Identification of Predictive Blood Biomarkers of Recurrent Urinary Tract Infections (Predict-UTI)

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.

Study Overview

• Status: Completed
• Conditions: Urinary Tract Infections
• Intervention / Treatment: Procedure: Collection of blood samples; Other: Collection of fecal samples; Other: Collection of urine samples; Other: Collection of vaginal swaps

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Nice, France, 06200
    • Hôpital de l'Archet 1 - CHU de Nice - Service d'Infectiologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 28 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2019
• Primary Completion (Actual): December 3, 2023
• Study Completion (Actual): December 7, 2023

Study Registration Dates

• First Submitted: January 25, 2019
• First Submitted That Met QC Criteria: January 25, 2019
• First Posted (Actual): January 28, 2019

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Infections; Communicable Diseases; Urinary Tract Infections
• Other Study ID Numbers: 18-PP-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No