Is there an effect of oral anticholinergics on the clinical and molecular parameters of prostate and bladder of patients with benign prostatic hyperplasia and overactive bladder?

• Register: ISRCTN
• Last refreshed on: 11 February 2019
• Main ID: ISRCTN11552705
• Date of registration: 18/04/2017
• Prospective Registration: No
• Primary sponsor: Aristotele University of Thessaloniki
• Public title: Is there an effect of oral anticholinergics on the clinical and molecular parameters of prostate and bladder of patients with benign prostatic hyperplasia and overactive bladder?
• Scientific title: Changes in lower urinary tract cholinergic pathways in patients with Benign Prostatic Hyperplasis-associated Lower Urinary Tract Symptoms and Overactive Bladder symptoms: The effect of oral antimuscarinics
• Date of first enrolment: 01/10/2013
• Target sample size: 105
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN11552705
• Study type: Interventional
• Study design: Prospective multi-centre open-label active comparator randomised controlled study (Other)
• Phase: Not Applicable

Countries of recruitment

Greece

Contacts

• Name: Vasileios Sakalis

Key inclusion & exclusion criteria

Inclusion criteria:
Treatment arms (Group 1 and 2):
1. Treatment-naïve men
2. Age 50 years or older
3. Predominantly storage LUTS as defined by the IPSS (storage subscore = voiding subscore and score = 3 in the urgency question) and at least 3 urgency episodes per 24h as documented in a 3-day bladder diary
4. Prostate volume =30ml
5. Maximum flow rate (Qmax) =10ml/s
6. Post-void residual (PVR)=100ml
7. PSA value = 4 ng/ml. Patients with positive DRE and/or PSA values 4-10ng/ml are included only after negative prostate biopsy.

Control group 1:
1. Treatment-naïve men
2. Age 50 years or older
3. Predominantly storage LUTS as defined by the IPSS (storage subscore = voiding subscore and score = 3 in the urgency question) and at least 3 urgency episodes per 24h as documented in a 3-day bladder diary
4. Prostate volume = 30ml
5. Maximum flow rate (Qmax) = 10ml/s
6. Post-void residual (PVR) = 100ml
7. PSA = 4ng/ml. Patients with positive DRE and/or PSA values 4-10bng/ml are included only after negative prostate biopsy
8. Consent to provide prostate or bladder tissue

Control group 2 and 3: Asymptomatic men
1. Treatment-naïve men
2. Age 50 years or older
3. Total IPSS <7 and/or a score of 0-1 in the IPSS ‘urgency’ question.
4. Prostate volume = 30ml
5. Maximum flow rate (Qmax) = 10ml/s
6. Post-void residual (PVR) = 100ml
7. PSA = 4ng/ml. Patients with positive DRE and/or PSA values 4-10 ng/ml were included only after negative prostate biopsy.

Exclusion criteria:
1. Patients with neurogenic lower urinary tract dysfunction
2. Patients with a history of urinary tract malignancy
3. Any contraindication to the use of a-blockers or antimuscarinics
4. Metabolic conditions that may affect lower urinary tract (LUT) function
5. Psychiatric illnesses
6. Chronic kidney, hepatic or cardiac failure
7. History of urinary stone disease
8. History of urethral instrumentation
9. Urethral stricture
10. Acute urinary tract infection (UTI) or history of recurrent UTI’s
11. Use of medications known to affect LUT function including PDE-5 inhibitors
12. Positive urine culture
13. Microscopic haematuria, proteinuria or glucosuria. Subjects with pyuria were included only after a negative urine culture.


Age minimum:
Age maximum:
Gender: Male

Health Condition(s) or Problem(s) studied

Benign prostatic hyperplasia, Overactive Bladder
Urological and Genital Diseases
Benign prostatic hyperplasia, Overactive Bladder

Intervention(s)

This study involves two study arms, one clinical and one molecular.

Arm 1: Clinical
Potential participants are identified during an assessment in the male Lower Urinary Tract Symptoms (LUTS) clinic. They are given a study information pack and asked to return a three-day bladder dairy within two weeks. Those who documented the required number of daily urgent episodes are asked to join the study. Participants are randomly allocated using SPSS software (1:1) into one of two groups.

Group 1 Tamsulosin monotherapy: Participants receive tamsulosin 0.4mg tamsulosin once at night (Tamsulosin OCAS 0.4mg, Astellas) for six months.

Group 2 Tamsulosin & Solifenacin Combination therapy: Participants receive solifenacin 5mg plus tamsulosin 0.4mg to take once at night (Astellas) for six months.

Titration of solifenacin dose (10mg) is possible in the combination therapy patients who have inadequate symptom control after 4 weeks. Patients are followed up at baseline and at 26 weeks to assess their urinary symptoms, quality of life and to complete tests including transrectal and transabdominal ultrasonography, free uroflowmetry and pressure-flow study, basic biochemistry, PSA and Testosterone blood tests. At week 26 they are asked to repeat a bladder diary. Participants have interim follow-up assessments at four and 12 weeks that include questionnaires, uroflowmetry and transabdominal ultrasonography. At study completion participants are asked whether they would like to continue on medical therapy or undergo prostatectomy (transurethral resection, for prostates <80mls or open procedure, for prostates>80mls). If they choose the prostactectomy they are included in the second arm of the study.

Arm 2: Molecular
This arm compares tissue samples from different symptomatic patients. Participants in this group include those from the first arm of the study who

Primary Outcome(s)

Muscarinic receptor expression is measured using the immunohistochemistry (Western Blot and RT-PCR) at 6 months

Secondary Outcome(s)

1. Urinary symptoms are measured using IPSS Questionnaire at three and six months
2. Storage ability is measured using IPSS Questionnaire Storage subscale at three and six months
3. Amount of prostate specific antigen (PSA) in the blood is measured using standard laboratory biochemistry tests at three and six months
4. Semen parameters are measured using standard laboratory biochemistry tests at three and six months
5. Total prostate and adenoma volume is measured using Transabdominal and transrectal ultrasonography at three and six months
6. Quality of life is measured using the QoL question of the IPSS at three and six months
7. Adrenergic receptor expression in prostate and bladder is measured using immunohistochemistry (Western Blot and RT-PCR) at six months
8. Sensory receptor TRPV1 expression is measured using immunohistochemistry (Western Blot and RT-PCR) at six months
9. eNOS and VEGF expression in prostate and bladder using immunohistochemistry (Western Blot and RT-PCR) at six months

Secondary ID(s)

71/13.03.2014

Source(s) of Monetary Support

European Social Fund, Greece National Resources

Ethics review

Status:
Approval date:
Contact:

Aristotele University of Thessaloniki, Greece, School of Medicine, Ethics Committee, 13/03/2014, ref: 71/13.03.2014

Results

• Results available: Yes
• Date Completed: 30/06/2015