Effect of a Probiotic on the Urinary Tract Microbiota of Participants With Recurrent Urinary Tract Infection.

Study Overview
=================
Brief Summary
-----------------
Urinary tract infections (UTIs) are the most common bacterial infections in women. 50% of women experiencing at least one UTI in their lifetime with an annual prevalence of 0.5-0.7%. An interventional, randomized, double-blind, placebo-controlled study will be conducted to investigate the effect of a probiotic strains on the urinary tract microbiota in participants with recurrent urinary tract infection (rUTI). The study duration will be 6 and a half months, including 6 months product intake. Participants will be randomly assigned to one of the three study groups: control group with placebo administration, probiotic administration group (1 dose) and probiotic administration group (2 doses).

Official Title
-----------------
Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of a Probiotic on the Urinary Tract Microbiota in Women With Recurrent Urinary Tract Infections (rUTI).

Conditions
-----------------
Recurrent Urinary Tract Infection

Intervention / Treatment
-----------------
* Dietary Supplement: Probiotic
* Dietary Supplement: Probiotic + placebo
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult women with aged between 18 and 50 years old, diagnosed with recurrent UTI (defined as at least two episodes during the last six months or three during the last 12 months). Diagnosed, the last 72 hours, for a new UTI episode. Written informed consent signed. Exclusion Criteria: Menopausal Pregnant, breastfeeding or planning to become pregnant during the study. Congenital abnormalities of the urinary tract. Renal functional alterations, such as neurogenic bladder or vesicoureteral reflux. Relevant renal disorders, such as interstitial cystitis, renal lithiasis, renal failure, kidney transplantation, pyelonephritis, renal nephropathy, etc. Permanent catheter. Immunocompromised (eg: cancer and/or transplant, patients who are taking immunosuppressive drugs, patients with hereditary diseases that affect or may affect the immune system). Type I diabetes. With a defect in the intestinal epithelium barrier (eg: chronic diarrhea, inflammatory bowel disease). Heart failure and cardiac medical history (eg, artificial heart valve, medical history of infective endocarditis, rheumatic fever, or cardiac malformation). Under antibiotics prophylactic treatment without willingness to leave it at the time of inclusion. Probiotics supplementation during the previous 2 weeks. To have received Urovac, Uro-Vaxom or equivalent vaccine during the last year. Currently participating in another clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Probiotic<br>2 Capsule daily containing approximately 1*10E9 colony forming unit (CFU) of Lactobacillus CECT 9422 +1*10E9 colony forming unit (CFU) of Bifidobacterium CECT 30257. | Dietary Supplement: Probiotic<br>* 1 capsule of probiotic (Lactobacillus CECT 9422 + Bifidobacterium CECT 30257) every 12 hours for 6-months.<br>|
| Active Comparator: Probiotic + placebo<br>One capsule daily containing approximately 1*10E9 colony forming unit (CFU) of Lactobacillus CECT 9422 +1*10E9 colony forming unit (CFU) of Bifidobacterium CECT 30257 and 1 capsule of placebo supplement. | Dietary Supplement: Probiotic + placebo<br>* 1 capsule of probiotic + 1 capsule of placebo per day for 6-months.<br>|
| Placebo Comparator: Placebo<br>Two capsules daily of Placebo supplement. | Dietary Supplement: Placebo<br>* 1 capsule of placebo every 12 hours for 6-months.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the number of participants with a positive urine culture | The number of participants with a positive urine culture will be compared between groups of treatment. | Before intervention | 
| Evaluate the number of participants with a positive urine culture | The number of participants with a positive urine culture will be compared between groups of treatment. | After 3 months of intervention. | 
| Evaluate the number of participants with a positive urine culture | The number of participants with a positive urine culture will be compared between groups of treatment. | After 6 months of intervention. | 
| Evaluate the total bacterial count in urine samples. | The total bacterial count in urine samples will be compared between groups of treatment. | Before intervention | 
| Evaluate the total bacterial count in urine samples. | The total bacterial count in urine samples will be compared between groups of treatment. | After 3 months of intervention | 
| Evaluate the total bacterial count in urine samples. | The total bacterial count in urine samples will be compared between groups of treatment. | After 6 months of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of UTI episodes |  | After 3 and 6 months of intervention. | 
| Infection free participants (%) |  | After 6 months of intervention. | 
| Elapsed time until the 1st episode of UTI. |  | After 6 months of intervention. | 
| Elapsed time between the 1st and 2nd episode of UTI. |  | After 6 months of intervention. | 
| Elapsed time between the 2nd and 3rd episode of UTI. |  | After 6 months of intervention. | 
| Duration of UTI episodes. |  | After 6 months of intervention. | 
| The number of participants which associate sexual activity with the UTI episodes | The number of participants which associate sexual activity with the apperance of an UTI episode will be counted and compared between groups. | After 6 months of intervention. | 
| Number of present symptoms during new UTI episodes. |  | After 6 months of intervention. | 
| Number of participants with dysuria. |  | After 6 months of intervention. | 
| Duration of dysuria. |  | After 6 months of intervention. | 
| Number of participants with pollakiuria |  | After 6 months of intervention. | 
| Duration of pollakiuria |  | After 6 months of intervention. | 
| Number of participants with urinary urgency. |  | After 6 months of intervention. | 
| Duration of urinary urgency. |  | After 6 months of intervention. | 
| Number of participants with tenesmus. |  | After 6 months of intervention. | 
| Duration of tenesmus. |  | After 6 months of intervention. | 
| Number of participants with hematuria. |  | After 6 months of intervention. | 
| Duration of hematuria |  | After 6 months of intervention. | 
| Number of participants with dyspareunia |  | After 6 months of intervention. | 
| Duration of dyspareunia |  | After 6 months of intervention. | 
| Number of participants with pelvic pain |  | After 6 months of intervention. | 
| Duration of pelvic pain |  | After 6 months of intervention. | 
| Number of participants with fever (Tª ≥ 38ºC). |  | After 6 months of intervention. | 
| Duration of fever (Tª ≥ 38ºC). |  | After 6 months of intervention. | 
| Number of participants with cloudy and smelly urine |  | After 6 months of intervention. | 
| Duration of cloudy and smelly urine |  | After 6 months of intervention. | 
| Number of antibiotics administered for the UTI episode. |  | After 6 months of intervention. | 
| Duration of antibiotic treatment for the UTI episode. |  | After 6 months of intervention. | 
| Number of antibiotic treatments administered during new UTI episodes. |  | After 6 months of intervention. | 
| Duration of antibiotic treatments administered during new UTI episodes. |  | After 6 months of intervention. | 
| Microbiome composition of stool samples determined by 16S sequencing. | The composition of fecal microbiome will be compared between treatments group and time | After 6 months of intervention. | 
| Microbiota composition of urine samples determined by culture techniques. | The composition of urine microbiota will be compared between treatments group and time. | After 6 months of intervention. | 
| Metabolomic profile of urine samples. |  | After 6 months of intervention. |