A-botulinic Toxin for Symptomatic Benign Prostate Hypertrophy

NCT01275521 | Completed Phase 3

• 1 other identifier: CHUBX 2010/39
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 11

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

Outcome Measures

Primary Outcomes (1)

• Evaluation of the patient with auto-questionnaire IPSS urinary symptomatology: questions 1 to 7 (0 to 35 score).

  4 months

Secondary Outcomes (11)

• IPSS question 8 (score 0 to 6)

  18 months

• Uroflowmetry (Qmax in ml/s)

  18 months

• • measure the post-voiding residue assessed by supra pubic ultrasound or urinary drainage

  18 months

• measure of prostate volume assessed by endo-rectal ultrasound

  18 months

• measurement of the erectile function by auto questionnaire IIEF-5 (0 to 24 score)

  18 months

Study Arms (2)

BONT-A intra-prostatic injection

EXPERIMENTAL

Drug: BONT-A intra-prostatic injection

optimized medical BPH treatment

ACTIVE COMPARATOR

Drug: Optimized medical BPH treatment

Interventions

BONT-A intra-prostatic injection 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;

BONT-A intra-prostatic injection

Optimized medical BPH treatment DRUG

Optimization of the medical therapy according to recent guidelines

optimized medical BPH treatment

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Subject affiliate or beneficiary of a social protection

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (11)

Service d'Urologie - CH du Pays d'Aix - Avenue de Tamaris

Aix-en-Provence, 13616, France

Location

Service d'Urologie, CHU d'Angers 4, rue Larrey

Angers, 49933, France

Location

Service d'urologie, Groupe Hospitalier Pellegrin, place Amélie Raba Léon

Bordeaux, 33076, France

Location

Service d'urologie - APHP Henri Mondor - 51, avenue du Maréchal de Lattre de Tassigny

Créteil, 94000, France

Location

Service d'urologie - CHU de Limoges - 2, avenue Martin Luther King

Limoges, 87052, France

Location

Service d'urologie - Hôpital de la Conception - 147 boulevard Baille

Marseille, 13005, France

Location

Clinique Mutualiste Beausoleil

Montpellier, 33070, France

Location

Service d'Urologie - APHP Hopital Cochin - 27, Rue du faubourg Saint Jacques

Paris, 75014, France

Location

Service d'Urologie - APHP Hôpital Saint Louis - 1, avenue Claude-vellefaux

Paris, 75475, France

Location

Service d'Urologie - Hospices Civls de Lyon - 165 chemin du grand Revoyet

Pierre-Bénite, 69495, France

Location

Service d'urologie - CHRU Strasbourg - BP 426

Strasbourg, 67091, France

Location

Related Publications (21)

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  PMID: 15098749 BACKGROUND

• 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.

  PMID: 10367833 BACKGROUND

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

  PMID: 2482772 BACKGROUND

• 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.

  PMID: 1722154 BACKGROUND

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

  PMID: 1722791 BACKGROUND

• 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.

  PMID: 6186370 BACKGROUND

• 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.

  PMID: 10893637 BACKGROUND

• 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.

  PMID: 9772874 BACKGROUND

• 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.

  PMID: 8876703 BACKGROUND

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

  PMID: 8767399 BACKGROUND

• 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.

  PMID: 2428671 BACKGROUND

• 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.

  PMID: 8880886 BACKGROUND

• 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.

  PMID: 15474261 BACKGROUND

• 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.

  PMID: 11276294 BACKGROUND

• 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.

  PMID: 9820264 BACKGROUND

• 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.

  PMID: 19250191 BACKGROUND

• 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.

  PMID: 16516013 BACKGROUND

• 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.

  PMID: 8804493 BACKGROUND

• 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.

  PMID: 15651487 BACKGROUND

• 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.

  PMID: 10492184 BACKGROUND

• 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.

  PMID: 29383480 DERIVED

MeSH Terms

Conditions

Prostatic Hyperplasia

Condition Hierarchy (Ancestors)

Prostatic Diseases; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Grégoire ROBERT, MD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

• Antoine BENARD, MD

  University Hospital, Bordeaux

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2011
• First Posted: January 12, 2011
• Study Start: January 10, 2011
• Primary Completion: April 28, 2015
• Study Completion: April 28, 2015
• Last Updated: August 23, 2017

Record last verified: 2017-08

Locations

FR (11)