Intravesical LGG VS Saline Bladder Wash RCT

MedStar Health

Status and phase: Enrolling; Phase 2

Conditions: Spinal Cord Injuries; Neurogenic Bladder

Treatments: Drug: Saline bladder wash; Drug: Lactobacillus RhamnosusGG

Study type: Interventional

Funder types: Other

Identifiers

NCT05230511

STUDY00004287

Details and patient eligibility

About

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

Full 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".

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

120 participants in 4 patient groups

Intravesical Lactobacillus RhamnosusGG and Bladder Wash (Treatment Phase)

Experimental group

Description:

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.

Treatment:

Drug: Lactobacillus RhamnosusGG

Intravesical Bladder Wash (Treatment Phase)

Other group

Description:

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.

Treatment:

Drug: Saline bladder wash

Intravesical Lactobacillus RhamnosusGG and Bladder Wash (Prophylaxis Phase)

Experimental group

Description:

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.

Treatment:

Drug: Lactobacillus RhamnosusGG

Intravesical Bladder Wash (Prophylaxis Phase)

Other group

Description:

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.

Treatment:

Drug: Saline bladder wash