BACKGROUND: Among people with neurogenic bladder (NB), urinary tract infections (UTIs) are the most common cause of morbidity, emergency department visits, and rehospitalizations. As such, UTIs and the urinary symptoms that characterize them represent a significant burden among people with NB.

CONCLUSIONS: The USQNB-IC is a PC-PRO measure for monitoring of urinary symptoms among people with NB who use IC. In this first assessment of self-instilled intravesical LGG using the SMP-Pro approach in people with NB who use IC, intravesical LGG was safe and well-tolerated. Among adults, study results suggest that intravesical LGG may be effective at reducing urinary symptoms and does not alter bladder inflammation or bacterial load of the urine. There is preliminary evidence that intravesical LGG is safe to use in children with NB who use IC. Data are not sufficient to determine effectiveness in children.

LIMITATIONS: This was a first-in-human intervention trial of intravesical LGG for urinary symptoms, and as such, the scope and breadth of the study intervention and study population were strictly controlled. As this was not a randomized controlled study, definitive conclusions regarding effectiveness of the intervention are not possible to make. The results support continued research to expand the participant population and to further explore optimal dosing. Copyright © 2020. MedStar Health Research Institute. All Rights Reserved.

METHODS: (SA1) Using a patient-centered qualitative approach with over-the-phone focus groups and semistructured interviews, we developed the USQNB-IC. (SA2) Development of the SMP-Pro also used a blended patient-centered and evidence-based iterative approach. We then conducted an 18-month prospective single-arm quasi-experimental pre-post trial of the SMP-Pro (6 months each of urinary symptom observation: baseline, intervention, and washout) of self-management of urinary symptoms with intravesical Lactobacillus rhamnosus GG (LGG, Culturelle) using the USQNB-IC for weekly monitoring and the SMP-Pro during the intervention phase. (SA3) Safety (adverse events), tolerability, and effectiveness (trends of frequency, severity, and impact of symptoms) were analyzed over time in participants in the pre-post trial of SMP-Pro. Symptom burden and adverse events were primary outcomes. Secondarily, urine was collected in 26 participants to assess bladder inflammation and bacterial load.

OBJECTIVES: For specific aim 1 (SA1), we aimed to develop and validate a patient-centered, patient-reported outcome (PC-PRO) urinary symptom questionnaire for individuals with NB with intermittent catheterization (USQNB-IC) due to spinal cord injury, spina bifida, or multiple sclerosis. For SA2, we aimed to develop and pilot test a Self-management Protocol using Probiotics (SMP-Pro) to reduce the severity, frequency, and impact of urinary symptoms. For SA3, we aimed to estimate the strength of the associations between successful implementation of the SMP-Pro and urinary symptoms, bladder inflammation, and the urine microbiome.

RESULTS: For SA1, we enrolled 103 (96 adults, 7 children) participants. After completion of the alpha version of the USQNB-IC, 29 items resulted and were validated (face, content, divergent, and convergent validation) with a national sample of 581 people. In the pilot trial of SMP-Pro, "cloudy/foul-smelling urine" was identified as the best self-management trigger for the following reasons: (1) These symptoms are not considered indicative of a UTI according to evidence-based guidelines;, and (2) in our SA1 national sample, "cloudy" and "foul-smelling" urine were the 2 most commonly reported urinary symptoms (SA2). Using the validated USQNB-IC to monitor urinary symptoms and the SMP-Pro to guide intravesical LGG instillation, we found that 1 to 2 doses of intravesical LGG instilled within 30 hours in response to cloudy/foul-smelling urine (1) was safe and well-tolerated in our adults with NB who use IC; (2) reduced urinary symptom burden; and (3) did not alter bladder inflammation or bacterial load (SA3). Further, there is preliminary evidence of safety and tolerability in children.

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