Effect of 12 Weeks Treatment With Tadalafil vs Placebo on Lower Urinary Tract Symptoms

Lower Urinary Tract Symptoms Clinical Trial

Official title:

Double-blind, Placebo-controlled Study on Men With Lower Urinary Tract Symptoms to Assess Changes in Pressure Flow Study and in Molecular Profile of Prostatic Tissue After 12 Weeks Treatment With Tadalafil.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02252367
• Other study ID #: ANDRO-AOUC-2014-01
• Status: Completed
• Phase: Phase 4
• Start date: December 2015
• Est. completion date: June 2020

Study information

• Verified date: April 2021
• Source: University of Florence
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

At present time several preclinical and clinical study have demonstrated the safety and efficacy of PDE5 (phosphodiesterase type 5)-inhibitors for LUTS/BPH (lower urinary tract symptoms/benign prostatic hyperplasia) patients with or without erectile dysfunction. However, the link between clinical outcomes (symptoms scores), functional activity (urodynamic findings) and molecular pathways, in particular regarding inflammatory pattern (molecular analyses), has not been previously investigated. Aim of present study is to assess, for the first time in literature, changes in pressure flow study (PFS) and changes in molecular profile of prostatic tissue (inflammatory and tissue remodeling markers) in men treated for 12 weeks with tadalafil 5 mg compared with placebo and to correlate these data with changes in symptoms scores (IPSS, International Prostatic Symptoms Score) in men with LUTS secondary to BPH refractory to alpha blockers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: June 2020
• Est. primary completion date: January 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• adult male subjects planned to undergo simple prostatectomy (TURP, Transurethral resection of the prostate, or open prostatectomy) for benign prostatic hyperplasia;
• treatment with alpha-blockers (Tamsulosin 0.4 mg/die)
• being capable of giving informed consent.

Exclusion Criteria:

• participation in another clinical study;
• known or suspected presence of prostatic cancer or PSA (prostate specific antigen) value >10 ng/mL;
• suspected lack of the participant's compliance;
• known severe allergies or hypersensitivity to the study drug (active substance or excipients of the formulation);
• nown neurogenic bladder (i.e. Parkinson's disease);
• suspected or proven urinary infections;
• presence of bladder stone.

Related Conditions & MeSH terms

• Hyperplasia
• Lower Urinary Tract Symptoms
• Prostatic Hyperplasia

Intervention

Drug:
• Tadalafil
Tadalafil 5 mg once daily for 12 weeks.

Other:
• Placebo
Placebo tablet once daily for 12 weeks.

Locations

Country	Name	City	State
Italy	Clinica Urologica - Azienda Ospedaliero-Universitaria Careggi	Florence

Sponsors (2)

Lead Sponsor	Collaborator
University of Florence	Eli Lilly and Company

Country where clinical trial is conducted

Italy, 

References & Publications (2)

Gacci M, Corona G, Salvi M, Vignozzi L, McVary KT, Kaplan SA, Roehrborn CG, Serni S, Mirone V, Carini M, Maggi M. A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with a-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol. 2012 May;61(5):994-1003. doi: 10.1016/j.eururo.2012.02.033. Epub 2012 Feb 25. Review. — View Citation

Gacci M, Vittori G, Tosi N, Siena G, Rossetti MA, Lapini A, Vignozzi L, Serni S, Maggi M, Carini M. A randomized, placebo-controlled study to assess safety and efficacy of vardenafil 10 mg and tamsulosin 0.4 mg vs. tamsulosin 0.4 mg alone in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Sex Med. 2012 Jun;9(6):1624-33. doi: 10.1111/j.1743-6109.2012.02718.x. Epub 2012 Apr 17. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement of LUTS/BPH symptoms	BPH-associated inflammatory symptoms will be assessed by using the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI). BPH-associated LUTS will be assessed by using International Prostate Symptom Score (IPSS).	12 weeks
Secondary	Improvement of pressure flow study (PFS) parameters	Maximum flow rate (Qmax), average flow rate (Qave), voided volume (Vcomp), post void residual volume (PVR) will be evaluated. An abdominal ultrasound immediately after voiding for uroflowmetry will be performed in order to determine the PVR.	12 weeks
Secondary	Volumetric change of the prostate	Prostate volume as assessed by transrectal ultrasound	12 weeks
Secondary	Change in prostate inhomogeneity and in the number of prostatic macrocalcifications	BPH-associated prostate inhomogeneity and presence of micro-calcifications will be assessed by using male genital tract male genital tract colour-Doppler ultrasonography.	12 weeks
Secondary	Variation in genic expression of prostatic inflammation markers	BPH-associated prostate inflammation, fibrosis, and hypoxia will be measured by immunohistochemical and quantitative RT-PCR (qRT-PCR) analyses of inflammatory-, fibrosis- and hypoxia-related markers.	12 weeks
Secondary	Variation in serum inflammation markers CRP (C-reactive protein) and ESR (Erythrocyte Sedimentation Rate)	CRP measured on serum and ESR measured on blood drawn at baseline and after 12 weeks	12 weeks
Secondary	Improvement in metabolic profile	Metabolic parameters will be evaluated (glycaemia, insulinemia, total cholesterol, HDL, triglycerides, HbA1c, mean arterial pressure, waist circumference, body mass index)	12 weeks
Secondary	Variation in seminal plasma IL-8 (interleukin-8) levels	Seminal IL-8, a chemokine involved in male genital tract infection/inflammation, will be evaluated.	12 weeks
Secondary	Improvement in erectile function	Erectile function will be assessed by using the International Index of Erectile Function-5 (IIEF-5) score.	12 weeks