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Can Probiotics be Used in the Prevention of Recurrent UTI in Paediatric Neurogenic Bladder

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ClinicalTrials.gov Identifier: NCT02044965
Recruitment Status : Unknown
Verified March 2015 by Dr. Sumit Dave, London Health Sciences Centre.
Recruitment status was:  Not yet recruiting
First Posted : January 24, 2014
Last Update Posted : March 6, 2015
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:

Although clean intermittent catheterization (CIC) remains the mainstay to ensure complete low-pressure bladder emptying in neurogenic bladder (NB) patients, this forms a vehicle for bacterial entry and colonization of the urinary tract, which can lead to recurrent urinary tract infection (RUTI) and renal damage. Up to 25% of NB patients on CIC suffer from RUTI and daily, low-dose antibiotic prophylaxis is widely prescribed to prevent these infections. Unfortunately, this therapeutic option is not evidence-based and can be associated with a higher risk of RUTI secondary to development of antibiotic resistance. In addition, many children suffer from a range of adverse reactions and emergence of drug resistant organisms. Moreover, recent studies have shown that antibiotics cause a major disruption in the human microbiome, potentially leading to long term major problems.

Probiotics are live microorganisms, which when administered in adequate amounts confer a health benefit on the host. There is evidence that probiotics restore microbial homeostasis in the vagina, reduce the risk of pathogen ascension into the bladder, and modulate immunity to better protect the host. Probiotic strains, including Lactobacillus rhamnosus GR-1, Lactobacillus reuteri B-54 and RC-14, have been shown to be safe and efficacious in an oral formulation or as a vaginal suppository in improving the microbiota profile of the vagina and decreasing the risk of RUTI. Various mechanisms appear to be involved, including modulating antimicrobial and inflammatory defenses, up-regulating protective mucin production and reducing the pressure on pathogens to acquire antibiotic resistance genes. A randomized trial comparing probiotics to antibiotic prophylaxis in children with vesicoureteric reflux showed equivalent reduction in the incidence of RUTI and development of new renal scarring. In addition, down regulation of inflammatory cytokines can potentially favorably alter bladder function and prevent bladder fibrosis.

Investigators at London Health Sciences Centre (LHSC) have the opportunity to acquire clinical data that would strengthen the case for probiotics to be integrated into pediatric urology practice for managing CIC and RUTI. This would be the first such study in pediatric NB patients.

The main objective of this study is to determine whether the use of probiotics (lactobacilli) can decrease the impact of adverse side effects and the antibiotic resistance that is seen with the prolonged use of antibiotics for patients with neurogenic bladder conditions.


Condition or disease Intervention/treatment Phase
Urinary Tract Infection Other: Antibiotic Drug: Probiotic Phase 1 Phase 2

  Show Detailed Description

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Clinical Trial to Determine the Extent to Which Probiotic Therapy Reduces Side Effects of Antibiotic Prophylaxis in Pediatric Neurogenic Bladder Patients With a History of Recurrent Urinary Tract Infections
Study Start Date : January 2015
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
No Intervention: Antibiotic
This group will be prescribed a dose of antibiotics (Septra 2mg/kg)
Placebo Comparator: Probiotic plus placebo
Receive probiotic plus an antibiotic placebo
Other: Antibiotic
2 mg/kg per day via oral ingestion.
Other Name: Trimethoprim sulfamethoxazole (Septra)
Drug: Probiotic
2 capsules; 5 billion total organisms of L. rhamnosus GR-1 and L. reuteri RC-14 per capsule
Other Name: L. rhamnosus GR-1 and L. reuteri RC-14
Active Comparator: probiotics plus antibiotic
This group will be on a dose of probiotics (2 capsules; 5 billion total organisms of L. rhamnosus GR-1 and L. reuteri RC-14 per capsule) plus a antibiotic (Septra)
Other: Antibiotic
2 mg/kg per day via oral ingestion.
Other Name: Trimethoprim sulfamethoxazole (Septra)
Drug: Probiotic
2 capsules; 5 billion total organisms of L. rhamnosus GR-1 and L. reuteri RC-14 per capsule
Other Name: L. rhamnosus GR-1 and L. reuteri RC-14


Outcome Measures

Primary Outcome Measures :
  1. Side effects [ Time Frame: Once a week for the duration of the study. The length of the study will be 6 months from the first baseline visit after the patient has been enrolled in the study and the first dispense of the study drug has been completed. ]
    Use a questionnaire to assess frequency and type of side effect while on prophylactic antibiotic, antibiotic plus probiotic or probiotic plus placebo


Secondary Outcome Measures :
  1. Mean number of recurrent urinary tract infection episodes [ Time Frame: Over the 6 months follow up ]
    Mean number of RUTI episodes (>105 colony forming unit (CFU)/mL from a catheter specimen, with leukocyturia (>10/HPF) and the presence of symptoms and signs such as fever (>38.5°C), flank pain or suprapubic pain) during a 6 month follow-up period.

  2. Time to first urinary tract infection [ Time Frame: Over 6 months follow up ]
    the time it takes for a study subject to develop a urinary tract infection

  3. Changes in pro-inflammatory cytokines [ Time Frame: At baseline, 3 and 6 months ]
    Changes in pro-inflammatory cytokines (IL-6, TNF (tumor necrosis factor)-α) and pro-inflammatory chemokine (IL-8) associated with inflammation and immune cell recruitment. Urinary levels of each factor will be measured using multiplexed immunoassay kits employing Luminex® xMAP fluorescent bead-based technology (Luminex Corporation, Austin, TX) and the Bio-Plex 200 readout system (Bio- Rad Laboratories Inc., Hercules, California.

  4. Changes in metabolomic profiles of urine [ Time Frame: Baseline, 3 and 6 months ]
    Changes in metabolomic profiles of urine, as measured by Gas chromatography mass spectrometry (GS-MS) and nuclear magnetic resonance (NMR)

  5. Bladder storage function [ Time Frame: Baseline, 6 months ]
    Bladder storage function (capacity, compliance, overactivity).


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • - Patients will have had a history of recurrent urinary tract infections over the past 12 months.
  • Patients will have been receiving chemoprophylaxis for at least one month.
  • Patients who are using clean intermittent catheterization to manage a neurogenic bladder condition.
  • PATIENTS WILL BE BETWEEN THE AGES OF 6-20.

Exclusion Criteria:

  • Patient has a known allergy to Septra
  • Patients pregnant or nursing will be excluded.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02044965


Contacts
Contact: Sumit Dave 519-685-8439 sumit.dave@lhsc.on.ca

Locations
Canada, Ontario
London Health Sciences Centre Not yet recruiting
London, Ontario, Canada, N6A 4G5
Contact: Lee-Anne Fochesato    5196858500 ext 56366    leeanne.fochesato@lhsc.on.ca   
Principal Investigator: Sumit Dave         
Sponsors and Collaborators
London Health Sciences Centre
Canadian Urological Association
Investigators
Principal Investigator: Sumit Dave London Health Sciences Centre
More Information

Responsible Party: Dr. Sumit Dave, Assistant Professor, Pediatric Urologist, London Health Sciences Centre
ClinicalTrials.gov Identifier: NCT02044965     History of Changes
Other Study ID Numbers: LHSC - AP 1
First Posted: January 24, 2014    Key Record Dates
Last Update Posted: March 6, 2015
Last Verified: March 2015

Keywords provided by Dr. Sumit Dave, London Health Sciences Centre:
urinary tract infection
antibiotic prophylaxis
probiotics
neurogenic bladder
clean intermittent catheterization

Additional relevant MeSH terms:
Infection
Urinary Tract Infections
Urinary Bladder, Neurogenic
Urologic Diseases
Neurologic Manifestations
Nervous System Diseases
Urinary Bladder Diseases
Signs and Symptoms
Anti-Bacterial Agents
Trimethoprim, Sulfamethoxazole Drug Combination
Antibiotics, Antitubercular
Trimethoprim
Sulfamethoxazole
Anti-Infective Agents
Antitubercular Agents
Anti-Infective Agents, Urinary
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP2C8 Inhibitors
Cytochrome P-450 Enzyme Inhibitors