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

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.

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.

Study Overview

• Status: Completed
• Conditions: Lower Urinary Tract Symptoms; Prostatic Hyperplasia
• Intervention / Treatment: Drug: Tadalafil; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Florence, Italy
    • Clinica Urologica - Azienda Ospedaliero-Universitaria Careggi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tadalafil; 43 male subjects affected by BPH (benign prostatic hyperplasia) planned for simple prostatectomy will be randomized to tadalafil 5 mg - 1 film-coated tablet orally once daily for 12 weeks.	Drug: Tadalafil; Tadalafil 5 mg once daily for 12 weeks.; Other Names: Cialis
Placebo Comparator: Placebo; 43 male subjects affected by BPH (benign prostatic hyperplasia) planned for simple prostatectomy will be randomized to placebo.	Other: Placebo; Placebo tablet once daily for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Volumetric change of the prostate	Prostate volume as assessed by transrectal ultrasound	12 weeks
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
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
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
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
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
Improvement in erectile function	Erectile function will be assessed by using the International Index of Erectile Function-5 (IIEF-5) score.	12 weeks

Collaborators and Investigators

• Sponsor: University of Florence
• Collaborators: Eli Lilly and Company

Publications and helpful links

General Publications

• 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 alpha-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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): January 1, 2019
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: September 22, 2014
• First Submitted That Met QC Criteria: September 25, 2014
• First Posted (Estimate): September 30, 2014

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Phosphodiesterase 5 Inhibitors; BPH/LUTS
• Additional Relevant MeSH Terms: Pathologic Processes; Urological Manifestations; Prostatic Diseases; Prostatic Hyperplasia; Hyperplasia; Lower Urinary Tract Symptoms; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Tadalafil
• Other Study ID Numbers: ANDRO-AOUC-2014-01