Controlled Human Urine Transfusion for UTI

Study Overview
=================
Brief Summary
-----------------
The primary objective of this pilot study is to investigate the safety and tolerability of controlled human urine transfusion in female patients with recurrent UTI's. Seconday and exploratory objectives are to evaluate the diversity of the urine microbiome after urine transfusion, to assess the longevity of changes in the urine microbiome in patients after urine transfusion over a period of 6 months and to assess the frequency of UTI's after the transfusion.

Detailed Description
-----------------
Recurrent urinary tract infections (UTIs) are the most common bacterial infections in nursing homes, in acute care and the general practice. Increasing antibiotic resistance of enterobacteriaciae poses a challenge to the treatment of UTIs. Unlike previously thought, the bladder is colonized with bacteria, which together form the urine microbiome. Recurrent urinary tract infections are associated with a decreased urinary microbiota diversity, potentially making recolonization by bacterial interference in the bladder an alternative therapy for UTI. Pioneering studies showed that local bacterial interference in the bladder can be performed safely and has potential as prophylactic intervention. We now propose to expand this bacterial interference to a polymicrobial inoculum to increase adherence of the donor microbiome and as such expand the prophylactic effect. This pilot trial will investigate the safety and tolerability of urine transfusion from healthy donors to the bladders of patients with recurrent UTIs. The primary objective of this pilot study is to investigate the safety and tolerability of controlled human urine transfusion in female patients with recurrent UTI's. Secondary and exploratory objectives are to evaluate the diversity of the urine microbiome after urine transfusion, to assess the longevity of changes in the urine microbiome in patients after urine transfusion over a period of 6 months and to assess the frequency of UTI's after the transfusion.

Official Title
-----------------
Safety and Tolerability of Controlled Human Urine Transfusion for Urinary Tract Infection Prevention (SHUTUP): a Pilot Study

Conditions
-----------------
Recurrent Urinary Tract Infection, Safety Issues

Intervention / Treatment
-----------------
* Procedure: urine transfusion


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is premenopausal, aged ≥ 18 and ≤45 years Subject had recurrent UTI's (≥3 documented UTI's in the last year with documented symptom-free interval of at least 2 weeks) following the definition of a urinary tract infection: the presence of significance bacteruria (10^3 CFU/ml or more), pyuria and fever plus one or more of the following signs and symptoms: suprapubic or flank discomfort, dysuria, bladder spasms or pollakiuria Subject has a documented urinary tract infection (see definition), for which oral antibiotic therapy has been initiated. Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby. Subject is able to communicate well with the investigators and is available to attend all study visits. Subject has signed informed consent. Subject will remain available during the first 3 weeks of the study period (recruiting, intervention and first follow-up). Exclusion Criteria: Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, immune-deficient, psychiatric and other disorders, which could compromise the health of the recipient during the study. These include, but are not limited to, any of the following: positive HIV, HBV or HCV screening tests; the use of immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period. Documented vesico-urethral reflux Documented urinary retention > 100 milliliters post-void residual urine Anatomic urogenital abnormalities Urolithiasis Nephrostomy catheters Extra-urogenital infections that require prolonged antibiotic therapy Pregnancy Use of probiotics and or cranberry juice Allergy or intolerance for multiple common prescribed antibiotics Carriage of multi drug resistant organisms in faeces and/or urine without regular antibiotic treatment options

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

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

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

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

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: prospective, open label pilot clinical trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Urine transfusion<br>Intervention: Two transfusions of 100 ml of urine within 5 days by transurethral catheterization after an antibiotic free interval of 3 days. | Procedure: urine transfusion<br>* Two transfusions of 100 ml of urine within 5 days by transurethral catheterization after an antibiotic free interval of 3 days.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | The cumulative number of possibly, probably or definitely related adverse events within 6 months of controlled human urine transfusion | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diversity of the urine microbiome after urine transfusion | Change in Shannon diversity index of the bladder microbiome before and after urine transfusion | 6 months | 
| The composition of the urine microbiome before and after urine transfusion | Percentage of the total microbiome occupied per genus by 16S sequencing | 6 months | 
| Frequency of UTIs after urine transfusions | The number of UTIs during the follow-up period of 6 months after the urine transfusions | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Urine transfusion, Recurrent urinary tract infection, Urinary microbiota