Identification of Predictive Blood Biomarkers of Recurrent Urinary Tract Infections

Study Overview
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Brief Summary
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Urinary tract infections affect more than 130 million people worldwide each year. Almost 50% of women will have at least one urinary tract infection during their lifetime, usually cystitis. Half of them will have recurrent cystitis. Antibiotics are the first-line treatment for cystitis, but their effectiveness is decreasing due to the rapid spread of multi-resistant uro-pathogenic bacteria. The objective of this study is to identify blood biomarkers associated with a high risk of recurrent cystitis. Immune system cells, and more specifically innate immunity cells, play a key role in controlling urinary tract infections. In addition, clinical studies have shown that there is a high inter-individual variability in the ability of innate immune cells to respond to different stimuli. We therefore hypothesized that there was an association between the risk of recurrent cystitis and a deficiency of certain immune cell types in producing certain pro-inflammatory cytokines, including TNF-α, in response to one or more bacterial stimuli, particularly flagellin.

Official Title
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Identification of Predictive Blood Biomarkers of Recurrent Urinary Tract Infections

Conditions
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Urinary Tract Infections

Intervention / Treatment
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* Procedure: Collection of blood samples
* Other: Collection of fecal samples
* Other: Collection of urine samples
* Other: Collection of vaginal swaps


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female aged 18 to 28 years; Subject accepting to be serologically tested for HIV and HCV; Subject considered healthy by the physician on the basis of medical history and clinical examination; Subject with a body mass index between 18.5 and 30 kg/m2; Subject understands and speaks French and is able to give written consent; Subject affiliated to Social Security or a similar regime; Having reported a single cystitis since the age of 14 (Group 1), or 3 or more cystitis over a 12-month period since the age of 14 (Group 2). Exclusion Criteria: Subject protected by law under guardianship or curatorship, or unable to participate in a clinical study under Article L. 1121-16 of the French Public Health Code; Subject who has participated in a clinical research study in the last 3 months in which he/she was exposed to a pharmaceutical product or medical device; Subject who has stayed in a tropical or subtropical country in the last 3 months; Pregnant or breastfeeding subject for women of childbearing age; Subject with special diet for medical reasons and prescribed by a doctor or dietician (e.g. a low-calorie diet or a diet intended to lower cholesterol levels); Subject who regularly consumes large quantities of alcohol, i. e. more than 50 g of pure alcohol per day (e. g. more than 4 glasses of 150 ml wine, more than 4 pints of 250 ml beer, or more than 4 glasses of 40 ml containing strong alcohol); Subject who has used an illegal recreational drug in the past 3 months; Subject who has taken an immunosuppressive or immunomodulatory drug (excluding intranasally or topically administered corticosteroids) in the past 2 weeks, or for more than 14 consecutive days in the past 6 months; Subject who has been vaccinated within the last 3 months; Subject who received a blood transfusion or immunoglobulins in the last 3 months; Subject stating that he has not been fasting for at least 10 hours; Subject reporting HIV or HCV status; Subject who had an infectious episode or was treated with antibiotics during the 4 weeks prior to the visit; Subject with a positive urinary pregnancy test; Subject with a severe and/or chronic and/or recurrent pathology, in particular: A chronic inflammatory and/or autoimmune or allergic disease and in particular a chronic inflammatory disease of the intestine (Crohn's disease, ulcerative colitis), epidermis (psoriasis, atopic dermatitis), joints (rheumatoid arthritis), nervous system (multiple sclerosis), type I diabetes; High blood pressure or type II diabetes; A neurodegenerative disease. Subject who has been diagnosed with cancer and has not been in remission for more than 5 years.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 28 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: No recurrent UTI<br>Healthy female volunteer aged 18 to 28 years reporting a single cystitis since the age of 14 years | Procedure: Collection of blood samples<br>* 23 mL of blood will be collected during the inclusion visit<br>Other: Collection of fecal samples<br>* Fecal sample self-collected after the inclusion visit<br>Other: Collection of urine samples<br>* 10 mL of urine will be collected during the inclusion visit<br>Other: Collection of vaginal swaps<br>* Sample of vaginal microbiota collected during the inclusion visit<br>|
| Experimental: Recurrent UTI<br> | Procedure: Collection of blood samples<br>* 23 mL of blood will be collected during the inclusion visit<br>Other: Collection of fecal samples<br>* Fecal sample self-collected after the inclusion visit<br>Other: Collection of urine samples<br>* 10 mL of urine will be collected during the inclusion visit<br>Other: Collection of vaginal swaps<br>* Sample of vaginal microbiota collected during the inclusion visit<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TNF-α measurement in blood cell culture media using Luminex® technology. | The concentrations of TNF-α will be expressed in ng/ml by calibration with a standard range. | At 18 months |