Effectiveness of onaBoNT-A vs Oral Tamsulosin in Men With Benign Prostatic Hyperplasia and Lower Urinary Track Symptoms (BPH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01589263
Recruitment Status : Recruiting
First Posted : May 1, 2012
Last Update Posted : May 1, 2018
Information provided by (Responsible Party):
VA Office of Research and Development

Brief 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.

Condition or disease Intervention/treatment Phase
Benign Prostatic Hyperplasia Lower Urinary Track Symptoms Drug: onaBoNT-A + placebo Drug: Tamsulosin + placebo Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: OnabotulinumtoxinA (onaBoNT-A) vs Oral Tamsulosin for BPH & LUTS (#02-10-10-05)
Actual Study Start Date : June 1, 2012
Estimated Primary Completion Date : August 28, 2018
Estimated Study Completion Date : August 31, 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: ARM 1: onaBoNT-A + placebo
onaBoNT-A 200 U prostate injection and placebo oral capsule daily
Drug: onaBoNT-A + placebo

200 U prostate injection once

Arms: ARM 1: onaBoNT-A + placebo

Other Name: Botox

Drug: Tamsulosin + placebo
0.4 mg capsule daily for 3 months Arms: ARM 2: Saline + Tamsulosin
Other Name: Flomax

Active Comparator: ARM 2: Saline + Tamsulosin
Placebo prostate injection (saline) and tamsulosin 0.4 mg capsule daily.
Drug: onaBoNT-A + placebo

200 U prostate injection once

Arms: ARM 1: onaBoNT-A + placebo

Other Name: Botox

Drug: Tamsulosin + placebo
0.4 mg capsule daily for 3 months Arms: ARM 2: Saline + Tamsulosin
Other Name: Flomax

Primary Outcome Measures :
  1. American Urologic Association Symptom Score (AUASS) [ Time Frame: 3 months ]
    Analysis will begin with descriptive statistics. Implausible and missing values will be identified and double-checked for accuracy. Parametric methodology will be used unless measurements have tested positive for violation of normality assumption. The differences between the study subjects groups will be evaluated using the paired-samples t-tests. The clinical outcomes will be compared using Fisher's test. The criterion for significance (alpha) has been set at 0.05. All tests are 2-tailed, which means that an effect in either direction will be interpreted.

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Males at least 50 years of age
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Males at least 50 years of age
  • American Urological Association Symptom Score greater than 8
  • Voided volume greater than 125 ml
  • Maximum urinary flowrate less than 15 ml/sec.
  • Must agree to all procedures and willfully consented

Exclusion Criteria:

  • Any prior surgical intervention or use of 5-alpha-reductase 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01589263

Contact: Sebrina A Tello (713) 791-1414 ext 5326
Contact: Christopher P Smith, MD (713) 791-1414

United States, Texas
Michael E. DeBakey VA Medical Center, Houston, TX Recruiting
Houston, Texas, United States, 77030
Contact: Christopher P Smith, MD    713-791-1414   
Principal Investigator: Christopher P Smith, MD         
Sponsors and Collaborators
VA Office of Research and Development
Principal Investigator: Christopher P Smith, MD Michael E. DeBakey VA Medical Center, Houston, TX

Publications of Results:
Responsible Party: VA Office of Research and Development Identifier: NCT01589263     History of Changes
Obsolete Identifiers: NCT01567293
Other Study ID Numbers: CLIN-023-11F
115,132 ( Other Identifier: IND )
H-27457 ( Other Identifier: BCM IRB )
First Posted: May 1, 2012    Key Record Dates
Last Update Posted: May 1, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by VA Office of Research and Development:
Benign Prostatic Hyperplasia
Lower Urinary Track Symptoms

Additional relevant MeSH terms:
Prostatic Hyperplasia
Pathologic Processes
Prostatic Diseases
Genital Diseases, Male
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Urological Agents