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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2014 by London Health Sciences Centre
Sponsor:
Collaborator:
Canadian Urological Association
Information provided by (Responsible Party):
Dr. Sumit Dave, London Health Sciences Centre
ClinicalTrials.gov Identifier:
NCT02044965
First received: January 17, 2014
Last updated: January 22, 2014
Last verified: January 2014
  Purpose

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 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 Intervention Phase
Urinary Tract Infection
Other: Antibiotic
Drug: Probiotic
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by London Health Sciences Centre:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
    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:
  • Mean number of recurrent urinary tract infection episodes [ Time Frame: Over the 6 months follow up ] [ Designated as safety issue: No ]
    Mean number of RUTI episodes (>105 CFU/mL from a catheter specimen, with leukocytouria (>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.

  • Time to first urinary tract infection [ Time Frame: Over 6 months follow up ] [ Designated as safety issue: No ]
    the time it takes for a study subject to develop a urinary tract infection

  • Changes in pro-inflammatory cytokines [ Time Frame: At baseline, 3 and 6 months ] [ Designated as safety issue: No ]
    Changes in pro-inflammatory cytokines (IL-6, TNF-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 beadbased technology (Luminex Corporation, Austin, TX) and the Bio-Plex 200 readout system (Bio- Rad Laboratories Inc., Hercules, CA.

  • Changes in metabolomic profiles of urine [ Time Frame: Baseline, 3 and 6 months ] [ Designated as safety issue: No ]
    Changes in metabolomic profiles of urine, as measured by Gas chromatography mass spectrometry (GS-MS) and nuclear magnetic resonance (NMR)

  • Bladder storage function [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    Bladder storage function (capacity, compliance, overactivity) as determined by urodynamic study.


Estimated Enrollment: 36
Study Start Date: February 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   12 Years to 17 Years
Genders Eligible for Study:   Both
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 (with either trimethoprim-sulfamethoxazole or nitrofurantoin) 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 12-17.

Exclusion Criteria:

  • - Patients with vesicoureteral reflux will be excluded from the study.
  • Patients pregnant or nursing will be excluded.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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

No publications provided

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
Study First Received: January 17, 2014
Last Updated: January 22, 2014
Health Authority: Canada: Ethics Review Committee

Keywords provided by London Health Sciences Centre:
urinary tract infection
antibiotic prophylaxis
probiotics
neurogenic bladder
clean intermittent catheterization

Additional relevant MeSH terms:
Urinary Bladder, Neurogenic
Urinary Tract Infections
Neurologic Manifestations
Nervous System Diseases
Urinary Bladder Diseases
Urologic Diseases
Signs and Symptoms
Infection
Anti-Bacterial Agents
Antibiotics, Antitubercular
Sulfamethoxazole
Trimethoprim-Sulfamethoxazole Combination
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Anti-Infective Agents, Urinary
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on July 22, 2014