Effectiveness of onaBoNT-A vs Oral Tamsulosin in Men With Benign Prostatic Hyperplasia and Lower Urinary Track Symptoms (BPH)
Information source: Department of Veterans Affairs
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Benign Prostatic Hyperplasia; Lower Urinary Track Symptoms
Intervention: onaBoNT-A + placebo (Drug); Tamsulosin + placebo (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: Department of Veterans Affairs Official(s) and/or principal investigator(s): Christopher P Smith, MD, Principal Investigator, Affiliation: Michael E. DeBakey VA Medical Center, Houston, TX
Overall contact: Sebrina A Tello, Phone: (713) 791-1414, Ext: 5326, Email: Sebrina.Tello@va.gov
Summary
Benign prostatic hyperplasia (BPH) and its related symptoms are a common condition that
affects nearly half of men over age 50 and 90% of men over 80. Lower urinary tract symptoms
(LUTS) caused by BPH can be very troublesome, affect an individual's quality of life
significantly, and are costly.
his Phase 2 clinical research trial is a double-blind, randomized, placebo-controlled,
parallel-group study to compare the treatment effects of onaBoNT-A 200 U versus 0. 4 mg per
day of oral tamsulosin in male veterans diagnosed with moderate to severe LUTS [American
Urologic Association Symptom Score (AUASS) equal to or greater than 8] associated with BPH.
A total of 74 volunteers will be recruited to participate in this clinical trial. Volunteers
will include only males who are greater than 50 years of age and diagnosed with LUTS
associated with BPH. They are veterans who visit the Michael E. DeBakey Veterans Affairs
Medical Center - Houston (MEDVAMC). There are no eligibility restrictions as to race or
ethnicity.
Clinical Details
Official title: OnabotulinumtoxinA (onaBoNT-A) vs Oral Tamsulosin for BPH & LUTS (#02-10-10-05)
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: American Urologic Association Symptom Score (AUASS)
Detailed description:
This proposed intervention is the first randomized clinical trial comparing the effects of
onaBoNT-A prostate injection versus alpha adrenergic antagonist medication for LUTS
associated with BPH. Up to this point, clinical studies using onaBoNT-A in the prostate has
been limited to patient's refractory to - 1 adrenoceptor blocker therapy. The study will
directly compare onaBoNT-A against - 1 adrenoceptor blockers as frontline therapy in a male
veteran cohort suffering from moderate to severe LUTS. Besides its obvious efficacy in
patients' refractory to - 1 adrenoceptor blocker therapy, onaBoNTA injection has several
potential advantages over oral agents. Focal prostate injection has been shown to be safe
and obviates the systemic side effects observed with - 1 adrenoceptor blockers (i. e.
orthostatic hypotension, sexual dysfunction). In addition, most clinical studies demonstrate
a durable response to onaBoNT-A treatment exceeding 12 months. Although this study is of
modest length (i. e. total 4 years), significant results could drive paradigm shifts in how
LUTS associated with BPH is treated, even with regards to frontline therapy.
Although sophisticated molecular techniques (i. e. LCM with Microarray Analysis) have been
used by other investigators to characterize gene profile changes with BPH and LUTS, this
will be the first study examining gene profile changes in drug na ve BPH View Protocol
Record patients following treatment with the - 1 adrenoceptor blocker Tamsulosin or
onaBoNT-A. This study is important because scant knowledge exists on the true mechanisms by
which - 1 adrenoceptor blockers like Tamsulosin or onaBoNT-A improve patient urinary tract
symptoms and quality of life. It is clear, however, that nerves not only regulate prostate
growth and function but also account for LUTS that drive patients to seek therapy. This
investigation will utilize onaBoNT-A as a biological tool to identify potential novel
mechanistic pathways for future investigation that will push the development of targeted
therapy to benefit those patients refractory to all pharmacologic treatment. Potential
inflammatory pathways or neural sensory signaling alterations induced by BPH, which are
modified by onaBoNT-A or Tamsulosin to improve symptoms via gene profile changes, can be
explored by expert laboratories in the Texas Medical Center. This is a highly collaborative
project utilizing expertise across departments that will foster translational work from the
laboratory to the patient. Although not the primary goal of this study, the investigators
will also search for possible biological markers with prognostic value that could be
confirmed in a future multi-center trial.
The primary objective of this Phase 2 clinical research study is to compare the efficacy of
200 U onaBoNT-A injected into the prostate versus oral tamsulosin for the treatment of lower
urinary tract symptoms caused by BPH in male veteran volunteers at the MEDVAMC. The
secondary objective is to determine the impact of tamsulosin and onaBoNT-A on the pathologic
parameters and RNA profiles of epithelium and stroma in BPH tissues.
Volunteers will be randomized into two groups with one receiving ona-BoNT-A injection into
the prostate and an oral placebo pill taken once daily and the other group will receive a
placebo injection and an oral tamsulosin pill once daily.
Volunteers will make five clinic visits and be contacted by telephone twice
Eligibility
Minimum age: 50 Years.
Maximum age: N/A.
Gender(s): Male.
Criteria:
Inclusion Criteria:
- Males at least 50 years of age
- American Urological Association Symptom Score greater than 8
- Voided volume greater than125 ml
- Maximum urinary flowrate less than15 ml/sec.
- Must agree to all procedures and willfully consented
Exclusion Criteria:
- Any prior surgical or medical intervention for BPH
- Current diagnosis of acute or chronic prostatitis (which may cause LUTS that mimic
BPH)
- Previous exposure to onabotulinumtoxinA
- Overactive bladder without obstructive symptoms (i. e. decrease in force of stream,
hesitancy, intermittency, post-void dribbling)
- Active urinary tract disease or biopsy of the prostate within the past 6 weeks;
- 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
specimen)
- Uncontrolled diabetes
- History of bladder calculi (stones)
- Penile prosthesis or artificial urinary sphincter [placement]
- Documented bacterial or acute prostatitis within the past year
- Episode of unstable angina pectoris, myocardial infarction, transient ischemic
attack, or cerebrovascular accident (stroke) within the past 6 months
- Known primary neurologic conditions such as multiple sclerosis, myasthenia gravis or
Parkinson's disease, or other neurological diseases known to affect bladder function
- History or current evidence of carcinoma of the prostate or bladder, pelvic radiation
or surgery, urethral stricture, or bladder neck obstruction
- 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 that is likely to impede successful completion of the
study, such as certain mental disorders, hypersensitivity to onabotulinumtoxinA or
anesthetics used in the study, syncope
- Daily use of a pad or device for incontinence required
- Interested in future fertility
- Clinically significant renal or hepatic impairment
- Postvoid Residual (PVR) greater than 350 ml
- Serum prostate specific antigen (PSA) level greater than 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 (transrectal ultrasound) biopsy, percent free PSA, or other clinical
estimations in keeping with sound urologic care
- Has taken phenylephrine, pseudoephedrine, imipramine, an anticholinergic, or
cholinergic medication within the past 2 weeks
- Has taken estrogen, androgen, any drug producing androgen suppression, or anabolic
steroids within the past 4 months
- Taking aminoglycosides or any drug that interfere with neuromuscular transmission.
Eaton-Lambert syndrome, hemophilia, hereditary clotting factors deficiency, or
bleeding diathesis
- Must be off aspirin, NSAIDS, and Coumadin for 7 or more days prior to
onabotulinumtoxinA injection
- Enrolled in another treatment trial for any disease within the past 30 days
Locations and Contacts
Sebrina A Tello, Phone: (713) 791-1414, Ext: 5326, Email: Sebrina.Tello@va.gov
Michael E. DeBakey VA Medical Center, Houston, TX, Houston, Texas 77030, United States; Recruiting Christopher P Smith, MD, Phone: 713-791-1414, Email: ChristopherP.Smith@va.gov Christopher P Smith, MD, Principal Investigator
Additional Information
Starting date: June 2012
Last updated: August 12, 2015
|