A-botulinic Toxin for Symptomatic Benign Prostate Hypertrophy - Full Text View

Purpose

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.

Condition	Intervention	Phase
Prostatic Hyperplasia	Drug: BONT-A intra-prostatic injection Drug: Optimized medical BPH treatment	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Study of the Effectiveness and the Tolerance of Intraprostatic A-botulinic Toxin Injection, in the Treatment of Symptomatic Benign Prostate Hypertrophy.

Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:

Evaluation of the patient with auto-questionnaire IPSS urinary symptomatology: questions 1 to 7 (0 to 35 score). [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

IPSS question 8 (score 0 to 6) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
Uroflowmetry (Qmax in ml/s) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
• measure the post-voiding residue assessed by supra pubic ultrasound or urinary drainage [ Time Frame: 18 months ] [ Designated as safety issue: No ]
measure of prostate volume assessed by endo-rectal ultrasound [ Time Frame: 18 months ] [ Designated as safety issue: No ]
measurement of the erectile function by auto questionnaire IIEF-5 (0 to 24 score) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
urinary continence Evaluation by ICS 1 (0 to 23 score) and ICS 2 (0 to 12 score) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
bladder emptying mode (spontaneous or permanent probe) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
specific treatment for BPH (alpha blocking, 5 alpha reductase inhibitor and/or phytotherapy) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
Urinary retention [ Time Frame: 18 months ] [ Designated as safety issue: No ]
Surgical treatment [ Time Frame: 18 months ] [ Designated as safety issue: No ]
profile of gene and protein expression on the first urine flow after prostate massage [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	226
Study Start Date:	January 2011
Estimated Study Completion Date:	July 2015
Estimated Primary Completion Date:	July 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: BONT-A intra-prostatic injection	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;
Active Comparator: optimized medical BPH treatment	Drug: Optimized medical BPH treatment Optimization of the medical therapy according to recent guidelines

Eligibility

Ages Eligible for Study:	50 Years to 85 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01275521

Contacts

Contact: Grégoire ROBERT, MD	(33) - 05 56 79 55 47	gregroire.robert@chu-bordeaux.fr
Contact: Philippe BALLANGER, Professor		philippe.ballanger@chu-bordeaux.fr

Locations

France
Service d'Urologie - CH du Pays d'Aix - Avenue de Tamaris	Recruiting
AIX-en-PROVENCE, France, 13616
Principal Investigator: Marc FOURMARIER, MD
Service d'Urologie, CHU d'Angers 4, rue Larrey	Recruiting
Angers, France, 49933
Principal Investigator: Abdel-Rahmene AZZOUZI, MD
Service d'urologie, Groupe Hospitalier Pellegrin, place Amélie Raba Léon	Recruiting
Bordeaux, France, 33076
Contact: Grégoire ROBERT, MD (33) 05 56 79 55 47 gregoire.robert@chu-bordeaux.fr
Principal Investigator: Grégoire ROBERT, MD
Sub-Investigator: Philippe BALLANGER, Professor
Service d'urologie - APHP Henri Mondor - 51, avenue du Maréchal de Lattre de Tassigny	Recruiting
Creteil, France, 94000
Principal Investigator: Alexandre de la TAILLE, Professor
Service d'urologie - CHU de Limoges - 2, avenue Martin Luther King	Recruiting
Limoges, France, 87052
Principal Investigator: Aurélien DESCAZEAUD, MD
Service d'urologie - Hôpital de la Conception - 147 boulevard Baille	Recruiting
Marseille, France, 13005
Principal Investigator: Gilles KARSENTY, MD
Sub-Investigator: Véronique DELAPORTE, MD
Clinique Mutualiste Beausoleil	Not yet recruiting
Montpellier, France, 33070
Contact: Xavier REBILLARD, MD
Principal Investigator: Xavier REBILLARD, MD
Sub-Investigator: Antoine FAIX, MD
Service d'Urologie - APHP Hôpital Saint Louis - 1, avenue Claude-vellefaux	Recruiting
Paris, France, 75475
Principal Investigator: François DESGRANDCHAMPS, Professor
Sub-Investigator: Paul Joseph MERIA, MD
Service d'Urologie - APHP Hopital Cochin - 27, Rue du faubourg Saint Jacques	Not yet recruiting
Paris, France, 75014
Principal Investigator: Nicolas BARRY DELONGCHAMPS, MD
Service d'Urologie - Hospices Civls de Lyon - 165 chemin du grand Revoyet	Recruiting
Pierre Benite, France, 69495
Sub-Investigator: Marian DEVONEC, Professor
Service d'urologie - CHRU Strasbourg - BP 426	Recruiting
Strasbourg, France, 67091
Principal Investigator: Christian SAUSSINE, Professor

Sponsors and Collaborators

University Hospital, Bordeaux

Investigators

Principal Investigator:	Grégoire ROBERT, MD	University Hospital, Bordeaux
Study Chair:	Antoine BENARD, MD	University Hospital, Bordeaux

More Information

Publications:

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.

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.

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

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

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

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.

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.

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.

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.

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

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.

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.

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.

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

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.

Zhu YS, Imperato-McGinley JL. 5alpha-reductase isozymes and androgen actions in the prostate. Ann N Y Acad Sci. 2009 Feb;1155:43-56. Review.

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.

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.

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

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.

Responsible Party:	University Hospital, Bordeaux
ClinicalTrials.gov Identifier:	NCT01275521 History of Changes
Other Study ID Numbers:	CHUBX 2010/39
Study First Received:	January 11, 2011
Last Updated:	April 24, 2013
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:

Prostatic Hyperplasia
Hyperplasia
Hypertrophy
Prostatic Diseases

Genital Diseases, Male
Pathologic Processes
Pathological Conditions, Anatomical

ClinicalTrials.gov processed this record on May 16, 2013

A-botulinic Toxin for Symptomatic Benign Prostate Hypertrophy (PROTOX)