A-botulinic Toxin for Symptomatic Benign Prostate Hypertrophy

Prostatic Hyperplasia Clinical Trial

— PROTOX  

Official title:

Study of the Effectiveness and the Tolerance of Intraprostatic A-botulinic Toxin Injection, in the Treatment of Symptomatic Benign Prostate Hypertrophy.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01275521
• Other study ID #: CHUBX 2010/39
• Status: Completed
• Phase: Phase 3
• First received: January 11, 2011
• Last updated: August 22, 2017
• Start date: January 10, 2011
• Est. completion date: April 28, 2015

Study information

• Verified date: August 2017
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

BPH is very common in elderly men, it is a stromal as well as epithelial invasion of the prostatic gland. Due to an imbalance between growth and apoptosis cellular mechanisms that are not fully elucidated. It is the same for symptomatology and urodynamic obstruction without clear identification of the part which is due to static phenomena (volume increase) and dynamic reports (α 1-receptor action). That explains the multiplicity of treatments and the difficulty of therapeutic indications between monitoring, medical treatment, and surgical operation. Experimental studies of BONT-A intra prostatic injection on animal and human models, have shown efficacy in BPH cell apoptosis, decrease in cell growth and decline in the number of adrenergic α1 receptors.

Many studies in humans show therapeutic efficacy leading to a possible use of BONT-A as mini invasive treatment of symptomatic BPH, as an alternative to medical or surgical treatment.

PROTOX study proposes to evaluate tolerance and effectiveness of the intra-prostatique BONT-A injection in the treatment of symptomatic BPH.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: April 28, 2015
• Est. primary completion date: April 28, 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 50 Years to 85 Years

Eligibility

Inclusion Criteria:

• Patient aged 50 to 85;

• Obstructive or irritative urinary symptomatology linked to a BPH;

• Score IPSS moderate to severe (8-19: moderate; 20-35: severe) or IPSS = 7 in patient medically treated for symptomatic BPH;

• Increase in prostate volume on the rectal touch or ultrasound;

• Free consent, informed and written, dated and signed by the patient and the investigator (at the latest the day inclusion and before any examination requires the study);

• Subject affiliate or beneficiary of a social protection

Exclusion Criteria:

• stenosis of the urethra confirmed by endoscopic or radiological examination;

• prostate cancer suspicion;

• medical past history of surgery, radiotherapy or pelvic trauma (, breach of the urethra, pubic symphysis disjunction);

• surgical resection of the prostate (adenomecty);

• clinical or paraclinical signs of vesical sphincterial disynergia; chronic urinary retention > 500 ml;

• BPH complications making surgery necessary: effects on the upper urinary tract:

dilatation or renal obstructive insufficiency, bladder stones or diverticula.

• patient previously treated by botulic toxin (whatever injection site);

• Persons unable to understand the course of the study.

Related Conditions & MeSH terms

• Hyperplasia
• Hypertrophy
• Prostatic Hyperplasia

Intervention

Drug:
• BONT-A intra-prostatic injection
• Intra prostatic injection of 200 IU of BONT-A (2 x 100 IU to dilute in 10 cc salted serum), divided into 4 injections, 2 in each prostate lobe for a volume intra injected 2.5 cc per site. Interruption of the medical therapy 1 month after the injection;
• Optimized medical BPH treatment
Optimization of the medical therapy according to recent guidelines

Locations

Country	Name	City	State
France	Service d'Urologie - CH du Pays d'Aix - Avenue de Tamaris	AIX-en-PROVENCE
France	Service d'Urologie, CHU d'Angers 4, rue Larrey	Angers
France	Service d'urologie, Groupe Hospitalier Pellegrin, place Amélie Raba Léon	Bordeaux
France	Service d'urologie - APHP Henri Mondor - 51, avenue du Maréchal de Lattre de Tassigny	Creteil
France	Service d'urologie - CHU de Limoges - 2, avenue Martin Luther King	Limoges
France	Service d'urologie - Hôpital de la Conception - 147 boulevard Baille	Marseille
France	Clinique Mutualiste Beausoleil	Montpellier
France	Service d'Urologie - APHP Hopital Cochin - 27, Rue du faubourg Saint Jacques	Paris
France	Service d'Urologie - APHP Hôpital Saint Louis - 1, avenue Claude-vellefaux	Paris
France	Service d'Urologie - Hospices Civls de Lyon - 165 chemin du grand Revoyet	Pierre Benite
France	Service d'urologie - CHRU Strasbourg - BP 426	Strasbourg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

References & Publications (20)

Barrack ER, Bujnovszky P, Walsh PC. Subcellular distribution of androgen receptors in human normal, benign hyperplastic, and malignant prostatic tissues: characterization of nuclear salt-resistant receptors. Cancer Res. 1983 Mar;43(3):1107-16. — View Citation

Boyle P, Gould AL, Roehrborn CG. Prostate volume predicts outcome of treatment of benign prostatic hyperplasia with finasteride: meta-analysis of randomized clinical trials. Urology. 1996 Sep;48(3):398-405. — View Citation

Chute CG, Stephenson WP, Guess HA, Lieber M. Benign prostatic hyperplasia: a population-based study. Eur Urol. 1991;20 Suppl 1:11-7. — View Citation

Colombel M, Vacherot F, Diez SG, Fontaine E, Buttyan R, Chopin D. Zonal variation of apoptosis and proliferation in the normal prostate and in benign prostatic hyperplasia. Br J Urol. 1998 Sep;82(3):380-5. — View Citation

Costa P, Ben Naoum K, Boukaram M, Wagner L, Louis JF. [Benign prostatic hyperplasia (BPH): prevalence in general practice and practical approach of French general practitioners. Results of a study based on 17,953 patients]. Prog Urol. 2004 Feb;14(1):33-9. French. — View Citation

Crawford ED, Wilson SS, McConnell JD, Slawin KM, Lieber MC, Smith JA, Meehan AG, Bautista OM, Noble WR, Kusek JW, Nyberg LM, Roehrborn CG; MTOPS RESEARCH Group. Baseline factors as predictors of clinical progression of benign prostatic hyperplasia in men treated with placebo. J Urol. 2006 Apr;175(4):1422-6; discussion 1426-7. — View Citation

Desgrandchamps F. [Combination therapy in benign prostatic hyperplasia (BPH)]. Ann Urol (Paris). 2004 Dec;38 Suppl 2:S24-8. Review. French. — View Citation

Frick J. [Pathophysiology of benign prostatic hyperplasia]. Wien Med Wochenschr. 1996;146(8):158-60. Review. German. — View Citation

Hieble JP, Boyce AJ, Caine M. Comparison of the alpha-adrenoceptor characteristics in human and canine prostate. Fed Proc. 1986 Oct;45(11):2609-14. — View Citation

Hieble JP, Ruffolo RR Jr. The use of alpha-adrenoceptor antagonists in the pharmacological management of benign prostatic hypertrophy: an overview. Pharmacol Res. 1996 Mar;33(3):145-60. Review. — View Citation

Isaacs JT, Coffey DS. Etiology and disease process of benign prostatic hyperplasia. Prostate Suppl. 1989;2:33-50. Review. — View Citation

Jacobsen SJ, Jacobson DJ, Girman CJ, Roberts RO, Rhodes T, Guess HA, Lieber MM. Treatment for benign prostatic hyperplasia among community dwelling men: the Olmsted County study of urinary symptoms and health status. J Urol. 1999 Oct;162(4):1301-6. — View Citation

Madersbacher S, Alivizatos G, Nordling J, Sanz CR, Emberton M, de la Rosette JJ. EAU 2004 guidelines on assessment, therapy and follow-up of men with lower urinary tract symptoms suggestive of benign prostatic obstruction (BPH guidelines). Eur Urol. 2004 Nov;46(5):547-54. — View Citation

Marcelli M, Shao TC, Li X, Yin H, Marani M, Denner L, Teng B, Cunningham GR. Induction of apoptosis in BPH stromal cells by adenoviral-mediated overexpression of caspase-7. J Urol. 2000 Aug;164(2):518-25. — View Citation

McConnell JD. The pathophysiology of benign prostatic hyperplasia. J Androl. 1991 Nov-Dec;12(6):356-63. Review. — View Citation

Radlmaier A, Eickenberg HU, Fletcher MS, Fourcade RO, Reis Santos JM, van Aubel OG, Bono AV. Estrogen reduction by aromatase inhibition for benign prostatic hyperplasia: results of a double-blind, placebo-controlled, randomized clinical trial using two doses of the aromatase-inhibitor atamestane. Atamestane Study Group. Prostate. 1996 Oct;29(4):199-208. — View Citation

Rhodes PR, Krogh RH, Bruskewitz RC. Impact of drug therapy on benign prostatic hyperplasia-specific quality of life. Urology. 1999 Jun;53(6):1090-8. Review. — View Citation

Wilt TJ, Ishani A, Rutks I, MacDonald R. Phytotherapy for benign prostatic hyperplasia. Public Health Nutr. 2000 Dec;3(4A):459-72. — View Citation

Wilt TJ, Ishani A, Stark G, MacDonald R, Lau J, Mulrow C. Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review. JAMA. 1998 Nov 11;280(18):1604-9. Erratum in: JAMA 1999 Feb 10;281(6):515. — View Citation

Zhu YS, Imperato-McGinley JL. 5alpha-reductase isozymes and androgen actions in the prostate. Ann N Y Acad Sci. 2009 Feb;1155:43-56. doi: 10.1111/j.1749-6632.2009.04115.x. Review. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of the patient with auto-questionnaire IPSS urinary symptomatology: questions 1 to 7 (0 to 35 score).		4 months
Secondary	IPSS question 8 (score 0 to 6)		18 months
Secondary	Uroflowmetry (Qmax in ml/s)		18 months
Secondary	• measure the post-voiding residue assessed by supra pubic ultrasound or urinary drainage		18 months
Secondary	measure of prostate volume assessed by endo-rectal ultrasound		18 months
Secondary	measurement of the erectile function by auto questionnaire IIEF-5 (0 to 24 score)		18 months
Secondary	urinary continence Evaluation by ICS 1 (0 to 23 score) and ICS 2 (0 to 12 score)		18 months
Secondary	bladder emptying mode (spontaneous or permanent probe)		18 months
Secondary	specific treatment for BPH (alpha blocking, 5 alpha reductase inhibitor and/or phytotherapy)		18 months
Secondary	Urinary retention		18 months
Secondary	Surgical treatment		18 months
Secondary	profile of gene and protein expression on the first urine flow after prostate massage		18 months