Variability in Methodology of Erectile Dysfunction Regenerative Therapy Trials on ClinicalTrials.gov.

OBJECTIVE: To evaluate the variability in the criteria of erectile dysfunction (ED) regenerative therapy trials registered on ClinicalTrials.gov. METHODS: Interventional trials on ClinicalTrials.gov with the keywords "erectile dysfunction" and variations of "shockwave," "platelet rich plasma," "stem cell," "regenerative," and "restorative" were examined. Inclusion/exclusion criteria and primary/secondary outcomes were compared between extracorporeal shockwave therapy (ESWT), platelet rich plasma and stem cell injections (PRP/SC), and other regenerative therapies (ORT) groups. RESULTS: Of the 92 trials analyzed, International Index of Erectile Function (IIEF) score was the most common primary outcome (72%), with a higher prevalence in ESWT trials than PRP/SC or ORT trials (89% vs 44% and 58%, P <.001). Safety/tolerability was a primary outcome for 44% of PRP/SC trials and 25% of ORT trials but no ESWT trials (P <.001). ESWT trials more frequently had sexual/romantic relationship-based inclusion criteria and cancer treatment-related exclusion criteria than PRP/SC and ORT trials. CONCLUSION: There is substantial variability in the inclusion/exclusion criteria and outcome measures among ED regenerative therapy trials. ESWT trials most frequently utilized IIEF and had the strictest inclusion/exclusion criteria, suggesting more rigorous and functional outcome-based studies. Conversely, PRP/SC and ORT trials, but not ESWT trials, had safety/tolerability as a primary outcome, likely due to the experimental nature of these therapies. The variability in inclusion/exclusion criteria and outcome measures limits comparison of the various ED regenerative therapies.

Deep Phenotyping the Anterior Urethral Stricture: Characterizing the Relationship Between Inflammation, Fibrosis, Patient History, and Disease Pathophysiology.

PURPOSE: Anterior urethral stricture disease (aUSD) is a complex, heterogeneous condition that is idiopathic in origin for most men. This gap in knowledge rarely affects the current management strategy for aUSD, as urethroplasty does not generally consider etiology. However, as we transition towards personalized, minimally invasive treatments for aUSD and begin to consider aUSD prevention strategies, disease pathophysiology will become increasingly important. The purpose of this study was to perform a deep phenotype of men undergoing anterior urethroplasty for aUSD. We hypothesized that unique biologic signatures and potential targets for intervention would emerge based on stricture presence/absence, stricture etiology, and the presence/absence of stricture inflammation. MATERIALS AND METHODS: Men with aUSD undergoing urethroplasty were recruited from one of 5 participating centers. Enrollees provided urethral stricture tissue and blood/serum on the day of surgery and completed patient-reported outcome measure questionnaires both pre- and postoperatively. The initial study had 3 aims: (1) to determine pediatric and adult subacute and repeated perineal trauma (SRPT) exposures using a study-specific SRPT questionnaire, (2) to determine the degree of inflammation and fibrosis in aUSD and peri-aUSD (normal urethra) tissue, and (3) to determine levels of systemic inflammatory and fibrotic cytokines. Two controls groups provided serum (normal vasectomy patients) and urethral tissue (autopsy patients). Cohorts were based on the presence/absence of stricture, by presumed stricture etiology (idiopathic, traumatic/iatrogenic, lichen sclerosus [LS]), and by the presence/absence of stricture inflammation. RESULTS: Of 138 enrolled men (120 tissue/serum; 18 stricture tissue only), 78 had idiopathic strictures, 33 had trauma-related strictures, and 27 had LS-related strictures. BMI, stricture length, and stricture location significantly differed between cohorts (P < .001 for each). The highest BMIs and the longest strictures were observed in the LS cohort. SRPT exposures did not significantly differ between etiology cohorts, with > 60% of each reporting low/mild risk. Stricture inflammation significantly differed between cohorts, with mild to severe inflammation present in 27% of trauma-related strictures, 54% of idiopathic strictures, and 48% of LS strictures (P = .036). Stricture fibrosis did not significantly differ between cohorts (P = .7). Three serum cytokines were significantly higher in patients with strictures compared to stricture-free controls: interleukin-9 (IL-9; P = .001), platelet-derived growth factor-BB (P = .004), and CCL5 (P = .01). No differences were observed in the levels of these cytokines based on stricture etiology. However, IL-9 levels were significantly higher in patients with inflamed strictures than in patients with strictures lacking inflammation (P = .019). Degree of stricture inflammation positively correlated with serum levels of IL-9 (Spearman's rho 0.224, P = .014). CONCLUSIONS: The most common aUSD etiology is idiopathic. Though convention has implicated SRPT as causative for idiopathic strictures, here we found that patients with idiopathic strictures had low SRPT rates that were similar to rates in patients with a known stricture etiology. Stricture and stricture-adjacent inflammation in idiopathic stricture were similar to LS strictures, suggesting shared pathophysiologic mechanisms. IL-9, platelet-derived growth factor-BB, and CCL5, which were elevated in patients with strictures, have been implicated in fibrotic conditions elsewhere in the body. Further work will be required to determine if this shared biologic signature represents a potential mechanism for an aUSD predisposition.