Impact of Probiotics on Urinary Symptoms in Spinal Cord Injury SCI and SB

Study Overview
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Brief Summary
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As a collaborative effort between MedStar National Rehabilitation Hospital (NRH)/MedStar Health Research Institute (MHRI), Children's National Medical Center (CNMC) Department of Urology, Children's Research Institute (CRI) Center for Genetic Medicine Research, and Georgetown University Medical Center, the overall objective of this study is to develop, validate, and assess a patient-initiated, probiotics-based, self management protocol that is initiated at the time of urinary symptoms. The self-management protocol will allow patients to manage urinary symptoms and avoid potentially unnecessary antibiotic use, and provide a readily-available means of maintaining health, function, and independence throughout the lifespan.

Detailed Description
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Lower urinary symptoms are a common issue for individuals with neurogenic bladder, commonly occurring in the Spina bifida and Spinal Cord Injury population. In this study, probiotics will be introduced into the bladder to prevent UTIs. Introduction of probiotics will be determined by a validated symptom questionnaire (USQ-NB) and protocol (SMP-PRO). This study will estimate the strength of the associations between successful implementation of the probiotic self-management program (USQ-NB and SMP-PRO) and urinary symptoms, bladder inflammation, and the urine microbiome. Investigators will conduct an 18-month study in which each participant will serve as his/her own control through 3 phases of study: 6-months usual care (baseline), 6-months probiotic intervention, and 6-months follow-up. Participants will complete the Urinary Symptom Questionnaire weekly. After 6 months of baseline data collection, participants will receive the Lactobacillus (Culturelle GG, 20 billion live organisms for adults and 10 billion live organisms for children <18 years of age), will be instructed on preparation and intravesicular instillation of the Lactobacillus, and will have a tutorial with a fellow consumer on use of the patient-initiated protocol. The protocol and Lactobacillus bladder instillation instructions (including a step-by-step video) will be available on the study website for 24/7 access and written instructions will be provided at the time of instruction. For the intravesicular Lactobacillus instillation, participants will be instructed to mix the contents into sterile saline. After mixing, participants will draw up the liquid Lactobacillus mixture into a 60cc catheter tip syringe and instill via the intermittent catheter after fully emptying the bladder. Participants will be instructed not to catheterize for at least 4 hours after the bladder instillation. Participants will receive 10 Culturelle GG at the beginning of the treatment phase. At the end of each month, the coordinator or RA will ask how many remaining tablets the participant has, and if needed dispense the next supply of 10 tablets. Participants will be instructed to complete the USQ-NB weekly. If/when urinary symptoms occur, subjects will be instructed to follow the protocol to determine whether to initiate intravesicular Lactobacillus instillation or be evaluated by a physician. The self-management protocol will also direct them to discontinue Lactobacillus instillation or be evaluated by a physician if symptoms remit, persist (after 2 instillations), or worsen. The maximum number of instillations is 2 over 28 hours. If participants are directed by the self-management protocol to seek medical attention or s/he feels the need for medical evaluation, s/he will be advised to obtain care as they typically would by their health care provider. Participants will be supplied with letters to be brought to their health care provider notifying them of the study and requesting sharing of urinalysis and urine culture results with the research team. A verified UTI will include those that resulted in antibiotic treatment by a health care professional. An additional urine sample for metagenomics will either be left with the health care provider for pick up by the research team, brought to the research site, or obtained by the RA at a mutually convenient site. After completion of the 6-month patient-initiated, self-management protocol intervention period, participants will monitor symptoms weekly using the USQ-NB for the final 6-month phase of the 18-month study.

Official Title
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The Impact of Self-Management With Probiotics on Urinary Symptoms and the Urine Microbiome in Individuals With Spinal Cord Injury (SCI) and Spina Bifida (SB)

Conditions
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Lower Urinary Tract Symptoms

Intervention / Treatment
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* Drug: Lactobacillus rhamnosus GG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥18 years SCI, SB or MS at least 1-year duration Neuropathic bladder, as determined by the attending physician Utilizing intermittent catheterization for bladder management A history of 2 or more UTIs in the past year Community dwelling. Exclusion Criteria: Known genitourinary pathology beyond neuropathic bladder (i.e., vesicoureteral reflux, bladder or kidney stones, etc.) Use of prophylactic antibiotics Instillation of intravesicular agents to reduce UTI (i.e., gentamycin) Psychologic or psychiatric conditions influencing the ability to follow instructions Participation in another study in which results would be confounded Pregnant or breastfeeding Individuals with a history of acquired or genetic immunodeficiencies; active, acute or chronic serious infections (i.g., viral hepatitides, HIV/AIDs) Individuals with cancer/autoimmune disorders Serious allergy to any component or excipients in the live bacterial combination product No change in neurologic status in the previous 2 weeks Taken antibiotic for any reason in the previous 2 weeks Any patient with history of sensitivity or allergy to ampicillin or tetracycline Current urinary tract infection or urinary tract infection within the previous 2 weeks (as defined by Infectious Diseases Society of America CAUTI Guidelines, 2010).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adults with Spinal Cord Injury<br>Lactobacillus rhamnosus GG | Drug: Lactobacillus rhamnosus GG<br>* For the intravesicular Lactobacillus instillation, participants will be instructed to mix the contents of 1 Lactobacillus capsule into 45 cc sterile 0.9% saline.5,6 After mixing, participants will draw up the 45 cc of the liquid Lactobacillus mixture into a 60cc catheter tip syringe and instill via the intermittent catheter after the last catheterization prior to going to bed. Participants will receive 10 Lactobacillus GG tabs at the beginning of treatment phase. At the end of each month, the coordinator or RA will ask how many remaining tablets the participant has, and if needed dispense the next supply of 10 tablets Participants will be instructed to complete the USQ-NB weekly.<br>* Other names: Culturelle;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lactobacillus Safety | Total Adverse Events (AE + Serious AE) per participant . | months 1-18 of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lactobacillus Tolerability | This is a one-item satisfaction rating. While thinking only about the preceding 6-month time period: can you estimate, using a scale from 0 to 100%, whether or not you would seek out this intervention and pay for it yourself if insurance did not pay for it? Participants indicated their answer by moving a slider with three anchors: 0%=Would absolutely never do this; 50%=Might do this; 100%= Would absolutely do this. If a participant is less satisfied, their rating will be lower, and if they are more satisfied, the rating would be higher, but the item did not have options for better or worse. This is not a published scale, we included this item in our general data collection. Ratings averaged over final 12 months of study (Satisfaction question was answered by study participants at 3 time points; 6 months, 12 months and 18 months) | Months 7-18 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spina Bifida, Spinal Cord Injury, Lower Urinary Tract Symptoms, Probiotics, Intermittent Catheterization