Prostatic HyperplasiaPhase 3PROTOXNCT01275521
A-botulinic Toxin for Symptomatic Benign Prostate Hypertrophy
A Phase 3 study testing BONT-A intra-prostatic injection and Optimized medical BPH treatment in people with Prostatic Hyperplasia, run by University Hospital, Bordeaux at 11 sites in France.
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. Read more about this study
- Who is it for?
- Ages 50 to 85 years, men only
- Conditions the study is for
- Prostatic Hyperplasia
- What is being tested?
- BONT-A intra-prostatic injection and Optimized medical BPH treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 127 participants
- Where
- 11 sitesFrance
- Study dates
- 10 Jan 2011to 28 Apr 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
France11 sites
Service d'Urologie - CH du Pays d'Aix - Avenue de Tamaris
Aix-en-Provence, 13616
Service d'Urologie, CHU d'Angers 4, rue Larrey
Angers, 49933
Service d'urologie, Groupe Hospitalier Pellegrin, place Amélie Raba Léon
Bordeaux, 33076
Service d'urologie - APHP Henri Mondor - 51, avenue du Maréchal de Lattre de Tassigny
Créteil, 94000
Service d'urologie - CHU de Limoges - 2, avenue Martin Luther King
Limoges, 87052
Service d'urologie - Hôpital de la Conception - 147 boulevard Baille
Marseille, 13005
Clinique Mutualiste Beausoleil
Montpellier, 33070
Service d'Urologie - APHP Hopital Cochin - 27, Rue du faubourg Saint Jacques
Paris, 75014
Service d'Urologie - APHP Hôpital Saint Louis - 1, avenue Claude-vellefaux
Paris, 75475
Service d'Urologie - Hospices Civls de Lyon - 165 chemin du grand Revoyet
Pierre-Bénite, 69495
Service d'urologie - CHRU Strasbourg - BP 426
Strasbourg, 67091
About this study
Official title: Study of the Effectiveness and the Tolerance of Intraprostatic A-botulinic Toxin Injection, in the Treatment of Symptomatic Benign Prostate Hypertrophy.
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
- Being tested
- BONT-A intra-prostatic injection, Optimized medical BPH treatment
- Medical subject headings
- Prostatic Hyperplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BONT-A intra-prostatic injectionDrug
- 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 treatmentDrug
Optimization of the medical therapy according to recent guidelines
| Study group | Role | What they receive |
|---|---|---|
| BONT-A intra-prostatic injection | Experimental | Not described Receives: Drug: BONT-A intra-prostatic injection |
| optimized medical BPH treatment | Active comparator | Not described Receives: Drug: Optimized medical BPH treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the patient with auto-questionnaire IPSS urinary symptomatology: questions 1 to 7 (0 to 35 score).
Measured: 4 months
Secondary outcomes (11)
IPSS question 8 (score 0 to 6)
Measured: 18 months
Uroflowmetry (Qmax in ml/s)
Measured: 18 months
• measure the post-voiding residue assessed by supra pubic ultrasound or urinary drainage
Measured: 18 months
measure of prostate volume assessed by endo-rectal ultrasound
Measured: 18 months
measurement of the erectile function by auto questionnaire IIEF-5 (0 to 24 score)
Measured: 18 months
urinary continence Evaluation by ICS 1 (0 to 23 score) and ICS 2 (0 to 12 score)
Measured: 18 months
bladder emptying mode (spontaneous or permanent probe)
Measured: 18 months
specific treatment for BPH (alpha blocking, 5 alpha reductase inhibitor and/or phytotherapy)
Measured: 18 months
Urinary retention
Measured: 18 months
Surgical treatment
Measured: 18 months
profile of gene and protein expression on the first urine flow after prostate massage
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2011 (estimated)
- Study start10 Jan 2011
- Primary completion28 Apr 2015
- Study completion28 Apr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Prostatic HyperplasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Grégoire ROBERT, MD, Principal investigator, University Hospital, BordeauxAntoine BENARD, MD, Study chair, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01275521
- Sponsor's protocol ID
- CHUBX 2010/39
- Acronym
- PROTOX
- Status last verified
- Aug 2017
- First submitted
- 11 Jan 2011
- Last updated
- 23 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 15098749Rhodes 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.
PubMed 10367833Isaacs JT, Coffey DS. Etiology and disease process of benign prostatic hyperplasia. Prostate Suppl. 1989;2:33-50. doi: 10.1002/pros.2990150506.
PubMed 2482772Chute 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.
PubMed 1722154McConnell JD. The pathophysiology of benign prostatic hyperplasia. J Androl. 1991 Nov-Dec;12(6):356-63.
PubMed 1722791Barrack 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.
PubMed 6186370Marcelli 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.
PubMed 10893637Colombel 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.
PubMed 9772874Radlmaier 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.
PubMed 8876703Frick J. [Pathophysiology of benign prostatic hyperplasia]. Wien Med Wochenschr. 1996;146(8):158-60. German.
PubMed 8767399Hieble JP, Boyce AJ, Caine M. Comparison of the alpha-adrenoceptor characteristics in human and canine prostate. Fed Proc. 1986 Oct;45(11):2609-14.
PubMed 2428671Hieble 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.
PubMed 8880886Madersbacher 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.
PubMed 15474261Wilt 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.
PubMed 11276294Wilt 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.
PubMed 9820264
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Effectiveness and the Tolerance of Intraprostatic A-botulinic Toxin Injection, in the Treatment of Symptomatic Benign Prostate Hypertrophy.
- ClinicalTrials.gov ID
- NCT01275521
- Acronym / sponsor ID
- PROTOX / CHUBX 2010/39
- Conditions
- Prostatic Hyperplasia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- 10 Jan 2011 (actual)
- Primary completion
- 28 Apr 2015 (actual)
- Study completion
- 28 Apr 2015 (actual)
- First posted
- 12 Jan 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BONT-A intra-prostatic injection | Experimental | Drug: BONT-A intra-prostatic injection |
| optimized medical BPH treatment | Active comparator | Drug: Optimized medical BPH treatment |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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);
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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; | Drug | BONT-A intra-prostatic injection |
| Optimized medical BPH treatmentOptimization of the medical therapy according to recent guidelines | Drug | optimized medical BPH treatment |
Primary outcome
Evaluation of the patient with auto-questionnaire IPSS urinary symptomatology: questions 1 to 7 (0 to 35 score).
Time frame: 4 months
11 secondary outcomes
IPSS question 8 (score 0 to 6)
Time frame: 18 months
Uroflowmetry (Qmax in ml/s)
Time frame: 18 months
• measure the post-voiding residue assessed by supra pubic ultrasound or urinary drainage
Time frame: 18 months
measure of prostate volume assessed by endo-rectal ultrasound
Time frame: 18 months
measurement of the erectile function by auto questionnaire IIEF-5 (0 to 24 score)
Time frame: 18 months
urinary continence Evaluation by ICS 1 (0 to 23 score) and ICS 2 (0 to 12 score)
Time frame: 18 months
bladder emptying mode (spontaneous or permanent probe)
Time frame: 18 months
specific treatment for BPH (alpha blocking, 5 alpha reductase inhibitor and/or phytotherapy)
Time frame: 18 months
Urinary retention
Time frame: 18 months
Surgical treatment
Time frame: 18 months
profile of gene and protein expression on the first urine flow after prostate massage
Time frame: 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2017.
- Background: PubMed 15098749Costa 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.
- Background: PubMed 10367833Rhodes 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.
- Background: PubMed 2482772Isaacs JT, Coffey DS. Etiology and disease process of benign prostatic hyperplasia. Prostate Suppl. 1989;2:33-50. doi: 10.1002/pros.2990150506.
- Background: PubMed 1722154Chute 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.
- Background: PubMed 1722791McConnell JD. The pathophysiology of benign prostatic hyperplasia. J Androl. 1991 Nov-Dec;12(6):356-63.
- Background: PubMed 6186370Barrack 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.
- Background: PubMed 10893637Marcelli 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.
- Background: PubMed 9772874Colombel 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.
- Background: PubMed 8876703Radlmaier 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.
- Background: PubMed 8767399Frick J. [Pathophysiology of benign prostatic hyperplasia]. Wien Med Wochenschr. 1996;146(8):158-60. German.
- Background: PubMed 2428671Hieble JP, Boyce AJ, Caine M. Comparison of the alpha-adrenoceptor characteristics in human and canine prostate. Fed Proc. 1986 Oct;45(11):2609-14.
- Background: PubMed 8880886Hieble 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Grégoire ROBERT, MD principal investigator
University Hospital, Bordeaux
Antoine BENARD, MD study chair
University Hospital, Bordeaux
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BONT-A intra-prostatic injection and Optimized medical BPH treatment in people with Prostatic Hyperplasia, run by University Hospital, Bordeaux at 11 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of the patient with auto-questionnaire IPSS urinary symptomatology: questions 1 to 7 (0 to 35 score). (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01275521, which also lists 21 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2017.