Clinical trial NCT04373512: Intravesical Lactobacillus to Reduce Urinary Symptoms After Spinal Cord Injury
Official title: Intravesical Lactobacillus to Reduce Urinary Symptoms After Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Spinal Cord Injuries
Neurogenic Bladder
Keywords: Intermittent Catheter
Lead sponsor: Medstar Health Research Institute
Sponsor class: OTHER
Collaborators: name: Children's National Research Institute
First posted: 2020-05-04
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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.

Eligibility 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.

Primary outcomes:
measure: Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter
timeFrame: (SA1) day of urine collection
measure: Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter
timeFrame: (SA1) day 1 post urine collection
measure: Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter
timeFrame: (SA1) day 2 post urine collection
measure: Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter
timeFrame: (SA1) day 3 post urine collection
measure: Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter
timeFrame: (SA2) Weekly up to 29 months
measure: Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter
timeFrame: (SA2) day 1 of intervention
measure: Urinary Symptom Questionnaire for Neurogenic Bladder- Intermittent catheter
timeFrame: (SA2) 24-48 hours after intervention completion
measure: Change in Urine white blood cell count
timeFrame: (SA1) day 1 post urine collection
measure: Change in Urine white blood cell count
timeFrame: (SA1) day 14 post urine collection
measure: Change in Urine white blood cell count
timeFrame: (SA 2) day 1 of intervention
measure: Change in Urine white blood cell count
timeFrame: (SA 2) 24-48 hours after intervention completion
measure: Change in Urine Nitrite
timeFrame: (SA1)day 1 post urine collection
measure: Change in Urine Nitrite
timeFrame: (SA1)day 14 post urine collection
measure: Change in Urine Nitrite
timeFrame: (SA 2) day 1 of intervention
measure: Change in Urine Nitrite
timeFrame: (SA 2) 24-48 hours after intervention completion
measure: Change in Urine NGAL
timeFrame: (SA1)day 1 post urine collection
measure: Change in Urine NGAL
timeFrame: (SA1)day 14 post urine collection
measure: Change in Urine NGAL
timeFrame: (SA 2) day 1 of intervention
measure: Change in Urine NGAL
timeFrame: (SA 2) 24-48 hours after intervention completion
measure: Change in Cultivable Bacteria
timeFrame: (SA1)day 1 post urine collection
measure: Change in Cultivable Bacteria
timeFrame: (SA1)day 14 post urine collection
measure: Change in Cultivable Bacteria
timeFrame: (SA 2) day 1 of intervention
measure: Change in Cultivable Bacteria
timeFrame: (SA 2) 24-48 hours after intervention completion
measure: Change in Urine microbiome composition
timeFrame: (SA1)day 1 post urine collection
measure: Change in Urine microbiome composition
timeFrame: (SA1)day 14 post urine collection
measure: Change in Urine microbiome composition
timeFrame: (SA 2) day 1 of intervention
measure: Change in Urine microbiome composition
timeFrame: (SA 2) 24-48 hours after intervention completion
measure: International SCI Lower Urinary Tract Function Basic Data Set
timeFrame: Day 1
measure: International SCI Core Data Set
timeFrame: Day 1
measure: NINDS Medical History CDE:
timeFrame: Day 1
measure: NINDS Prior and Concomitant Medications CDE
timeFrame: Day 1
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: MedStar National Rehabilitation Hospital
state: District of Columbia
Study officials:
affiliation: MedStar National Rehabilitation Hospital
name: Suzanne Groah, MD, MSPH
role: PRINCIPAL_INVESTIGATOR
References: