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

NCT02044965 | Unknown Phase 1

• 1 other identifier: LHSC - AP 1
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Urinary Tract Infection

Keywords

urinary tract infection; antibiotic prophylaxis; probiotics; neurogenic bladder; clean intermittent catheterization

Outcome Measures

Primary Outcomes (1)

• Side effects

  Use a questionnaire to assess frequency and type of side effect while on prophylactic antibiotic, antibiotic plus probiotic or probiotic plus placebo

  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.

Secondary Outcomes (5)

• Mean number of recurrent urinary tract infection episodes

  Over the 6 months follow up

• Time to first urinary tract infection

  Over 6 months follow up

• Changes in pro-inflammatory cytokines

  At baseline, 3 and 6 months

• Changes in metabolomic profiles of urine

  Baseline, 3 and 6 months

• Bladder storage function

  Baseline, 6 months

Study Arms (3)

Antibiotic

NO INTERVENTION

This group will be prescribed a dose of antibiotics (Septra 2mg/kg)

Probiotic plus placebo

PLACEBO COMPARATOR

Receive probiotic plus an antibiotic placebo

Other: Antibiotic; Drug: Probiotic

probiotics plus antibiotic

ACTIVE COMPARATOR

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; Drug: Probiotic

Interventions

Antibiotic OTHER

2 mg/kg per day via oral ingestion.

Also known as: Trimethoprim sulfamethoxazole (Septra)

Probiotic plus placebo; probiotics plus antibiotic

Probiotic DRUG

2 capsules; 5 billion total organisms of L. rhamnosus GR-1 and L. reuteri RC-14 per capsule

Also known as: L. rhamnosus GR-1 and L. reuteri RC-14

Probiotic plus placebo; probiotics plus antibiotic

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \- 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.

You may not qualify if:

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

Sponsors & Collaborators

• London Health Sciences Centre: lead
• Canadian Urological Association: collaborator

Study Sites (1)

London Health Sciences Centre

London, Ontario, N6A 4G5, Canada

RECRUITING

MeSH Terms

Conditions

Urinary Tract Infections; Urinary Bladder, Neurogenic

Interventions

Anti-Bacterial Agents; Trimethoprim, Sulfamethoxazole Drug Combination; Probiotics

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Neurologic Manifestations; Nervous System Diseases; Urinary Bladder Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Sumit Dave

  London Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sumit Dave

CONTACT

519-685-8439; sumit.dave@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Pediatric Urologist

Study Record Dates

• First Submitted: January 17, 2014
• First Posted: January 24, 2014
• Study Start: January 1, 2015
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2023
• Last Updated: September 9, 2021

Record last verified: 2021-09

Locations

CA (1)