Effectiveness of onaBoNT-A vs Oral Tamsulosin in Men With BPH and LUTS

NCT ID: NCT01589263

Last Updated: 2021-10-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-01
• Study Completion Date: 2019-09-30

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.

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.

Conditions

Benign Prostatic Hyperplasia; Lower Urinary Track Symptoms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

ARM 1: onaBoNT-A + placebo

onaBoNT-A 200 U prostate injection and placebo oral capsule daily

Group Type: ACTIVE_COMPARATOR

onaBoNT-A + placebo

Intervention Type: DRUG

200 U prostate injection once

Arms: ARM 1: onaBoNT-A + placebo

Tamsulosin + placebo

Intervention Type: DRUG

0.4 mg capsule daily for 3 months Arms: ARM 2: Saline + Tamsulosin

ARM 2: Saline + Tamsulosin

Placebo prostate injection (saline) and tamsulosin 0.4 mg capsule daily.

Group Type: ACTIVE_COMPARATOR

onaBoNT-A + placebo

Intervention Type: DRUG

200 U prostate injection once

Arms: ARM 1: onaBoNT-A + placebo

Tamsulosin + placebo

Intervention Type: DRUG

0.4 mg capsule daily for 3 months Arms: ARM 2: Saline + Tamsulosin

Interventions

onaBoNT-A + placebo

200 U prostate injection once

Arms: ARM 1: onaBoNT-A + placebo

Intervention Type: DRUG

Tamsulosin + placebo

0.4 mg capsule daily for 3 months Arms: ARM 2: Saline + Tamsulosin

Intervention Type: DRUG

Other Intervention Names

Botox; Flomax

Eligibility Criteria

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

• Minimum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher P Smith, MD

Role: PRINCIPAL_INVESTIGATOR

Michael E. DeBakey VA Medical Center, Houston, TX

Locations

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, United States

Countries

United States

References

Crawford ED, Hirst K, Kusek JW, Donnell RF, Kaplan SA, McVary KT, Mynderse LA, Roehrborn CG, Smith CP, Bruskewitz R. Effects of 100 and 300 units of onabotulinum toxin A on lower urinary tract symptoms of benign prostatic hyperplasia: a phase II randomized clinical trial. J Urol. 2011 Sep;186(3):965-70. doi: 10.1016/j.juro.2011.04.062. Epub 2011 Jul 24.

Reference Type: RESULT

PMID: 21791356 (View on PubMed)

Smith CP, Chancellor MB. Emerging role of botulinum toxin in the management of voiding dysfunction. J Urol. 2004 Jun;171(6 Pt 1):2128-37. doi: 10.1097/01.ju.0000127725.48479.89.

Reference Type: RESULT

PMID: 15126771 (View on PubMed)

Chancellor MB, Fowler CJ, Apostolidis A, de Groat WC, Smith CP, Somogyi GT, Aoki KR. Drug Insight: biological effects of botulinum toxin A in the lower urinary tract. Nat Clin Pract Urol. 2008 Jun;5(6):319-28. doi: 10.1038/ncpuro1124. Epub 2008 May 6.

Reference Type: RESULT

PMID: 18461049 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

115,132

Identifier Type: OTHER

Identifier Source: secondary_id

H-27457

Identifier Type: OTHER

Identifier Source: secondary_id

CLIN-023-11F

Identifier Type: -

Identifier Source: org_study_id

NCT01567293

Identifier Type: -

Identifier Source: nct_alias