A Randomized Double-blind Placebo-controlled Phase 2 Dose-ranging Study of OnabotulinumtoxinA in Men with Benign Prostatic Hyperplasia

Marberger, Michael; Chartier‐Kastler, Emmanuel; Egerdie, Blair; Lee, Kyu‐Sung; Grosse, Joachim; Bugarin, Denise; Zhou, Jihao; Patel, Anand; Haag‐Molkenteller, Cornelia

doi:10.1016/j.eururo.2012.10.005

Cited by 97 publications

(66 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Clinical studies investigating the role of neural influences on LUTS/BPH are underway. 34 The presence of an age limited neural-epithelial response following neural perturbation is an interesting finding in our model. Several investigators have demonstrated reduced age-related plasticity of neurotrophin receptor expression in selected sympathetic neurons of the rat.…”

Section: Discussionmentioning

confidence: 79%

Nerve growth factor signaling following unilateral pelvic ganglionectomy in the rat ventral prostate is age dependent

Podlasek

Ghosh²,

Çakır³

et al. 2013

Asian J Androl

View full text Add to dashboard Cite

Benign prostatic hyperplasia (BPH) is a serious health concern and is an underlying cause of lower urinary tract symptoms (LUTS) in many men. In affected men, LUTS/BPH is believed to result from benign proliferation of the prostate resulting in bladder outlet obstruction. Postnatal growth of the prostate is controlled via growth factor and endocrine mechanisms. However, little attention had been given to the function of the autonomic nervous system in prostate growth and differentiation. Nerve growth factor (NGF) is a prostatic mitogen that has a trophic role in autonomic sensory end organ interaction. In this study, we examine how the autonomic nervous system influences prostate growth as a function of age by quantifying NGF in the rat ventral prostate (VP) after pelvic ganglionectomy. Unilateral pelvic ganglionectomy was performed on postnatal days 30 (P30), 60 and 120 Sprague-Dawley rats in comparison to sham controls (n539). Semiquantitative RT-PCR, Western blotting and immunohistochemical analysis for NGF were performed on denervated, intact (contralateral side) and sham control VP 7 days after surgery. Ngf RNA expression was significantly increased in the denervated and intact hyperplastic VP. Western blotting showed age-dependent increases in NGF protein at P60 in the contralateral intact VP. NGF was localized in the nerves, basal cells and columnar epithelium of the prostatic ducts. Denervation causes age-dependent increases in NGF in the VP, which is a potential mechanism by which the autonomic nervous system may regulate prostate growth and lead to BPH/LUTS. Asian Journal of Andrology (2013) Keywords: denervation; nerve growth factor; prostate growth; ventral prostate INTRODUCTION Benign prostatic hyperplasia (BPH) is a serious health concern worldwide and is an underlying cause of many lower urinary tract symptoms (LUTS). LUTS is common in aging men and a population based survey performed in five countries reports that ,64% of adults experience at least one LUTS symptom.1 LUTS has a profound impact on social functioning and quality of life in affected men 2,3 with similar effects reported as after a heart attack or stroke.4 BPH can induce acute urinary retention, incontinence, recurrent urinary tract infection or obstructive uropathy. LUTS secondary to BPH generally consists of three components: benign proliferation of the stroma and epithelium, bladder outlet obstruction and symptoms resulting from obstruction.

show abstract

Section: Discussionmentioning

confidence: 79%

Nerve growth factor signaling following unilateral pelvic ganglionectomy in the rat ventral prostate is age dependent

Podlasek

Ghosh²,

Çakır³

et al. 2013

Asian J Androl

View full text Add to dashboard Cite

show abstract

“…In an analysis of a different prostate injectable, Elhilali et al [60] found a significant placebo response that made it difficult for their injectable protein to demonstrate a statistically significant improvement over placebo. Similar to the endoscopic procedures, increases in Qmax were often pronounced with improvement over 1.5 mL/s commonly seen [57,58].…”

Section: Surgical Treatmentsmentioning

confidence: 87%

“…In the first study looking at injection of botox, no significant response was noted to injection of normal saline [59] with each study afterwards showing a pronounced response. Work by Marberger et al [57] and McVary et al [58] found decreases in AUASS of 27 and 26 %, respectively, in the groups injected with saline. In an analysis of a different prostate injectable, Elhilali et al [60] found a significant placebo response that made it difficult for their injectable protein to demonstrate a statistically significant improvement over placebo.…”

Section: Surgical Treatmentsmentioning

confidence: 96%

“…Studies utilizing prostatic injection have an equally pronounced sham surgical response and this surprising decreases in symptom scores has likely led to the failure of at least botulinum toxin (botox) for prostate injections [57,58]. In the first study looking at injection of botox, no significant response was noted to injection of normal saline [59] with each study afterwards showing a pronounced response.…”

Section: Surgical Treatmentsmentioning

confidence: 98%

See 1 more Smart Citation

Placebo Medication and Sham Surgery Responses in Benign Prostatic Hyperplasia Treatments: Implications for Clinical Trials

2015

View full text Add to dashboard Cite

Placebo medications and sham surgeries have long been thought to be inert treatments. These groups served as a threshold to which an active treatment should be compared in a randomized trial to determine the true efficacy of the active treatment. However, surprising changes in subjective symptom scores and objective measures of voiding have been demonstrated in numerous placebo medication or sham surgery arms of trials. The exact mechanisms by which these inactive treatments augment patient outcomes are not clearly defined and multiple theories have been proposed to explain the often pronounced response. It appears that urologic outcomes are particularly prone to these effects and the astute physician should keep these responses in mind when interpreting any trial on a new therapy.

show abstract

“…The clinical efficacy and safety of different dose ranges of BoNT-A (100 U-300 U) have Nature Reviews | Urology been assessed in several non-placebo-controlled clinical trials. [62][63][64][65][66][67][68] As the overall efficacy and safety of the various doses of BoNT-A tested thus far are similar, 62,63 preference might be given to lower doses owing to reduced costs and fewer adverse events. However, the studies have shown no consistency in clinical response in terms of outcome parameters such as symptom scores (for example, the American Urological Association Symptom Index [AUASI] and the International Prostate Symptom Score [IPSS]), reduction in prostate volume, postvoid residual urine volume, peak urinary flow rate (Q max ) and PSA (Table 1).…”

Section: Mechanism Of Actionmentioning

confidence: 99%

New intraprostatic injectables and prostatic urethral lift for male LUTS

2015

View full text Add to dashboard Cite

Treatment modalities for male lower urinary tract symptoms (LUTS) comprise a broad spectrum of medical and surgical options. Interest is growing in minimally invasive treatment options, which should ideally be performed in an outpatient setting and have a short recovery time, durable efficacy and a good safety profile. The preservation of all aspects of sexual function, including antegrade ejaculation, seems to be increasingly important for patients. Initial experimental data on new minimally invasive procedures-such as the intraprostatic injection of novel agents including botulinum neurotoxin A (BoNT-A), NX-1207 and PRX302-were promising, but clinical trials have not confirmed the findings. Trials of the mechanical prostatic urethral lift device-Urolift(®) (Neotract, Inc., USA)-have been positive, but further long-term results are needed to confirm its beneficial effects.

show abstract

A Randomized Double-blind Placebo-controlled Phase 2 Dose-ranging Study of OnabotulinumtoxinA in Men with Benign Prostatic Hyperplasia

Cited by 97 publications

References 25 publications

Nerve growth factor signaling following unilateral pelvic ganglionectomy in the rat ventral prostate is age dependent

Nerve growth factor signaling following unilateral pelvic ganglionectomy in the rat ventral prostate is age dependent

Placebo Medication and Sham Surgery Responses in Benign Prostatic Hyperplasia Treatments: Implications for Clinical Trials

New intraprostatic injectables and prostatic urethral lift for male LUTS

Contact Info

Product

Resources

About