A-botulinic Toxin for Symptomatic Benign Prostate Hypertrophy

NCT ID: NCT01275521

Last Updated: 2017-08-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-10
• Study Completion Date: 2015-04-28

Brief 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.

Conditions

Prostatic Hyperplasia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BONT-A intra-prostatic injection

Group Type: EXPERIMENTAL

BONT-A intra-prostatic injection

Intervention Type: DRUG

• 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

Group Type: ACTIVE_COMPARATOR

Optimized medical BPH treatment

Intervention Type: DRUG

Optimization of the medical therapy according to recent guidelines

Interventions

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;

Intervention Type: DRUG

Optimized medical BPH treatment

Optimization of the medical therapy according to recent guidelines

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Bordeaux

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Grégoire ROBERT, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bordeaux

Antoine BENARD, MD

Role: STUDY_CHAIR

University Hospital, Bordeaux

Locations

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

Créteil, , 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-Bénite, , France

Service d'urologie - CHRU Strasbourg - BP 426

Strasbourg, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 15098749 (View on PubMed)

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. doi: 10.1016/s0090-4295(99)00041-2.

Reference Type: BACKGROUND

PMID: 10367833 (View on PubMed)

Isaacs JT, Coffey DS. Etiology and disease process of benign prostatic hyperplasia. Prostate Suppl. 1989;2:33-50. doi: 10.1002/pros.2990150506.

Reference Type: BACKGROUND

PMID: 2482772 (View on PubMed)

Chute CG, Stephenson WP, Guess HA, Lieber M. Benign prostatic hyperplasia: a population-based study. Eur Urol. 1991;20 Suppl 1:11-7. doi: 10.1159/000471739.

Reference Type: BACKGROUND

PMID: 1722154 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 1722791 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 6186370 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10893637 (View on PubMed)

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. doi: 10.1046/j.1464-410x.1998.00752.x.

Reference Type: BACKGROUND

PMID: 9772874 (View on PubMed)

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. doi: 10.1002/(SICI)1097-0045(199610)29:43.0.CO;2-7.

Reference Type: BACKGROUND

PMID: 8876703 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 8767399 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 2428671 (View on PubMed)

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. doi: 10.1006/phrs.1996.0022.

Reference Type: BACKGROUND

PMID: 8880886 (View on PubMed)

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. doi: 10.1016/j.eururo.2004.07.016.

Reference Type: BACKGROUND

PMID: 15474261 (View on PubMed)

Wilt TJ, Ishani A, Rutks I, MacDonald R. Phytotherapy for benign prostatic hyperplasia. Public Health Nutr. 2000 Dec;3(4A):459-72. doi: 10.1017/s1368980000000549.

Reference Type: BACKGROUND

PMID: 11276294 (View on PubMed)

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. doi: 10.1001/jama.280.18.1604.

Reference Type: BACKGROUND

PMID: 9820264 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19250191 (View on PubMed)

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. doi: 10.1016/S0022-5347(05)00708-1.

Reference Type: BACKGROUND

PMID: 16516013 (View on PubMed)

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. doi: 10.1016/s0090-4295(96)00353-6.

Reference Type: BACKGROUND

PMID: 8804493 (View on PubMed)

Desgrandchamps F. [Combination therapy in benign prostatic hyperplasia (BPH)]. Ann Urol (Paris). 2004 Dec;38 Suppl 2:S24-8. doi: 10.1016/s0003-4401(04)80003-2. French.

Reference Type: BACKGROUND

PMID: 15651487 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10492184 (View on PubMed)

Robert G, Descazeaud A, Karsenty G, Saussine C, Azzouzi AR, de la Taille A, Desgrandchamps F, Faix A, Fourmarier M, Georget A, Benard A, Barry Delongchamps N. Prostatic injection of botulinum toxin is not inferior to optimized medical therapy in the management of lower urinary tract symptoms due to benign prostatic hyperplasia: results of a randomized clinical trial. World J Urol. 2018 Jun;36(6):921-929. doi: 10.1007/s00345-018-2193-y. Epub 2018 Jan 30.

Reference Type: DERIVED

PMID: 29383480 (View on PubMed)

Other Identifiers

CHUBX 2010/39

Identifier Type: -

Identifier Source: org_study_id