Clinical study on inflammation related biomarkers in patients treated for LUTS related to BPH: a prospective, double-blind, randomised study comparing hexanic LSESr (Permixon) with Tamsulosin

INTRODUCTION & OBJECTIVES: Chronic prostatic inflammation is a molecular pathway involved in the development and progression of Benign Prostatic Hyperplasia (BPH). Recent in vitro studies confirmed anti‐inflammatory effects of the hexanic Lipidosterolic Extract of Serenoa repens (LSESr, Permixon). The primary endpoint of this exploratory study was to assess the effects of LSESr and Tamsulosin LP on inflammation related biomarkers in patients suffering lower urinary tract symptoms (LUTS) related to BPH. MATERIAL & METHODS: This prospective multicentre randomized study assessed the expression of inflammation biomarkers in two parallel groups. After a 28‐days washout period, 206 patients who met inclusion criteria including presence of LUTS for over 12 months, IPSS score > 12, prostate volume > 30cm3, 5 < Qmax < 15ml/s, were randomized to receive either LSESr hard capsule 160 mg b.i.d or Tamsulosin 0.4 mg o.a.d for 90 days. Urinary biomarkers and clinical data were assessed at randomization and at follow‐up visits (D30 and D90) in double‐blind conditions. Urine samples were collected after digital rectal examination: 29 commonly reported inflammatory markers were analyzed by quantitative PCR; protein transcripts were quantified by ELISA test. RESULTS: Out of 29 selected genes, 15 were expressed in a significant number of urinary samples. At D90 results for 9 genes were in favour of LSESr (down‐regulation and/or less up‐regulation) for 3 in favour of Tamsulosin and for 3 unchanged. Out of the gene‐transcripts selected, 3 proteins were detected in urinary samples (CCL2/MCP‐1, CXCL10 and MIF). At D90, CCL2 and CXCL10 were completely abolished at a higher rate in the LSESr group (27.4% and 20.5%) than Tamsulosin group (15.5% and 12.7%) and arose at a lower frequency in the LSESr group (8.2% and 9.6%) than Tamsulosin group (16.9% and 15.5%). Moreover MIF expression was significantly reduced by LSESr compared to Tamsulosin (p=0.007; down‐regulated in 42.5% of LSESr vs 23.9% of Tamsulosin). Furthermore, contrary to Tamsulosin, in patients who over expressed one of the following genes at baseline CXCL10, CCL2, PTPRC, PTGS2 and treated by LSESr, we observed at D90 a better response to IPSS compared to those who did not over expressed these genes (e.g for CXCL10: median of IPSS change from baseline ‐7.0 vs ‐4.0 respectively). CONCLUSIONS: This prospective clinical study showed for the first time in man the anti‐inflammatory activity of hexanic LSESr confirming previous in vitro results. In comparison to Tamsulosin, it was able to reduce urinary detection of key chemo‐attractants for human monocytes/macrophages and T cells, the most frequently observed cell type in BPH inflammation nodules.