Probiotics for Neurogenic Bladder
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Medstar Health Research Institute
No Placebo Group
Prior Safety Data
Approved in 2 jurisdictions
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.
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.
12689Is 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.
45789What 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.
368910Will 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.
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
I am a premenopausal woman not having periods.
I have had bladder control issues due to nerve problems for at least 6 months.
I have a physical disability and live in the community.
Exclusion Criteria
I am taking antibiotics to prevent infections.
I have received bladder treatments to prevent urinary tract infections.
I have not taken any antibiotics in the last 2 weeks.
Participant Groups
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.
2Treatment groups
Active Control
Group I: High dosageActive Control1 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 DosageActive Control1 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
MedStar National Rehabilitation HospitalWashington, United States
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Who is running the clinical trial?
Medstar Health Research InstituteLead Sponsor
Children's National Research InstituteCollaborator
References
Probiotic Therapy and Functional Foods for Prevention of Urinary Tract Infections: State of the Art and Science. [2020]In the past year, interest has heightened in the potential for probiotics to prevent urinary tract infection (UTI). Mainly, this has been due to concerns about antibiotic resistance and recognition of the scientific efficacy of probiotics. The critical factors in any successful application of probiotics to patient care are the scientific basis for selecting probiotic strains and clinical verification that they are effective against the recurrence of UTI. Three strains--Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum B-54 and RC-14--have been shown to colonize the vagina and act as a barrier to the ascension of uropathogens into the bladder. Their ability to produce growth and adhesion antagonists against urogenital pathogens is clinically important, because these appear to be important mechanisms of action. Probiotic therapy has been shown to be safe, but too few reliable products are on the market, and none are yet available for use against UTI. Given the right strains and delivery system, probiotic therapy could provide the first new UTI-prevention system in 40 years, and may help in the management of recurrent UTI.
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]The management of urinary tract infection (UTI) in individuals with spinal cord injury (SCI) continues to be of concern, due to complications that can occur. An emerging concept that is a common underlying pathophysiological process is involved, wherein pathogens causing UTI have a role in inflammatory progression. We hypothesized that members of the commensal flora, such as lactobacilli, may counter this reaction through anti-inflammatory mediation. This was assessed in a pilot two-patient study in which probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri were administered to one patient and placebo to another, both along with antibiotics to treat acute UTI. Urinary TNF-alpha was significantly downregulated (P = .015) in the patient who received the probiotic and who used intermittent catheterization compared with patient on placebo and using an indwelling catheter. The extent to which this alteration resulted in improved well-being in spinal cord injured patients remains to be determined in a larger study.
Lactobacillus rhamnosus GG induces tumor regression in mice bearing orthotopic bladder tumors. [2022]The present gold standard for bladder cancer is Mycobacterium bovis, Bacillus Calmette Guerin (BCG) immunotherapy. But it has a non-responder rate of 30-50% and side effects are common. Lactobacillus casei strain Shirota has been reported to reduce the incidence of recurrence in bladder cancer patients and to cure tumor-bearing mice. Our aim was to determine if Lactobacillus rhamnosus GG (LGG) could be as efficacious as BCG in a murine model of bladder cancer. MB49 bladder cancer cells secreting human prostate-specific antigen were implanted orthotopically in female C57BL/6 mice and urinary prostate-specific antigen levels were used as a marker of tumor growth. Mice were treated with either live or lyophilized LGG given via intravesical instillation, or both oral and intravesical LGG given once a week for a period of 6 weeks starting at day 4 after tumor implantation. A comparison of LGG and BCG immunotherapy was also carried out. LGG therapy (live or lyophilized) significantly (P = 0.006) increased the number of cured mice. Cytokine arrays and immune cell recruitment analysis revealed differences between untreated, treated, cured, and tumor-bearing mice. LGG therapy restored XCL1 levels to those in healthy bladders. LGG also recruited large numbers of neutrophils and macrophages to the tumor site. Intravesical LGG and BCG immunotherapy had cure rates of 89 and 77%, respectively, compared with 20% in untreated mice. LGG has the potential to replace BCG immunotherapy for the treatment of bladder cancer.
Tolerance and safety of the potentially probiotic strain Lactobacillus rhamnosus PRSF-L477: a randomised, double-blind placebo-controlled trial in healthy volunteers. [2022]In Europe, the species Lactobacillus rhamnosus is currently on the Qualified Presumption of Safety list used by the European Food Safety Authority (EFSA) for internal safety assessment, but according to the EFSA the species should remain a topic of surveillance. In the present study, the safety and tolerance of the potentially probiotic strain L. rhamnosus PRSF-L477 was investigated in a placebo-controlled double-blind volunteer trial following FAO/WHO guidelines. A total of thirty-four subjects received daily doses of 1 × 10¹¹ colony-forming units (cfu) of L. rhamnosus PRSF-L477 (n 17) or placebo (n 17) for a period of 3 weeks, followed by a wash-out period of another 3 weeks. A questionnaire on gastrointestinal tolerance and a diary was kept daily to record compliance throughout these 6 weeks. Faecal and blood samples were collected for microbiological and haematological analysis. The recorded gastrointestinal symptoms, defecation frequency and stool consistency were not influenced indicating that L. rhamnosus PRSF-L477 was well tolerated. The species L. rhamnosus was detected in the faeces of sixteen out of seventeen subjects of the probiotic group during the intervention period. Using pulsed-field gel electrophoresis, re-isolates of L. rhamnosus PRSF-L477 were confirmed in nine of these subjects. Antibiotic susceptibility profiles of these re-isolates were unchanged compared with PRSF-L477. No clinically relevant changes in blood parameters such as liver and kidney function and no serious adverse events appeared during and after administration. Therefore, we conclude that L. rhamnosus PRSF-L477 can safely be administrated to healthy subjects at a daily dose of 1 × 10¹¹ cfu.
Evaluation of clinical safety and tolerance of a Lactobacillus reuteri NCIMB 30242 supplement capsule: a randomized control trial. [2022]A significant number of human clinical trials have reported no adverse effects associated with consumption of Lactobacillus reuteri (L. reuteri). In the present study, the clinical safety and toxicology of oral ingestion of supplement capsules containing L. reuteri NCIMB 30242 was investigated. A randomized group of 131 subjects received a dose of 2.9×10⁹ CFU L. reuteri NCIMB 30242 capsules (n=67) or placebo capsules (n=64) twice daily for 9 weeks. Clinical chemistry and hematological parameters of safety were analyzed. The frequency, duration and intensity of adverse events (AE)s and clinical significance of safety parameters were recorded for both groups. No clinically significant differences between the probiotic capsule and placebo capsule treated groups were detected in either the blood clinical chemistry or hematology results. The frequency and intensity of AEs was similar in the two groups. These results demonstrate that administration of a twice daily dose of 2.9×10⁹ CFU was safe and well tolerated in the population evaluated over 9 weeks.
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]Urinary tract infections [UTIs] are very common in people with Spinal Cord Injury [SCI]. UTIs are increasingly difficult and expensive to treat as the organisms that cause them become more antibiotic resistant. Among the SCI population, there is a high rate of multi-resistant organism [MRO] colonisation. Non-antibiotic prevention strategies are needed to prevent UTI without increasing resistance. Probiotics have been reported to be beneficial in preventing UTIs in post-menopausal women in several in vivo and in vitro studies. The main aim of this study is to determine whether probiotic therapy with combinations of Lactobacillus reuteri RC-14 + Lactobacillus rhamnosus GR-1 [RC14-GR1] and/or Lactobacillus rhamnosus GG + Bifidobacterium BB-12 [LGG-BB12] are effective in preventing UTI in people with SCI compared to placebo.
Thirty Years of Lactobacillus rhamnosus GG: A Review. [2022]Lactobacillus rhamnosus GG (LGG) was the first strain belonging to the genus Lactobacillus to be patented in 1989 thanks to its ability to survive and to proliferate at gastric acid pH and in medium containing bile, and to adhere to enterocytes. Furthermore LGG is able to produces both a biofilm that can mechanically protect the mucosa, and different soluble factors beneficial to the gut by enhancing intestinal crypt survival, diminishing apoptosis of the intestinal epithelium, and preserving cytoskeletal integrity. Moreover LGG thanks to its lectin-like protein 1 and 2 inhibits some pathogens such as Salmonella species. Finally LGG is able to promote type 1 immune-responsiveness by reducing the expression of several activation and inflammation markers on monocytes and by increasing the production of interleukin-10, interleukin-12 and tumor necrosis factor-α in macrophages. A large number of research data on Lactobacillus GG is the basis for the use of this probiotic for human health. In this review we have considered predominantly randomized controlled trials, meta-analysis, Cochrane Review, guide lines of Scientific Societies and anyway studies whose results were evaluated by means of relative risk, odds ratio, weighted mean difference 95% confidence interval. The effectiveness of LGG in gastrointestinal infections and diarrhea, antibiotic and Clostridium difficile associated diarrhea, irritable bowel syndrome, inflammatory bowel disease, respiratory tract infections, allergy, cardiovascular diseases, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, cystic fibrosis, cancer, elderly end sport were analyzed.
A single intravesical instillation of Lactobacillus rhamnosus GG is safe in children and adults with neuropathic bladder: A phase Ia clinical trial. [2022]Context/objective: Manipulation of the microbiome is an emerging approach to promote health. We conducted a Phase Ia safety study of a single bladder instillation of probiotics in asymptomatic patients with neuropathic bladder to determine the tolerability and safety of a single Lactobacillus instillation.Design: Phase Ia safety study.Setting: Outpatient rehabilitation clinic at a rehabilitation hospital (adults) and urology clinic at a free-standing children's hospital (children).Participants: Ten patients with neuropathic bladder were included: five children with spina bifida and five adults with spinal cord injury.Interventions: A single Lactobacillus rhamnosus GG (Culturelle, 20 billion live organisms) instillation.Outcome measures: After the instillation, participants self-monitored symptoms using the Urinary Symptoms Questionnaire for People with Neuropathic Bladder using Intermittent Catheterization daily for one week. Repeat urinalysis, urine culture, and 16S bacterial rRNA-based microbiome analyses were performed 7-10 days after instillation.Results: Probiotic instillation was well-tolerated. One child had upper respiratory tract symptoms during the trial, and two had transient cloudy urine. No adults reported any symptoms following instillation. Lactobacillus did not grow on culture post-instillation. There were differences in beta diversity of the urine microbiome in children vs. adults with neuropathic bladder (P < 0.0156). Lactobacillus was present in the pre-instillation urinary microbiomes all of the adults and 4 out of 5 of the pediatric subjects, and identified in 4 out of 5 of both the adult and pediatric subjects' post-instillation urinary microbiomes.Conclusion: Intravesical instillation of Culturelle probiotic may be safe and well-tolerated in patients with neuropathic bladder.
Intravesical Lactobacillus rhamnosus GG is safe and well tolerated in adults and children with neurogenic lower urinary tract dysfunction: first-in-human trial. [2023]Label="BACKGROUND" NlmCategory="BACKGROUND">Urinary symptoms are common for people with neurogenic lower urinary tract dysfunction (NLUTD). No nonprescription approach has been proven safe and effective for self-management of urinary symptoms. Our objective was to describe the safety and tolerability of Lactobacillus rhamnosus GG (LGG®) instilled intravesically for self-management of inflammatory urinary symptoms in adults and children with NLUTD due to spinal cord injury or disease (SCI/D) and who use intermittent catheterization (IC).
Effects of Intravesical Lactobacillus Rhamnosus GG on Urinary Symptom Burden in People with Neurogenic Lower Urinary Tract Dysfunction. [2022]To test the effectiveness of intravesical Lactobacillus rhamnosus GG (LGG) to reduce the burden of urinary symptoms for individuals with spinal cord injury and disease (SCI/D) with neurogenic lower urinary tract dysfunction (NLUTD) who manage their bladders with intermittent catheterization (IC).