Probiotic vs Saline Wash for Preventing UTIs in Neurogenic Bladders

Overseen By Suzanne Groah, MD, MSPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medstar Health Research Institute

Must not be taking: Prophylactic antibiotics, Oral antibiotics

Disqualifiers: Genitourinary pathology, Immunodeficiency, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

120 Participants Needed

Trial Summary

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are using prophylactic antibiotics or have taken oral antibiotics in the past 2 weeks.

What data supports the effectiveness of the treatment Lactobacillus rhamnosus GG for preventing UTIs in neurogenic bladders?

Research suggests that probiotics, including Lactobacillus rhamnosus strains, can help prevent urinary tract infections (UTIs) by acting as a barrier to harmful bacteria and producing substances that inhibit their growth. These probiotics have shown promise in reducing recurrent UTIs in women and may offer a non-antibiotic prevention strategy. ^{1 2 3 4 5}

Is the use of Lactobacillus rhamnosus GG generally safe for humans?

Lactobacillus rhamnosus GG is generally considered safe for most people, but there have been rare cases of bloodstream infections (bacteremia) in individuals with weakened immune systems or specific health conditions. It is important to consult with a healthcare provider before using probiotics, especially for those with compromised health. ^{3 6 7 8 9}

How is the treatment Lactobacillus rhamnosus GG different from other treatments for preventing UTIs in neurogenic bladders?

Lactobacillus rhamnosus GG is a probiotic treatment that works by promoting the growth of beneficial bacteria to prevent harmful bacteria from causing urinary tract infections, offering a non-antibiotic alternative that may help reduce antibiotic resistance. ^{1 2 3 10 11}

Research Team

Suzanne Groah, MD,MSPH

Principal Investigator

MedStar National Rehabilitation Hospital

Eligibility Criteria

This trial is for adults over 18 with spinal cord injury (SCI) for at least 6 months, who manage their bladder using intermittent catheterization and live outside of acute care settings. It's not open to those with other genitourinary issues, current antibiotic use, recent intravesical treatments or oral antibiotics, immune deficiencies, certain psychological conditions, participation in conflicting studies, recent LGG® exposure or active cancer/autoimmune diseases.

Inclusion Criteria

I use a catheter sometimes to help empty my bladder.

You have had a spinal cord injury for at least 6 months.

I live at home and not in a hospital.

Exclusion Criteria

I have received bladder treatments like gentamycin or saline.

I am taking antibiotics to prevent infections.

I have a bladder or kidney condition, not including neuropathic bladder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Lactobacillus Rhamnosus GG (LGG) + Saline bladder wash or Saline bladder wash alone in response to trigger symptoms for 6 months.

6 months

Daily self-administration with real-time symptom tracking

Prophylaxis

Participants continue with either LGG + Saline bladder wash or Saline bladder wash alone every 2 days for 6 months.

6 months

Biweekly post-instillation monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 weeks

Treatment Details

Interventions

• Lactobacillus RhamnosusGG
• Saline bladder wash

Trial Overview The study tests a new way to prevent urinary tract infections without antibiotics in people with neurogenic bladders due to SCI. Participants will either receive an innovative treatment called Lactobacillus Rhamnosus GG directly into the bladder or a standard saline wash as a comparison.

Participant Groups

Group I: Intravesical Lactobacillus RhamnosusGG and Bladder Wash (Treatment Phase) Experimental Treatment 1 Intervention

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.

Group II: Intravesical Lactobacillus RhamnosusGG and Bladder Wash (Prophylaxis Phase) Experimental Treatment 1 Intervention

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.

Group III: Intravesical Bladder Wash (Treatment Phase) Experimental Treatment 1 Intervention

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.

Group IV: Intravesical Bladder Wash (Prophylaxis Phase) Experimental Treatment 1 Intervention

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.

Lactobacillus RhamnosusGG is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Lactobacillus rhamnosus GG for:

• Prevention of antibiotic-associated diarrhea
• Prevention of urinary tract infections
• Support for immune system

Approved in United States as Lactobacillus rhamnosus GG for:

• Prevention of antibiotic-associated diarrhea
• Prevention of urinary tract infections
• Support for immune system

Approved in Canada as Lactobacillus rhamnosus GG for:

• Prevention of antibiotic-associated diarrhea
• Prevention of urinary tract infections
• Support for immune system

Who Is Running the Clinical Trial?

Medstar Health Research Institute

Lead Sponsor

Trials

202

Recruited

187,000+

Findings from Research

Probiotics, particularly Lactobacillus strains, show promise as a safe alternative to antibiotics for treating urinary tract infections (UTIs), especially those caused by Proteus mirabilis, which is often resistant to conventional treatments.

The study aims to identify the most effective Lactobacillus strains that can inhibit P. mirabilis growth on bladder and prostatic tissues, potentially enhancing UTI management without the side effects associated with antibiotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Different Activity of Lactobacillus spp. against Two Proteus mirabilis Isolated Clinical Strains in Different Anatomical Sites In Vitro: An Explorative Study to Improve the Therapeutic Approach. Fusco, A., Savio, V., Chiaromonte, A., et al.[2023]

This study investigates the effectiveness of probiotic therapy using Lactobacillus and Bifidobacterium strains in preventing urinary tract infections (UTIs) in individuals with spinal cord injury (SCI), a population prone to antibiotic-resistant infections.

Conducted as a multi-site, randomized, double-blind, placebo-controlled trial with participants receiving 24 weeks of treatment, the primary outcome is the time to symptomatic UTI, which could provide a non-antibiotic strategy to reduce UTI incidence and combat antibiotic resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotics [LGG-BB12 or RC14-GR1] versus placebo as prophylaxis for urinary tract infection in persons with spinal cord injury [ProSCIUTTU]: a study protocol for a randomised controlled trial. Lee, BB., Toh, SL., Ryan, S., et al.[2022]

Probiotics, specifically Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum B-54 and RC-14, have shown potential in preventing urinary tract infections (UTIs) by colonizing the vagina and blocking harmful bacteria from reaching the bladder.

While probiotic therapy is considered safe, there are currently no reliable products available specifically for UTI prevention, highlighting the need for further development and clinical verification of effective probiotic strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic Therapy and Functional Foods for Prevention of Urinary Tract Infections: State of the Art and Science. Reid, G.[2020]

Probiotic lactobacilli strains, particularly Lactobacillus rhamnosus GR1 and Lactobacillus reuteri RC14, show promise in preventing recurrent urinary tract infections (UTIs) in females, with a pooled risk ratio of 0.684 indicating a significant reduction in UTI episodes based on a review of 9 clinical trials involving 726 patients.

While the results support the use of probiotics as a non-antibiotic approach to UTI prevention, the studies showed significant variability and limited follow-up duration, highlighting the need for more rigorous randomized controlled trials to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Lactobacillus spp. to prevent recurrent urinary tract infections in females. Ng, QX., Peters, C., Venkatanarayanan, N., et al.[2018]

The study identified three strains of lactic acid bacteria (LAB) that showed significant antimicrobial activity against uropathogens responsible for urinary tract infections in children, suggesting their potential as probiotic candidates.

Using the agar disk diffusion assay, the antimicrobial effectiveness of these LAB strains increased notably by the fourth day of culture, indicating that these probiotics could be developed for treating and preventing urinary tract infections in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of lactic acid bacteria isolates on the urinary tract pathogens to infants in vitro. Lim, IS., Lee, HS., Kim, WY.[2021]

Probiotic agents, like Lactobacillus rhamnosus GG, are generally safe but can lead to complications such as bacteremia, especially in vulnerable populations like children with short gut syndrome.

In this case, the identity of the bacteria found in the child's bloodstream matched the strain from the probiotic tablet, highlighting the potential risks associated with probiotic use in certain medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus rhamnosus GG bacteremia associated with probiotic use in a child with short gut syndrome. De Groote, MA., Frank, DN., Dowell, E., et al.[2019]

Lactobacillus rhamnosus GG has been shown to effectively manage acute diarrhea and antibiotic-associated diarrhea in children, potentially shortening the duration and severity of symptoms.

This probiotic strain may also help in managing infant colic and promoting earlier tolerance to cow's milk protein allergy, as well as reducing the risk of developing atopic dermatitis when administered during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approach to probiotics in pediatrics: the role of Lactobacillus rhamnosus GG. Boggio Marzet, C., Burgos, F., Del Compare, M., et al.[2022]

A randomized, double-blind, placebo-controlled trial involving 619 children aged 2-6 years found that while Lacticaseibacillus rhamnosus GG DSM 33156 was well tolerated, it did not significantly reduce the incidence of acute upper respiratory tract infections (URTIs) compared to placebo.

However, the study indicated that children who consumed L. rhamnosus GG DSM 33156 experienced alleviated symptoms during URTIs, suggesting potential benefits in symptom management despite no significant impact on infection rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacticaseibacillus rhamnosus GG DSM 33156 effects on pathogen defence in the upper respiratory tract: a randomised, double-blind, placebo-controlled paediatric trial. Damholt, A., Keller, MK., Baranowski, K., et al.[2022]

Two cases of bacteraemia caused by Lacticaseibacillus rhamnosus were reported in patients in intensive care units, highlighting that while these bacteria are generally safe, they can cause serious infections in vulnerable individuals.

The study emphasizes the need for careful evaluation of probiotic safety, especially in immunocompromised patients, and suggests that guidelines should be developed to manage the use of probiotics in high-risk groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacteraemia Caused by Probiotic Strains of Lacticaseibacillus rhamnosus-Case Studies Highlighting the Need for Careful Thought before Using Microbes for Health Benefits. Mikucka, A., Deptuła, A., Bogiel, T., et al.[2022]

Lactobacillus crispatus, L. jensenii, and L. gasseri were effective in inhibiting the growth of E. coli, the main cause of urinary tract infections, while L. iners showed no inhibitory effect.

The inhibition of E. coli growth was linked to the acidity of the Lactobacillus-conditioned media, suggesting that these probiotics could be used as a natural strategy to help prevent UTIs by maintaining a low pH environment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Vaginal Lactobacillus Species on Escherichia coli Growth. Hudson, PL., Hung, KJ., Bergerat, A., et al.[2021]

In a double-blinded randomized controlled trial involving 7 healthy pre-menopausal women, the oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 did not significantly change the ratio of uropathogens to Lactobacillus in urine samples over 3 months.

No adverse events were reported, but the probiotics were not detected in the urine, indicating that this specific probiotic intervention may not be effective in preventing urinary tract infections in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral probiotics and the female urinary microbiome: a double-blinded randomized placebo-controlled trial. Wolff, BJ., Price, TK., Joyce, CJ., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of Different Activity of Lactobacillus spp. against Two Proteus mirabilis Isolated Clinical Strains in Different Anatomical Sites In Vitro: An Explorative Study to Improve the Therapeutic Approach. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Probiotics [LGG-BB12 or RC14-GR1] versus placebo as prophylaxis for urinary tract infection in persons with spinal cord injury [ProSCIUTTU]: a study protocol for a randomised controlled trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Probiotic Therapy and Functional Foods for Prevention of Urinary Tract Infections: State of the Art and Science. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Use of Lactobacillus spp. to prevent recurrent urinary tract infections in females. [2018]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

The effect of lactic acid bacteria isolates on the urinary tract pathogens to infants in vitro. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Lactobacillus rhamnosus GG bacteremia associated with probiotic use in a child with short gut syndrome. [2019]

7. Argentina pubmed.ncbi.nlm.nih.gov

Approach to probiotics in pediatrics: the role of Lactobacillus rhamnosus GG. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Lacticaseibacillus rhamnosus GG DSM 33156 effects on pathogen defence in the upper respiratory tract: a randomised, double-blind, placebo-controlled paediatric trial. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Bacteraemia Caused by Probiotic Strains of Lacticaseibacillus rhamnosus-Case Studies Highlighting the Need for Careful Thought before Using Microbes for Health Benefits. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Effect of Vaginal Lactobacillus Species on Escherichia coli Growth. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Oral probiotics and the female urinary microbiome: a double-blinded randomized placebo-controlled trial. [2022]