Intravesical Lactobacillus to Reduce Urinary Symptoms After Spinal Cord Injury

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: Spinal Cord Injuries; Neurogenic Bladder
• Intervention / Treatment: Drug: Culturelle 10 Billion CFU Capsule (2 doses); Drug: Culturelle 10 Billion CFU Capsule (4 doses)

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 Type: Interventional
• Enrollment (Estimated): 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, MPH; 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
      • Contact: Amanda Rounds, PhD; Phone Number: 202-877-1591; Email: amanda.k.rounds@medstar.net
      • Contact: Inger Ljungberg, MPH; Phone Number: 202 877-1694; Email: inger.h.ljungberg@medstar.net
      • Principal Investigator: Suzanne Groah, MD,MSPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dosage Group; 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); 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; Other Names: Lactobacillus RhamnosusGG
Experimental: High Dosage Group; 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); 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; Other Names: Lactobacillus RhamnosusGG

What is the study measuring?

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

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): May 20, 2020
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: November 1, 2019
• First Submitted That Met QC Criteria: April 30, 2020
• First Posted (Actual): May 4, 2020

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 5, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Intermittent Catheter
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Urologic Diseases; Urinary Bladder Diseases; Neurologic Manifestations; Trauma, Nervous System; Spinal Cord Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Wounds and Injuries; Spinal Cord Injuries; Urinary Bladder, Neurogenic
• Other Study ID Numbers: STUDY00001124

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