Intravesical Lactobacillus to Reduce Urinary Symptoms After Spinal Cord Injury

• ClinicalTrials.gov Identifier: NCT04373512
• Recruitment Status: Recruiting
• First Posted: May 4, 2020
• Last Update Posted: November 15, 2022
• Sponsor: Medstar Health Research Institute
• Collaborator: Children's National Research Institute
• Information provided by (Responsible Party): Medstar Health Research Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Spinal Cord Injuries; Neurogenic Bladder	Drug: Culturelle 10 Billion CFU Capsule (2 doses); Drug: Culturelle 10 Billion CFU Capsule (4 doses)	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 182 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention 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)
• Primary Purpose: Prevention
• Official Title: Intravesical Lactobacillus to Reduce Urinary Symptoms After Spinal Cord Injury
• Actual Study Start Date: May 20, 2020
• Estimated Primary Completion Date: August 2023
• Estimated Study Completion Date: August 2023

Arms and Interventions

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 Name: 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 Name: Lactobacillus RhamnosusGG

Outcome Measures

Primary Outcome Measures :

1. Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter [ Time Frame: (SA1) day of urine collection ]
   Will measure change in urinary symptoms for those that use an intermittent catheter. Higher scores may mean worse outcomes.
2. Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter [ Time Frame: (SA1) day 1 post urine collection ]
   Will measure change in urinary symptoms for those that use an intermittent catheter. Higher scores may mean worse outcomes.
3. Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter [ Time Frame: (SA1) day 2 post urine collection ]
   Will measure change in urinary symptoms for those that use an intermittent catheter. Higher scores may mean worse outcomes.
4. Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter [ Time Frame: (SA1) day 3 post urine collection ]
   Will measure change in urinary symptoms for those that use an intermittent catheter. Higher scores may mean worse outcomes.
5. Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter [ Time Frame: (SA2) Weekly up to 29 months ]
   Will measure change in urinary symptoms for those that use an intermittent catheter. Higher scores may mean worse outcomes.
6. Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter [ Time Frame: (SA2) day 1 of intervention ]
   Will measure change in urinary symptoms for those that use an intermittent catheter. Higher scores may mean worse outcomes.
7. Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter [ Time Frame: (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.
8. Change in Urine white blood cell count [ Time Frame: (SA1) day 1 post urine collection ]
   urinalysis
9. Change in Urine white blood cell count [ Time Frame: (SA1) day 14 post urine collection ]
   urinalysis
10. Change in Urine white blood cell count [ Time Frame: (SA 2) day 1 of intervention ]
    urinalysis
11. Change in Urine white blood cell count [ Time Frame: (SA 2) 24-48 hours after intervention completion ]
    urinalysis
12. Change in Urine Nitrite [ Time Frame: (SA1)day 1 post urine collection ]
    urinalysis
13. Change in Urine Nitrite [ Time Frame: (SA1)day 14 post urine collection ]
    urinalysis
14. Change in Urine Nitrite [ Time Frame: (SA 2) day 1 of intervention ]
    urinalysis
15. Change in Urine Nitrite [ Time Frame: (SA 2) 24-48 hours after intervention completion ]
    urinalysis
16. Change in Urine NGAL [ Time Frame: (SA1)day 1 post urine collection ]
    Urine NGAL
17. Change in Urine NGAL [ Time Frame: (SA1)day 14 post urine collection ]
    Urine NGAL
18. Change in Urine NGAL [ Time Frame: (SA 2) day 1 of intervention ]
    Urine NGAL
19. Change in Urine NGAL [ Time Frame: (SA 2) 24-48 hours after intervention completion ]
    Urine NGAL
20. Change in Cultivable Bacteria [ Time Frame: (SA1)day 1 post urine collection ]
    urine culture
21. Change in Cultivable Bacteria [ Time Frame: (SA1)day 14 post urine collection ]
    urine culture
22. Change in Cultivable Bacteria [ Time Frame: (SA 2) day 1 of intervention ]
    urine culture
23. Change in Cultivable Bacteria [ Time Frame: (SA 2) 24-48 hours after intervention completion ]
    urine culture
24. Change in Urine microbiome composition [ Time Frame: (SA1)day 1 post urine collection ]
    proportion of different bacterial species
25. Change in Urine microbiome composition [ Time Frame: (SA1)day 14 post urine collection ]
    proportion of different bacterial species
26. Change in Urine microbiome composition [ Time Frame: (SA 2) day 1 of intervention ]
    proportion of different bacterial species
27. Change in Urine microbiome composition [ Time Frame: (SA 2) 24-48 hours after intervention completion ]
    proportion of different bacterial species
28. International SCI Lower Urinary Tract Function Basic Data Set [ Time Frame: 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
29. International SCI Core Data Set [ Time Frame: Day 1 ]
    Includes date of injury, dates of initial hospitalization admission and discharge, neurological data. Score is not associated with outcomes
30. NINDS Medical History CDE: [ Time Frame: Day 1 ]
    A brief medical history using body system categories. Score is not associated with outcomes
31. NINDS Prior and Concomitant Medications CDE [ Time Frame: 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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Amanda K Rounds, PhD; (202) 877-1591; Amanda.K.Rounds@medstar.net

Contact: Inger H Ljungberg, MPH; (202) 877-1694; inger.h.ljungberg@medstar.net

Locations

United States, District of Columbia

MedStar National Rehabilitation Hospital; Recruiting

Washington, District of Columbia, United States, 20010

Contact: Amanda Rounds, PhD 202-877-1591 amanda.k.rounds@medstar.net

Contact: Inger Ljungberg, MPH 202 877-1694 inger.h.ljungberg@medstar.net

Principal Investigator: Suzanne Groah, MD,MSPH

Sponsors and Collaborators

Medstar Health Research Institute

Children's National Research Institute

Investigators

• Principal Investigator: Suzanne Groah, MD, MSPH; MedStar National Rehabilitation Hospital

More Information

• Responsible Party: Medstar Health Research Institute
• ClinicalTrials.gov Identifier: NCT04373512
• Other Study ID Numbers: STUDY00001124
• First Posted: May 4, 2020
• Last Update Posted: November 15, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Medstar Health Research Institute:

Intermittent Catheter

Additional relevant MeSH terms:

Spinal Cord Injuries; Urinary Bladder, Neurogenic; Wounds and Injuries; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Neurologic Manifestations; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases