Intravesical Lactobacillus to Reduce Urinary Symptoms After Spinal Cord Injury

Study Overview
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Brief Summary
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The objectives of the proposed research among this population are: 1) to define clinically meaningful change (i.e. differentiating states of health and illness) with respect to urinary symptoms, urine inflammation, cultivable bacteria, and the urine ecosystem; and 2) to determine the optimal intravesical Lactobacillus RhamnosusGG (LGG®) dose to be used to reduce urinary symptoms in a future clinical trial.

Detailed Description
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Urinary tract infection (UTI) is the most common outpatient infection world-wide, and for people with spinal cord injury (SCI) and neurogenic bladder (NB), it is the most common infection, secondary condition, cause for emergency room visits, and infectious cause of hospitalization. Despite its prevalence, attempts to ameliorate UTI among people with SCI are stymied by long-standing diagnostic challenges which arise from evidence gaps around gold standard diagnostic tests (urinalysis and urine culture) that have lower sensitivity and specificity for UTI in this population. A high prevalence of chronic inflammation leading to persistence of white blood cells (WBC) in the urine confounds the utility of WBC count, pyuria, and leukocyte esterase as biomarkers for UTI; nitrites in urine indicate the presence of only specific (but not all) organisms, many of which are present to a greater extent in the urine of people with SCI; and people with SCI have a high prevalence of asymptomatic bacteriuria. These physiologic changes render the gold standard diagnostic tests less useful for identifying UTI in persons with SCI. SPECIFIC AIM 1 2 urine samples (sampling at least 2 weeks apart) for urinalysis, urine culture, uNGAL, and NGS (16S rRNA and shotgun) under the same conditions. In addition to completing the USQNB-IC prior to urine collection, participants will complete the USQNB-IC 3 days after urine collection SPECIFIC AIM 2 Intravesical LGG dose (group: high or low) will be obtained, USQNB-IC, urine collection for urinalysis, culture, NGAL and next generation sequencing as described above. And patient satisfaction questions.

Official Title
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Intravesical Lactobacillus to Reduce Urinary Symptoms After Spinal Cord Injury

Conditions
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Spinal Cord Injuries, Neurogenic Bladder

Intervention / Treatment
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* Drug: Culturelle 10 Billion CFU Capsule (2 doses)
* Drug: Culturelle 10 Billion CFU Capsule (4 doses)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: SCI at least 1-year duration; Neurogenic bladder; Utilizing intermittent catheterization for bladder management; Women must be premenopausal and not currently menstruating; Community dwelling Exclusion Criteria: Use of prophylactic antibiotics; Instillation of intravesical antimicrobials to prevent UTI; Psychologic or psychiatric conditions influencing the ability to follow instructions; Use of oral or IV antibiotics within the past 2 weeks; Sexual activity within the previous 72 hours; Participation in another study with which results could be confounded.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Design: Prospective, randomized pilot intervention clinical trial. Target Enrollment: 182 subjects total at least 1-year post-SCI. Setting: National sample (N=114 intervention only, no urine collection) and local Washington, DC metropolitan area (N=68 intervention + urine collection). Controls: This is a 2-arm dose-finding pilot clinical trial, as such there is no control group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dosage Group<br>For the LGG® instillation, participants will be instructed to mix the contents of 1 LGG capsule into 45 cc sterile 0.9% saline. After mixing, participants will draw up the 45cc liquid LGG mixture into a 60cc syringe and instill via the intermitent catheter. Participants will receive 2 LGG capsules and will repeat this process the following day (Low dose). Subjects will remain in the study for up to 29 months, with participation ending after one completed intervention (2 doses) and post-intervention assessments are complete. If urinary symptoms do not occur warranting instillation during the ensuing 29 months, participants will be asked to return any remaining kits (including LGG®). Participants will be instructed to complete the USQNB-IDC weekly until study completion. | Drug: Culturelle 10 Billion CFU Capsule (2 doses)<br>* For the LGG instillation, participants will be instructed to mix the contents of 1 LGG capsule into saline. After mixing, participants will draw up the liquid LGG mixture into a syringe and instill via the intermittent catheter after the last catheterization prior to going to bed. Participants will receive 2 LGG capsules and will repeat this process the following night (Low dose). Subjects will remain in the study for up to 29 months, with participation ending after one completed intervention (2 doses) and post-intervention assessments are complete. If urinary symptoms do not occur warranting instillation during the ensuing 29 months, participants will be asked to return any remaining capsules<br>* Other names: Lactobacillus RhamnosusGG;|
| Experimental: High Dosage Group<br>For the LGG® instillation, participants will be instructed to mix the contents of 1 LGG capsule into 45 cc sterile 0.9% saline. After mixing, participants will draw up the 45cc liquid LGG mixture into a 60cc syringe and instill via the intermittent catheter. Participants will receive 4 LGG capsules and will repeat this process the following day twice for a total of four doses (High dose). Subjects will remain in the study for up to 29 months, with participation ending after one completed intervention (4 doses) and post-intervention assessments are complete. If urinary symptoms do not occur warranting instillation during the ensuing 29 months, participants will be asked to return any remaining kits (including LGG®). Participants will be instructed to complete the USQNB-IDC weekly until study completion. | Drug: Culturelle 10 Billion CFU Capsule (4 doses)<br>* For the LGG instillation, participants will be instructed to mix the contents of 1 LGG capsule into saline. After mixing, participants will draw up the liquid LGG mixture into a syringe and instill via the intermittent catheter after the last catheterization prior to going to bed. Participants will receive 4 LGG capsules and will repeat this process twice daily for a total of four doses (High dose). Subjects will remain in the study for up to 29 months, with participation ending after one completed intervention (4 doses) and post-intervention assessments are complete. If urinary symptoms do not occur warranting instillation during the ensuing 29 months, participants will be asked to return any remaining capsules<br>* Other names: Lactobacillus RhamnosusGG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter | Will measure change in urinary symptoms for those that use an intermittent catheter. Higher scores may mean worse outcomes. | (SA1) day of urine collection | 
| Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter | Will measure change in urinary symptoms for those that use an intermittent catheter. Higher scores may mean worse outcomes. | (SA1) day 1 post urine collection | 
| Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter | Will measure change in urinary symptoms for those that use an intermittent catheter. Higher scores may mean worse outcomes. | (SA1) day 2 post urine collection | 
| Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter | Will measure change in urinary symptoms for those that use an intermittent catheter. Higher scores may mean worse outcomes. | (SA1) day 3 post urine collection | 
| Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter | Will measure change in urinary symptoms for those that use an intermittent catheter. Higher scores may mean worse outcomes. | (SA2) Weekly up to 29 months | 
| Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter | Will measure change in urinary symptoms for those that use an intermittent catheter. Higher scores may mean worse outcomes. | (SA2) day 1 of intervention | 
| Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter | Will measure change in urinary symptoms for those that use an intermittent catheter. Higher scores may mean worse outcomes. | (SA2) 24-48 hours after intervention completion | 
| Change in Urine white blood cell count | urinalysis | (SA1) day 1 post urine collection | 
| Change in Urine white blood cell count | urinalysis | (SA1) day 14 post urine collection | 
| Change in Urine white blood cell count | urinalysis | (SA 2) day 1 of intervention | 
| Change in Urine white blood cell count | urinalysis | (SA 2) 24-48 hours after intervention completion | 
| Change in Urine Nitrite | urinalysis | (SA1)day 1 post urine collection | 
| Change in Urine Nitrite | urinalysis | (SA1)day 14 post urine collection | 
| Change in Urine Nitrite | urinalysis | (SA 2) day 1 of intervention | 
| Change in Urine Nitrite | urinalysis | (SA 2) 24-48 hours after intervention completion | 
| Change in Urine NGAL | Urine NGAL | (SA1)day 1 post urine collection | 
| Change in Urine NGAL | Urine NGAL | (SA1)day 14 post urine collection | 
| Change in Urine NGAL | Urine NGAL | (SA 2) day 1 of intervention | 
| Change in Urine NGAL | Urine NGAL | (SA 2) 24-48 hours after intervention completion | 
| Change in Cultivable Bacteria | urine culture | (SA1)day 1 post urine collection | 
| Change in Cultivable Bacteria | urine culture | (SA1)day 14 post urine collection | 
| Change in Cultivable Bacteria | urine culture | (SA 2) day 1 of intervention | 
| Change in Cultivable Bacteria | urine culture | (SA 2) 24-48 hours after intervention completion | 
| Change in Urine microbiome composition | proportion of different bacterial species | (SA1)day 1 post urine collection | 
| Change in Urine microbiome composition | proportion of different bacterial species | (SA1)day 14 post urine collection | 
| Change in Urine microbiome composition | proportion of different bacterial species | (SA 2) day 1 of intervention | 
| Change in Urine microbiome composition | proportion of different bacterial species | (SA 2) 24-48 hours after intervention completion | 
| International SCI Lower Urinary Tract Function Basic Data Set | A tool to describe urinary tract impairment, awareness of need to empty the bladder, main bladder emptying method, medications used for bladder management, surgeries, and change in urinary symptoms in the past year. Score is not associated with outcome | Day 1 | 
| International SCI Core Data Set | Includes date of injury, dates of initial hospitalization admission and discharge, neurological data. Score is not associated with outcomes | Day 1 | 
| NINDS Medical History CDE: | A brief medical history using body system categories. Score is not associated with outcomes | Day 1 | 
| NINDS Prior and Concomitant Medications CDE | Contains whether or not the participant is taking a medication during the study protocol, name of medication, reason for medication, medication dose, frequency, start and end dates, and free text. Score is not associated with outcomes | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intermittent Catheter