Clinical trial NCT03142295: Controlled Human Urine Transfusion for UTI
Official title: Safety and Tolerability of Controlled Human Urine Transfusion for Urinary Tract Infection Prevention (SHUTUP): a Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Recurrent Urinary Tract Infection
Safety Issues
Keywords: Urine transfusion
Recurrent urinary tract infection
Urinary microbiota
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2017-05-05
Enrollment: 6
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: prospective, open label pilot clinical trial.
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Safety
timeFrame: 6 months
Secondary outcomes:
measure: Diversity of the urine microbiome after urine transfusion
timeFrame: 6 months
measure: The composition of the urine microbiome before and after urine transfusion
timeFrame: 6 months
measure: Frequency of UTIs after urine transfusions
timeFrame: 6 months
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: Zuid-Holland
Study officials:
affiliation: LUMC
name: Imro Vlasveld, MD
role: PRINCIPAL_INVESTIGATOR
References: