Intravesical LGG VS Saline Bladder Wash RCT

Intravesical Lactobacillus rhamnosusGG Versus Saline Bladder Wash: A Randomized, Controlled, Comparative Effectiveness Clinical Trial

This is the first ever comparative effectiveness study of an antibiotic-sparing novel self-management intervention to prevent complicated urinary tract infection (UTI).

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Injuries; Neurogenic Bladder
• Intervention / Treatment: Drug: Lactobacillus RhamnosusGG; Drug: Saline bladder wash

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 Compare the effects of Lactobacillus Rhamnosus GG (LGG®) + Saline bladder wash (BW) versus BW alone on USQNB-determined bladder (B1) and urine quality (B2) symptom burden (two co-primary outcomes) where participants self-manage in response to two trigger symptoms (cloudier and/or more foul-smelling urine).

SPECIFIC AIM 2 Compare the effects of LGG®+BW versus BW alone (in response to the two trigger symptoms) on key secondary outcomes: number of days lost from rehabilitation, work, and/or school; number of days symptomatic; number of interactions with the health care system due to urinary symptoms; exposure to antibiotics (days, volume).

SPECIFIC AIM 3 Compare the prophylactic effects of LGG®+BW versus BW alone on USQNB-determined bladder (B1) and urine quality (B2) symptom burden.

SPECIFIC AIM 4 Compare the prophylactic effects of LGG®+BW versus BW alone on key secondary outcomes: number of days lost from rehabilitation, work, and/or school; number of days symptomatic; number of interactions with the health care system due to urinary symptoms; exposure to antibiotics (days, volume).

SPECIFIC AIM 5 Compare satisfaction of participants who instilled LGG®+BW to satisfaction of those who instilled BW only and determine if dropouts are differentially attributable to either intervention being perceived by participants as "not working".

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Inger H Ljungberg, MPH; Phone Number: (202) 877-1694; Email: inger.h.ljungberg@medstar.net
• Study Contact Backup: Name: Emily Leonard, PhD; Phone Number: (202) 877-1844; Email: emily.m.leonard@medstar.net

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • MedStar National Rehabilitation Hospital
      • Contact: Inger H Ljungberg, MPH; Phone Number: (202) 877-1694; Email: inger.h.ljungberg@medstar.net
      • Contact: Allison M Maxwell, BA; Phone Number: 202-877-1560; Email: allison.m.maxwell@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
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18 years;
2. SCI at least 6 months duration;
3. NLUTD (as determined by their SCI physician or urologist);
4. Utilizing intermittent catheterization for bladder management; and
5. Community dwelling (discharged from the acute care setting).

Exclusion Criteria:

1. Known genitourinary pathology beyond neuropathic bladder (i.e., vesicoureteral reflux, bladder or kidney stones, etc.);
2. Use of prophylactic antibiotics;
3. Instillation of intravesical agents (e.g., gentamycin, saline; or Lactobacillus);
4. Immunodeficiency;
5. Any oral antibiotics within the past 2 weeks;
6. Psychologic or psychiatric conditions influencing the ability to follow instructions;
7. Participation in another study in which results would be confounded;
8. 6 months since prior exposure to intravesical LGG®; and
9. Active cancer (or within 5 years) or active autoimmune disorder

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intravesical Lactobacillus RhamnosusGG and Bladder Wash (Treatment Phase); LGG® (Culturelle Probiotic LGG®) will be used. This is the product we have used in the past and for which we have demonstrated safety, tolerability, and preliminary efficacy. For the LGG® instillation in response to trigger symptoms, 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 after the last catheterization prior to going to bed. Participants will be asked to return any remaining capsules at the end of the study. Participants will be instructed to complete the USQNB-IC at the time of symptoms (in real time) and daily during instillations for 2 days after the final instillation. Subjects will remain in this phase 6 months.	Drug: Lactobacillus RhamnosusGG; LGG® (Culturelle Probiotic LGG®) will be used. This is the product we have used in the past and for which we have demonstrated safety, tolerability, and preliminary efficacy. 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 after the last catheterization prior to going to bed. Participants will be asked to return any remaining capsules at the end of the study. Participants will be instructed to complete the USQNB-IC at the time of symptoms (in real time), and then continue completing the USQNB-IC at the determined frequency for the phase.; Other Names: Culturelle Probiotic LGG®
OTHER: Intravesical Bladder Wash (Treatment Phase); Participants will draw up the 45cc of normal saline into a 60cc syringe and instill via the intermittent catheter after the last catheterization prior to going to bed after trigger symptoms occur. Participants will be instructed to complete the USQNB-IC at the time of symptoms (in real time) and daily during instillations for 2 days after the final instillation. Subjects will remain in this phase 6 months.	Drug: Saline bladder wash; Participants will draw up the 45cc of normal saline into a 60cc syringe and instill via the intermittent catheter after the last catheterization prior to going to bed after trigger symptoms occur. Participants will be instructed to complete the USQNB-IC at the time of symptoms (in real time), and then continue completing the USQNB-IC at the determined frequency for the phase.
EXPERIMENTAL: Intravesical Lactobacillus RhamnosusGG and Bladder Wash (Prophylaxis Phase); LGG® (Culturelle Probiotic LGG®) will be used. This is the product we have used in the past and for which we have demonstrated safety, tolerability, and preliminary efficacy. For the LGG® instillation in response to trigger symptoms, 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 after the last catheterization prior to going to bed. They will then instill the LGG® mixture every 2 days for the remainder of the 6 months. Participants will be asked to return any remaining capsules at the end of the study. Participants will be instructed to complete the USQNB-IC at the time of symptoms (in real time) and biweekly post-instillation. Subjects will remain in this phase 6 months.	Drug: Lactobacillus RhamnosusGG; LGG® (Culturelle Probiotic LGG®) will be used. This is the product we have used in the past and for which we have demonstrated safety, tolerability, and preliminary efficacy. 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 after the last catheterization prior to going to bed. Participants will be asked to return any remaining capsules at the end of the study. Participants will be instructed to complete the USQNB-IC at the time of symptoms (in real time), and then continue completing the USQNB-IC at the determined frequency for the phase.; Other Names: Culturelle Probiotic LGG®
OTHER: Intravesical Bladder Wash (Prophylaxis Phase); Participants will draw up the 45cc of normal saline into a 60cc syringe and instill via the intermittent catheter after the last catheterization prior to going to bed after trigger symptoms occur. They will then instill the saline BW every 2 days for the remainder of the 6 months. Participants will be instructed to complete the USQNB-IC at the time of symptoms (in real time) and biweekly post-instillation. Subjects will remain in this phase 6 months.	Drug: Saline bladder wash; Participants will draw up the 45cc of normal saline into a 60cc syringe and instill via the intermittent catheter after the last catheterization prior to going to bed after trigger symptoms occur. Participants will be instructed to complete the USQNB-IC at the time of symptoms (in real time), and then continue completing the USQNB-IC at the determined frequency for the phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
International SCI Lower Urinary Tract Function Basic Data Set	A tool that describes urinary tract impairment, awareness of need to empty 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 outcome.	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 the medication, reason for medication, medication dose, frequency, start and end dates, and free text. Score is not associated with outcomes.	Day 1
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 and SA3) Weekly up to 18 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.	(SA1) Day 1 post-instillation (Phase 2: treatment phase)
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-instillation (Phase 2: treatment phase)
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.	(SA3) Twice weekly post-instillation for up to 6 months (Phase 3: prophylaxis phase)
Patient Satisfaction Survey	We developed a simple three-item patient satisfaction "survey" that will be requested from only those individuals who used the intervention (LGG® +BW or BW only) at the time of final USQNB-IC completion, or at the drop out visit (for those who did use the intervention at least once). Participants will be asked to estimate, using a scale from 0% <totally dissatisfied/would absolutely never do this>, through 50% <neither satisfied nor dissatisfied/might do this> to 100% <completely satisfied/would absolutely always do this>: How satisfied with the intervention you used are you?; Would you seek this intervention out and pay for it if insurance did not pay for it?; Would you use or recommend the intervention in response to symptoms, prophylactically, or both? :At the drop out visit, we will ask these three questions and one additional item for those who used the intervention at least once, "Are you dropping out because the intervention was not working for you?"	At final USQNB-IC completion (between 13 to 18 months) or at participant drop-out

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 13, 2022
• Primary Completion (ANTICIPATED): December 31, 2025
• Study Completion (ANTICIPATED): December 31, 2026

Study Registration Dates

• First Submitted: January 28, 2022
• First Submitted That Met QC Criteria: January 28, 2022
• First Posted (ACTUAL): February 9, 2022

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: Intermittent Catheter
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Urologic Diseases; Urinary Bladder Diseases; Neurologic Manifestations; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries; Urinary Bladder, Neurogenic
• Other Study ID Numbers: STUDY00004287

Drug and device information, study documents

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