Ignite Creation Date:
2024-05-06 @ 2:25 AM
Last Modification Date:
2024-10-26 @ 11:18 AM
Study NCT ID:
NCT02044965
Status:
UNKNOWN
Last Update Posted:
2021-09-09
First Post:
2014-01-17
Brief Title:
Can Probiotics be Used in the Prevention of Recurrent UTI in Paediatric Neurogenic Bladder
Sponsor:
London Health Sciences Centre
Organization:
London Health Sciences Centre
Study Overview
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
Status:
UNKNOWN
Status Verified Date:
2021-09
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
Detailed Description:
From Dr Daves practice 53 suitable patients who are using CIC to manage NB disease and are receiving long term low-dose antibiotic prophylaxis designed to prevent RUTI have been identified
On average another 5 eligible patients would be expected within a six- month window From this pool the study will enroll 36 adolescents 12 years of age They will have had a history of RUTI over the past 12 months and will have been receiving chemoprophylaxis for at least one month The study design and reporting will conform to the CONSORT guidelines
Patients will be enrolled after informed consent and the baseline evaluation will include a history and physical examination and verification of previous culture proven UTI A urine sample will be obtained using clean catheterization and subjected to urinalysis microbiome metabolome bacteriological culture and antibiotic resistance assessment and assayed for markers for inflammation A stool sample will also be collected to analyse the gut microbiota and drug resistance profiles of E coli Each patient will receive counselling at baseline and at 3 months follow up on ensuring adequate fluid intake proper clean intermittent catheterization technique and frequency and over the- counter treatment for constipation Post catheterization bladder scans will be performed to ensure completeness of bladder emptying Baseline bladder and renal function will be assessed
Investigators expect interest from the patientsparents in their practice as at the very least the study will entail a check-up of how their condition is being managed and for us to be able to provide them with additional information on their microbiota in urine and stool Thus patients who do not wish to be randomized to receive probiotics or change to a probiotic regimen can still be included as a control group remaining on prophylaxis 12 subjects Investigators would expect their bacterial drug resistance profiles and intestinal side effects to remain unchanged for the next six months For 24 subjects interested in being considered for a different approach to their care they will be randomized using a computer generated randomization sequence with balanced block randomization block size 4 pre generated and allocation performed using sealed envelopes and a third party to preserve allocation concealment from the recruiting physician A 1 1 allotment will be performed to the 2 study groups 12 patients will continue antibiotic prophylaxis but also receive daily probiotic capsules and the other 12 will be randomized to receive probiotics and a drug placebo for six months after a washout period of 1 week Patient and parent blinding will be partially achieved by each patient taking two pills each day with the placebo pill or capsule resembling the active product The placebo drug used will be a similar appearance sugar based pill with no active ingredient The probiotic capsule will contain only food grade excipients present in the probiotic capsule Patients will be supplied with their pills and capsules for 3- month duration
In addition the laboratory technician and outcome assessor data entry and analysis will be blinded to patient allotment Antibiotic prophylaxis will consist of Septra trimethoprim 2 mgkg sulfamethoxazole for the 12 controls or 12 randomized to antibiotic and probiotic arm Probiotic therapy will comprise of two capsules of RePhResh Pro-B approved by Health Canada and sold at Shoppers Drug Mart in Canada which consists of 5 billion total organisms of L rhamnosus GR-1 and L reuteri RC-14 per capsule The capsule can be added to milk or orange juice if the patient is unable to swallow it All 36 patientsparents will be asked to keep a diary to record use of medications OTC medications for colds flu others and will be asked not to take any probiotic products including probiotic yogurt during the study duration In addition patients will fill out a questionnaire each week study duration is 6 months after the first baseline visit is conducted to assess a range of potential adverse events such as constipation diarrhea bloating nausea pain fever on a scale of 1-10 At the three month follow-up compliance will be assessed by return of the empty product containers and review of the diary A second course of three month treatment will then be provided At three and six months clinical assessment urine and stool samples will be provided
At 6 month follow-up patients will receive a renal ultrasound to assess the health of the upper renal tract as well as a post-catheterization bladder scan an cystometry During the study any patient with two or more episodes of UTI will be treated with an alternative antibiotic prophylactic regimen
On average another 5 eligible patients would be expected within a six- month window From this pool the study will enroll 36 adolescents 12 years of age They will have had a history of RUTI over the past 12 months and will have been receiving chemoprophylaxis for at least one month The study design and reporting will conform to the CONSORT guidelines
Patients will be enrolled after informed consent and the baseline evaluation will include a history and physical examination and verification of previous culture proven UTI A urine sample will be obtained using clean catheterization and subjected to urinalysis microbiome metabolome bacteriological culture and antibiotic resistance assessment and assayed for markers for inflammation A stool sample will also be collected to analyse the gut microbiota and drug resistance profiles of E coli Each patient will receive counselling at baseline and at 3 months follow up on ensuring adequate fluid intake proper clean intermittent catheterization technique and frequency and over the- counter treatment for constipation Post catheterization bladder scans will be performed to ensure completeness of bladder emptying Baseline bladder and renal function will be assessed
Investigators expect interest from the patientsparents in their practice as at the very least the study will entail a check-up of how their condition is being managed and for us to be able to provide them with additional information on their microbiota in urine and stool Thus patients who do not wish to be randomized to receive probiotics or change to a probiotic regimen can still be included as a control group remaining on prophylaxis 12 subjects Investigators would expect their bacterial drug resistance profiles and intestinal side effects to remain unchanged for the next six months For 24 subjects interested in being considered for a different approach to their care they will be randomized using a computer generated randomization sequence with balanced block randomization block size 4 pre generated and allocation performed using sealed envelopes and a third party to preserve allocation concealment from the recruiting physician A 1 1 allotment will be performed to the 2 study groups 12 patients will continue antibiotic prophylaxis but also receive daily probiotic capsules and the other 12 will be randomized to receive probiotics and a drug placebo for six months after a washout period of 1 week Patient and parent blinding will be partially achieved by each patient taking two pills each day with the placebo pill or capsule resembling the active product The placebo drug used will be a similar appearance sugar based pill with no active ingredient The probiotic capsule will contain only food grade excipients present in the probiotic capsule Patients will be supplied with their pills and capsules for 3- month duration
In addition the laboratory technician and outcome assessor data entry and analysis will be blinded to patient allotment Antibiotic prophylaxis will consist of Septra trimethoprim 2 mgkg sulfamethoxazole for the 12 controls or 12 randomized to antibiotic and probiotic arm Probiotic therapy will comprise of two capsules of RePhResh Pro-B approved by Health Canada and sold at Shoppers Drug Mart in Canada which consists of 5 billion total organisms of L rhamnosus GR-1 and L reuteri RC-14 per capsule The capsule can be added to milk or orange juice if the patient is unable to swallow it All 36 patientsparents will be asked to keep a diary to record use of medications OTC medications for colds flu others and will be asked not to take any probiotic products including probiotic yogurt during the study duration In addition patients will fill out a questionnaire each week study duration is 6 months after the first baseline visit is conducted to assess a range of potential adverse events such as constipation diarrhea bloating nausea pain fever on a scale of 1-10 At the three month follow-up compliance will be assessed by return of the empty product containers and review of the diary A second course of three month treatment will then be provided At three and six months clinical assessment urine and stool samples will be provided
At 6 month follow-up patients will receive a renal ultrasound to assess the health of the upper renal tract as well as a post-catheterization bladder scan an cystometry During the study any patient with two or more episodes of UTI will be treated with an alternative antibiotic prophylactic regimen
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None