Probiotics for Neurogenic Bladder

Overseen By Amanda K Rounds, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medstar Health Research Institute

Must not be taking: Antibiotics

Disqualifiers: Psychiatric conditions, Sexual activity, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1-2 days

182 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you've used oral or IV antibiotics in the past 2 weeks or are using prophylactic antibiotics.

What data supports the effectiveness of the treatment Culturelle 10 Billion CFU Capsule, Culturelle, Lactobacillus rhamnosus GG, LGG for neurogenic bladder?

Research shows that Lactobacillus rhamnosus GG (LGG) is safe and well-tolerated in people with neurogenic bladder, and it has been effective in reducing urinary symptoms in similar conditions. Additionally, LGG has shown potential in treating bladder cancer in mice, suggesting it may have beneficial effects on bladder health. ^{1 2 3 4 5}

Is Lactobacillus rhamnosus GG safe for use in humans?

Research shows that Lactobacillus rhamnosus GG, also known as Culturelle, is generally safe and well-tolerated in humans, including children and adults with neurogenic bladder. Studies have reported no significant adverse effects, and it is considered safe for consumption in various forms and doses. ^{3 5 6 7 8}

How is the treatment Culturelle 10 Billion CFU Capsule unique for neurogenic bladder?

Culturelle 10 Billion CFU Capsule, containing Lactobacillus rhamnosus GG, is unique for neurogenic bladder as it involves a novel approach of directly instilling probiotics into the bladder, which is different from traditional oral or systemic treatments. This method aims to manipulate the bladder's microbiome to improve symptoms, offering a non-antibiotic option that may help manage urinary symptoms without contributing to antibiotic resistance. ^{3 4 5 9 10}

Research Team

Suzanne Groah, MD,MSPH

Principal Investigator

MedStar National Rehabilitation Hospital

Eligibility Criteria

This trial is for people with neurogenic bladder for at least 6 months, using indwelling catheters. Premenopausal women not currently menstruating can join. Excluded are those on antibiotics, receiving antimicrobials to prevent UTI, unable to follow instructions due to mental health conditions, recently sexually active or in another conflicting study.

Inclusion Criteria

You are using a catheter to manage your bladder.

I am a premenopausal woman not having periods.

I have had bladder control issues due to nerve problems for at least 6 months.

Exclusion Criteria

You have had sex in the last 3 days.

I am taking antibiotics to prevent infections.

I have received bladder treatments to prevent urinary tract infections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravesical Lactobacillus Rhamnosus GG (LGG) instillation via indwelling catheter, with high and low dosage groups

1-2 days

1 visit (in-person)

Follow-up

Participants are monitored for changes in urinary symptoms, urine NGAL, white blood cell count, nitrites, cultivable bacteria, and urine microbiome composition

24-48 hours after intervention completion

Long-term Monitoring

Participants complete the USQNB-IDC weekly and return any remaining kits if urinary symptoms do not occur during the 29-month study period

Up to 29 months

Treatment Details

Interventions

• Culturelle 10 Billion CFU Capsule

Trial Overview The trial tests intravesical Lactobacillus RhamnosusGG (LGG®) delivered directly into the bladder via a catheter. The goal is to find the best dose that reduces urinary symptoms and improves urine health without causing harm before moving on to a larger scale study.

Participant Groups

Group I: High dosage Active Control 1 Intervention

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 indwelling catheter (the catheter will not be changed as this would represent 2 interventions). Participants will be instructed the plug their catheter for 1 hour. 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.

Group II: Low Dosage Active Control 1 Intervention

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 indwelling catheter (the catheter will not be changed as this would represent 2 interventions). Participants will be instructed the plug their catheter for 1 hour. 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.

Culturelle 10 Billion CFU Capsule is already approved in United States, European Union for the following indications:

Approved in United States as Culturelle for:

• Digestive health support
• Immune system support

Approved in European Union as Lactobacillus rhamnosus GG for:

• Gastrointestinal health
• Immune system support

Who Is Running the Clinical Trial?

Medstar Health Research Institute

Lead Sponsor

Trials

202

Recruited

187,000+

Children's National Research Institute

Collaborator

Trials

227

Recruited

258,000+

Findings from Research

In a study involving 96 adults and 7 children with spinal cord injury and neurogenic lower urinary tract dysfunction, self-administered intravesical Lactobacillus rhamnosus GG (LGG) significantly reduced the burden of clinically actionable urinary symptoms and improved urine quality after treatment.

Participants who used LGG reported significant improvements in their urinary symptoms, particularly in 'clinically actionable' and 'urine quality' categories, suggesting that LGG could be a beneficial intervention for managing urinary symptoms in individuals using intermittent catheterization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Intravesical Lactobacillus Rhamnosus GG on Urinary Symptom Burden in People with Neurogenic Lower Urinary Tract Dysfunction. Tractenberg, RE., Groah, SL., Frost, JK., et al.[2022]

In a study using a murine model of bladder cancer, Lactobacillus rhamnosus GG (LGG) demonstrated a higher cure rate (89%) compared to the standard BCG immunotherapy (77%), suggesting it could be a more effective treatment option.

LGG therapy not only increased the number of cured mice but also enhanced immune responses by recruiting neutrophils and macrophages to the tumor site, indicating a strong mechanism of action in combating bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus rhamnosus GG induces tumor regression in mice bearing orthotopic bladder tumors. Seow, SW., Cai, S., Rahmat, JN., et al.[2022]

A Phase Ia safety study involving 10 patients (5 children and 5 adults) found that a single instillation of Lactobacillus rhamnosus GG was well-tolerated, with minimal side effects reported, indicating its potential safety for patients with neuropathic bladder.

The study showed that Lactobacillus was present in the urinary microbiomes of most participants both before and after the instillation, suggesting that the probiotic can be successfully introduced into the bladder microbiome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single intravesical instillation of Lactobacillus rhamnosus GG is safe in children and adults with neuropathic bladder: A phase Ia clinical trial. Forster, CS., Hsieh, MH., Pérez-Losada, M., et al.[2022]

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]

In a study of 103 individuals with neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury or disease, self-instilled Lactobacillus rhamnosus GG (LGG®) was found to be safe and well tolerated for managing inflammatory urinary symptoms.

Out of 74 adults and 6 children who completed the study, there were no significant adverse events linked to the use of LGG®, indicating that it can be a viable self-management option for urinary symptoms in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical Lactobacillus rhamnosus GG is safe and well tolerated in adults and children with neurogenic lower urinary tract dysfunction: first-in-human trial. Groah, SL., Rounds, AK., Ljungberg, IH., et al.[2023]

In a study involving 131 participants, taking Lactobacillus reuteri NCIMB 30242 capsules twice daily for 9 weeks showed no significant adverse effects compared to a placebo, indicating its safety for consumption.

Clinical assessments of blood chemistry and hematology revealed no clinically significant differences between the probiotic and placebo groups, confirming that L. reuteri is well tolerated in the evaluated population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of clinical safety and tolerance of a Lactobacillus reuteri NCIMB 30242 supplement capsule: a randomized control trial. Jones, ML., Martoni, CJ., Di Pietro, E., et al.[2022]

Lactobacillus rhamnosus GG (LGG) is a highly resilient probiotic that can survive harsh stomach conditions and has been shown to protect the gut by enhancing intestinal health and reducing inflammation, making it effective for various gastrointestinal issues and infections.

Research supports LGG's role in promoting immune responses and inhibiting harmful pathogens, with evidence from numerous randomized controlled trials and meta-analyses indicating its potential benefits for conditions like diarrhea, irritable bowel syndrome, and even respiratory infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thirty Years of Lactobacillus rhamnosus GG: A Review. Capurso, L.[2022]

In a study involving 34 healthy volunteers, the probiotic strain Lactobacillus rhamnosus PRSF-L477 was found to be well tolerated, with no significant gastrointestinal symptoms or changes in defecation patterns reported during a 3-week administration period.

The strain was safely administered at a daily dose of 1 × 10¹¹ colony-forming units (cfu), with no adverse effects on blood parameters or serious health issues observed, confirming its safety for use in healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerance and safety of the potentially probiotic strain Lactobacillus rhamnosus PRSF-L477: a randomised, double-blind placebo-controlled trial in healthy volunteers. Wind, RD., Tolboom, H., Klare, I., et al.[2022]

In a pilot study involving two patients with spinal cord injury, the administration of probiotics (Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri) alongside antibiotics significantly reduced urinary TNF-alpha levels, indicating a potential anti-inflammatory effect.

The patient receiving probiotics and using intermittent catheterization showed better inflammatory responses compared to the placebo group with an indwelling catheter, suggesting that probiotics may help manage UTIs in individuals with spinal cord injuries, but further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 may help downregulate TNF-Alpha, IL-6, IL-8, IL-10 and IL-12 (p70) in the neurogenic bladder of spinal cord injured patient with urinary tract infections: a two-case study. Anukam, KC., Hayes, K., Summers, K., et al.[2021]

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]

References

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

Effects of Intravesical Lactobacillus Rhamnosus GG on Urinary Symptom Burden in People with Neurogenic Lower Urinary Tract Dysfunction. [2022]

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

Lactobacillus rhamnosus GG induces tumor regression in mice bearing orthotopic bladder tumors. [2022]

3. England pubmed.ncbi.nlm.nih.gov

A single intravesical instillation of Lactobacillus rhamnosus GG is safe in children and adults with neuropathic bladder: A phase Ia clinical trial. [2022]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Intravesical Lactobacillus rhamnosus GG is safe and well tolerated in adults and children with neurogenic lower urinary tract dysfunction: first-in-human trial. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Evaluation of clinical safety and tolerance of a Lactobacillus reuteri NCIMB 30242 supplement capsule: a randomized control trial. [2022]

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

Thirty Years of Lactobacillus rhamnosus GG: A Review. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Tolerance and safety of the potentially probiotic strain Lactobacillus rhamnosus PRSF-L477: a randomised, double-blind placebo-controlled trial in healthy volunteers. [2022]

9. Egypt pubmed.ncbi.nlm.nih.gov

Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 may help downregulate TNF-Alpha, IL-6, IL-8, IL-10 and IL-12 (p70) in the neurogenic bladder of spinal cord injured patient with urinary tract infections: a two-case study. [2021]

10. 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]