Intravesical Lactobacillus for Urinary Symptoms Among People With NLUTD Who Use Indwelling Catheters

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.

Study Overview

• Status: Recruiting
• Conditions: Neurogenic Bladder
• Intervention / Treatment: Drug: Culturelle 10 Billion CFU Capsule

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.

SA1. Estimate healthy, asymptomatic state variability of urine NGAL (uNGAL), white blood cells (uWBC), nitrite, cultivable bacteria, and the urinary microbiome.

SA2. Estimate the effect of intravesical LGG dose on urinary symptoms (primary outcome), uNGAL, uWBC, nitrites, cultivable bacteria, and the urine microbiome (secondary outcomes).

• Study Type: Interventional
• Enrollment (Anticipated): 182
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amanda K Rounds, PhD; Phone Number: 202-877-1591; Email: Amanda.K.Rounds@medstar.net
• Study Contact Backup: Name: Inger H Ljungberg; Phone Number: 202-877-1694; Email: Inger.H.Ljungberg@medstar.net

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • MedStar National Rehabilitation Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Neurogenic bladder for at least 6 months;
• Utilizing indwelling catheterization for bladder management;
• Women must be premenopausal and not currently menstruating;
• Community dwelling
• physical disability

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Low Dosage; 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 indwelling catheter (the catheter will not be changed as this would represent 2 interventions). Participants will be instructed the plug their catheter for 1 hour. 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; LGG® (Culturelle Probiotic with Lactobacillus RhamnosusGG, shown to produce the largest amount of antibacterial substances against pathogenic bacteria) will be used. 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 indwelling catheter (the catheter will not be changed as this would represent 2 interventions). Participants will be instructed the plug their catheter for 1 hour. Participants will receive 2 or 4 LGG capsules (depending on randomization group) and will repeat this process the following day ("Low" dose) or twice daily for a total of four doses ("High" dose) according to randomization group.; Other Names: Lactobacillus Rhamnosus GG
ACTIVE_COMPARATOR: High dosage; 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 indwelling catheter (the catheter will not be changed as this would represent 2 interventions). Participants will be instructed the plug their catheter for 1 hour. 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; LGG® (Culturelle Probiotic with Lactobacillus RhamnosusGG, shown to produce the largest amount of antibacterial substances against pathogenic bacteria) will be used. 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 indwelling catheter (the catheter will not be changed as this would represent 2 interventions). Participants will be instructed the plug their catheter for 1 hour. Participants will receive 2 or 4 LGG capsules (depending on randomization group) and will repeat this process the following day ("Low" dose) or twice daily for a total of four doses ("High" dose) according to randomization group.; Other Names: Lactobacillus Rhamnosus GG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary Symptom Questionnaire for Neurogenic Bladder- Indwelling catheter	Will measure change in urinary symptoms for those that use an indwelling catheter. Higher score may mean worse outcomes. (local urine collection participants only)	(SA 1) day of urine collection
Urinary Symptom Questionnaire for Neurogenic Bladder- Indwelling catheter	Will measure change in urinary symptoms for those that use an indwelling catheter. Higher score may mean worse outcomes. (local urine collection participants only)	(SA 1) day 1 post urine collection
Urinary Symptom Questionnaire for Neurogenic Bladder- Indwelling catheter	Will measure change in urinary symptoms for those that use an indwelling catheter. Higher score may mean worse outcomes. (local urine collection participants only)	(SA 1) day 2 post urine collection
Urinary Symptom Questionnaire for Neurogenic Bladder- Indwelling catheter	Will measure change in urinary symptoms for those that use an indwelling catheter. Higher score may mean worse outcomes. (local urine collection participants only)	(SA 1) day 3 post urine collection
Urinary Symptom Questionnaire for Neurogenic Bladder- Indwelling catheter	Will measure change in urinary symptoms for those that use an indwelling catheter. Higher score may mean worse outcomes	(SA 2) Weekly up to 29 months
Urinary Symptom Questionnaire for Neurogenic Bladder- Indwelling catheter	Will measure change in urinary symptoms for those that use an indwelling catheter. Higher score may mean worse outcomes. (local urine collection participants only)	(SA 2) day 1 of intervention (low or high dose)
Urinary Symptom Questionnaire for Neurogenic Bladder- Indwelling catheter	Will measure change in urinary symptoms for those that use an indwelling catheter. Higher score may mean worse outcomes	(SA 2) day 2 of intervention (low or high dose)
Urinary Symptom Questionnaire for Neurogenic Bladder- Indwelling catheter	Will measure change in urinary symptoms for those that use an indwelling catheter. Higher score may mean worse outcomes	(SA 2) day 3 of intervention (low or high dose)
Urinary Symptom Questionnaire for Neurogenic Bladder- Indwelling catheter	Will measure change in urinary symptoms for those that use an indwelling catheter. Higher score may mean worse outcomes	(SA 2) day 4 of intervention (low or high dose)
Urinary Symptom Questionnaire for Neurogenic Bladder- Indwelling catheter	Will measure change in urinary symptoms for those that use an indwelling catheter. Higher score may mean worse outcomes	(SA 2) day 5 of intervention (high dose only)
Urinary Symptom Questionnaire for Neurogenic Bladder- Indwelling catheter	Will measure change in urinary symptoms for those that use an indwelling catheter. Higher score may mean worse outcomes. (local urine collection participants only)	(SA 2) 24-48 hours after intervention completion
Change in Urine white blood cell count	urinalysis. (local urine collection participants only)	(SA 1) day 1 post urine collection
Change in Urine white blood cell count	urinalysis. (local urine collection participants only)	(SA 1) day 14 post urine collection
Change in Urine white blood cell count	urinalysis. (local urine collection participants only)	(SA 2) day 1 of intervention
Change in Urine white blood cell count	urinalysis. (local urine collection participants only)	(SA 2) 24-48 hours after intervention completion
Change in Urine Nitrite	urinalysis. (local urine collection participants only)	(SA 1) day 1 post urine collection
Change in Urine Nitrite	urinalysis. (local urine collection participants only)	(SA 1) day 14 post urine collection
Change in Urine Nitrite	urinalysis. (local urine collection participants only)	(SA 2) day 1 of intervention
Change in Urine Nitrite	urinalysis. (local urine collection participants only)	(SA 2) 24-48 hours after intervention completion
Change in Urine NGAL	Urine NGAL. (local urine collection participants only)	(SA 1) day 1 post urine collection
Change in Urine NGAL	Urine NGAL. (local urine collection participants only)	(SA 1) day 14 post urine collection
Change in Urine NGAL	Urine NGAL. (local urine collection participants only)	(SA 2) day 1 of intervention
Change in Urine NGAL	Urine NGAL. (local urine collection participants only)	(SA 2) 24-48 hours after intervention completion
Change in Cultivable Bacteria	urine culture. (local urine collection participants only)	(SA 1) day 1 post urine collection
Change in Cultivable Bacteria	urine culture. (local urine collection participants only)	(SA 1) day 14 post urine collection
Change in Cultivable Bacteria	urine culture. (local urine collection participants only)	(SA 2) day 1 of intervention
Change in Cultivable Bacteria	urine culture. (local urine collection participants only)	(SA 2) 24-48 hours after intervention completion
Change in Urine microbiome composition and function	Next generation sequencing for microbiome composition. (local urine collection participants only)	(SA 1) day 1 post urine collection
Change in Urine microbiome composition and function	Next generation sequencing for microbiome composition. (local urine collection participants only)	(SA 1) day 14 post urine collection
Change in Urine microbiome composition and function	Next generation sequencing for microbiome composition. (local urine collection participants only)	(SA 2) day 1 of intervention
Change in Urine microbiome composition and function	Next generation sequencing for microbiome composition. (local urine collection participants only)	(SA 2) 24-48 hours after intervention completion
NINDS Medical History CDE:	A brief medical history using body system categories	Baseline
Medical History Form	Medical history of participant	Baseline
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.	Baseline
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	Baseline

Collaborators and Investigators

• Sponsor: Medstar Health Research Institute
• Collaborators: Children's National Research Institute
• Investigators: Principal Investigator: Suzanne Groah, MD, MSPH, MedStar National Rehabilitation Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 10, 2020
• Primary Completion (ANTICIPATED): October 1, 2024
• Study Completion (ANTICIPATED): October 1, 2024

Study Registration Dates

• First Submitted: January 28, 2020
• First Submitted That Met QC Criteria: March 25, 2020
• First Posted (ACTUAL): March 26, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 15, 2022
• Last Update Submitted That Met QC Criteria: November 10, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Indwelling catheter; Foley catheter; Suprapubic Catheter
• Additional Relevant MeSH Terms: Nervous System Diseases; Urologic Diseases; Urinary Bladder Diseases; Neurologic Manifestations; Urinary Bladder, Neurogenic
• Other Study ID Numbers: STUDY00001782

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No