neutrophil count <1000/cm3).

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Outcome Measure:

Determination the effects of BoNT-A injection on BPH and prostate cancer tissues.

Outcome Description:

The prostate tissue taken from each lobe will be compared to determine if the injection of BOTOX has effected the genetic profile.

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

Gusatavo E. Ayala, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Texas Houston Health Science Center


United States: Food and Drug Administration

Study ID:




Start Date:

March 2011

Completion Date:

April 2015

Related Keywords:

  • Prostate Cancer
  • Benign Prostatic Hyperplasia
  • Enlarged Prostate With Lower Urinary Tract Symptoms (LUTS)
  • Botulinum Toxin
  • Prostate Cancer
  • BPH
  • LUTS
  • Prostatic Hyperplasia
  • Hyperplasia
  • Prostatic Neoplasms



University of Texas Houston - Medical School Houston, Texas  77030