Hypothesis / Aims of Study
Urinary incontinence is common in women with an estimated prevalence of 500 Million world-wide, half of whom have stress urinary incontinence (SUI). Pelvic Floor Muscle Training (PFMT) is the standard of care for nonsurgical treatment of SUI with improvements reported in clinical measures including urine leak volume via pad weight (PW), voiding frequency and Quality of Life (QoL). Enhancements to improve the efficacy of PFMT are needed, especially in women who are not interested in or are not candidates for surgery. The aim of this study was to evaluate whether mechanotherapy (MT) applied to the pelvic floor muscles (PFM) in conjunction with standard PFMT improves continence in women with SUI.

This was a prospective, randomized, controlled, double-blinded, cross-over trial. The novel device used for this study (Flyte™, Pelvital, Inc., Minneapolis, MN, USA) is a vaginal device that provides 2-part MT: Part 1 MT - a carefully engineered probe that creates a preload on the pelvic floor muscles prior to muscle contraction. This pre-stress is expected to augment the effect of PFMT; and Part 2 MT - mechanical transduction with biofeedback which has been shown to provide incremental benefit in a previous study using the Flyte™ device. Subjects with SUI were randomized to an Intervention Arm (Part 1 and Part 2 MT + PFMT) versus a Control Arm (Part 1 MT only + PFMT). Subjects were asked to perform therapy daily for 5 minutes for 12 weeks. Endpoints were assessed at 6 and 12 weeks. The primary endpoint was 24-Hr PW determined at 6 weeks, at which time Control subjects were crossed over to the Intervention arm. There were multiple secondary endpoints, including PW at 12 weeks and Quality of life (QOL) assessed with the validated ICIQ-UI-SF.  QOL was assessed every 6 months thereafter for 24 months.

Data on 119 subjects were analyzed on an intent-to-treat basis.  Overall, compared to Baseline PW there was a median 59% relative improvement at 6 weeks (IQR, 18% to 79%) and median 68% relative improvement at 12 weeks (IQR, 43.5% to 87%; P<0.001). The absolute change was from a median pad weight of 27 g/24hr to 11.6 g/24hr at 6 weeks, and 6.4 g/24hr at 12 weeks (p<0.001) (Figure 1). There was no a significant difference in PW between study arms at either 6 or 12 weeks (at which time all subjects received MT Part 1 plus MT Part 2), although trends favored the Part 2 group that received mechanical transduction for the entire 12 weeks.  This was particularly evident in the final 34 subjects who received a study device with enhanced user biofeedback for stronger muscle contraction.  Furthermore, QOL measured by the Total ICIQ-UI-SF score improved significantly at both 6 and 12 weeks compared to Baseline (both p<0.001).  PW data was further stratified by Baseline PW severity level.  Statistically significant improvements were noted in the full study cohort in all severity levels at 6 and 12-weeks compared to Baseline, (Figure 2).  Mild and Moderate severity groups saw incremental improvement between Week 6 and Week 12, whereas Severe subjects saw a relative plateau. There were no significant differences between study arms, although a favorable trend was again noted in those receiving mechanical transduction.

Study subjects demonstrated significant reductions in 24-Hr pad weight and improved QOL using Flyte™ therapy. Of participants, 71% (81/114) achieved a clinically meaningful reduction (>50%) in pad weight by 12 weeks of therapy; with a 57% (68/119) having a >50% reduction in the first 6 weeks. Long term follow-up initially indicates that QOL benefits were generally sustained after the study ended. It was noted that some subjects responded exceptionally well with almost complete eradication of urine leakage while approximately 20% of women were non-responders. These observations occurred irrespective of incontinence severity level at baseline. The lack of response in some subjects suggests a possible condition requiring further clinical evaluation and potentially more aggressive treatment.  While a trend in incremental benefit of mechanical transduction was noted, the lack of significant difference in therapy response between study arms is presumed to be due to:  1) the greater than expected benefit from Part 1 MT muscle pre-stretch alone as an adjunct to PFMT; 2) the reduced amount of data from those subjects that received the updated patient interface.  As a result, the study was under powered to detect a significant difference between study arms at 6 weeks.

Flyte™ therapy with 2-part MT used as an adjunct to PFMT provided an effective, non-invasive therapeutic option in women with SUI as reflected by successful objective (PW) and subjective (QOL) outcomes. While trends towards incremental benefit of mechanical transduction (Part 2 MT) were observed at 6 weeks, the study was underpowered to evaluate for statistical significance.  Nevertheless, subjective QOL improvements appear to be sustained during long-term follow-up. Possible variables contributing to the differentiation of Flyte therapy responders versus non- responders warrants further investigation.