Intravesicle Lactobacillus to Reduce Urinary Symptoms After Spinal Cord Injury .
Abstract
Objective: This proposal specifically focuses on the population of people with SCI and neurogenic bladder who manage their bladders with intermittent catheterization (IC). The objectives of this study are to: (1) define clinically meaningful change (i.e., differentiating states of health and illness) with respect to urinary symptoms, urine inflammation, and the urinary tracts microbial ecosystem; (2) determine the optimal intravesical LactobacillusGG® (LGG®) dose to reduce urinary symptoms for use in a future clinical trial; and (3) advance diagnosis, self-management, and clinical research around urinary symptoms in SCI by developing a method for doing research that leverages computational methods, but focuses on integrating the patients report of symptoms with gold standard (urinalysis and urine culture) and novel (urine NGAL and sequencing) clinical data to reliably detect changes from normal that are clinically meaningful and interpretable-both within and across people. Applicability: The short-term applicability of this work directly and immediately includes advancing: (1) self-management of symptoms with intravesical LGG; and (2) diagnostics through differentiation of asymptomatic bacteriuria from urinary tract infection through use of uNGAL. The long-term applicability of this work includes advancing (3) prevention of UTI with LGG; and (4) reduction in over-prescription of antibiotics and resistant microbes. Impact on Persons with SCI: This work specifically targets people with SCI who use intermittent catheters (due to neurogenic bladder). These individuals will potentially be helped by having an easily accessible method to reduce, through self-management, frequent and burdensome urinary symptoms, reducing the occurrence of UTI and ultimately, antimicrobial resistance due to overuse of antimicrobials. Pilot Clinical Trial: The pilot clinical trial proposed in this project is a dose-finding experiment to determine whether Low (2 doses in 24 hours) or High (4 doses in 48 hours) dose self-instilled intravesical LGG is superior, and which dose should therefore be used in a next-step clinical trial. Project Timeline: To achieve a person-related outcome, we anticipate that it may take: (1) an additional 3 to 5 years beyond the completion of this trial to conduct the clinical trial to determine the efficacy of intravesical LGG; (2) an additional 2 to 5 years for confirmatory assessment of uNGAL as a useful clinical marker, together with other outcomes we will study; and (3) an additional 3 to 5 years for definitive and reproducible testing of diagnostics models developed in this study. Of note, since LGG is readily available (and does not require a physicians prescription) and this work represents a new use of this product (requiring an amendment to our existing Investigational New Drug approval from the Food and Drug Administration), once this study is completed, it will be available for immediate use by the SCI population for urinary symptoms while the efficacy clinical trial is ongoing. Contributions of the Proposed Research to Advancing the Field, Patient Care and/or Quality of Life: Urinary tract infection is the most common outpatient infection world-wide, and for people with SCI, it is the most common infection, secondary condition, cause for emergency room visits, and infectious cause of hospitalization. Attempts to reduce UTI among people with SCI are stymied by long-standing diagnostic challenges that arise from evidence gaps around gold standard diagnostic tests (urinalysis and urine culture) that have lower sensitivity and specificity for UTI in SCI. A recent study of nearly 400 Veterans revealed that 87% had asymptomatic bacteriuria, and of these, 36% were treated with antibiotics unnecessarily. Further, we have demonstrated in our pilot work that all of the people (in a national sample) who reported a history of UTIs had experienced at least one or more of 29 possible symptoms attribut
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910541
Entities
People
- Suzanne Groah
Organizations
- MedStar Health Research Institute
- United States Army