Intravesical Lactobacillus to Reduce Urinary Symptoms After Spinal Cord Injury

Phase 2

Completed

• Conditions: Spinal Cord Injuries; Neurogenic Bladder
• Interventions: Drug: Culturelle 10 Billion CFU Capsule (2 doses); Drug: Culturelle 10 Billion CFU Capsule (4 doses)

• Registration Number: NCT04373512
• Lead Sponsor: Medstar Health Research Institute

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-11-01
• Study First Submitted QC: 2020-04-30
• Study First Posted: 2020-05-04
• Study Start: 2020-05-20
• Primary Completion: 2025-02-14
• Study Completion: 2025-02-14
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-07
• Last Update Posted: 2025-05-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 182

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low Dosage Group	Culturelle 10 Billion CFU Capsule (2 doses)	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 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.
High Dosage Group	Culturelle 10 Billion CFU Capsule (4 doses)	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.

Primary Outcome Measures

Name	Time	Method
Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter	(SA2) 24-48 hours after intervention completion	Will measure change in urinary symptoms for those that use an intermittent catheter. Higher scores may mean worse outcomes.
Change in Cultivable Bacteria	(SA 2) 24-48 hours after intervention completion	urine culture
Change in Urine white blood cell count	(SA 2) 24-48 hours after intervention completion	urinalysis
NINDS Medical History CDE:	Day 1	A brief medical history using body system categories. Score is not associated with outcomes
NINDS Prior and Concomitant Medications CDE	Day 1	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
Change in Urine Nitrite	(SA 2) 24-48 hours after intervention completion	urinalysis
Change in Urine NGAL	(SA 2) 24-48 hours after intervention completion	Urine NGAL
International SCI Lower Urinary Tract Function Basic Data Set	Day 1	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
International SCI Core Data Set	Day 1	Includes date of injury, dates of initial hospitalization admission and discharge, neurological data. Score is not associated with outcomes
Change in Urine microbiome composition	(SA 2) 24-48 hours after intervention completion	proportion of different bacterial species

Trial Locations

Locations (1)

MedStar National Rehabilitation Hospital; 🇺🇸 Washington, District of Columbia, United States