Phase 1/ 2 Trial of Phage Therapy for Recurrent UTIs in Kidney Transplant Recipients
University of California, San Diego
Summary
This proposal will take an important first step in the study of phage therapy for treatment of recurrent urinary tract infection (rUTI) in female kidney transplant recipients (KTR); a common condition that is associated with increasing multidrug resistance, sickness, loss of kidney function and death. The investigators will conduct a randomized phase I/II pilot clinical trial of targeted phage therapy versus placebo in asymptomatic female KTR with a history of rUTI due to Escherichia coli to assess safety, tolerability, and feasibility of this approach, possible efficacy, and changes in the gut and urinary microbiome during the 180 days of the study. This highly innovative and impactful proposal will provide proof of concept data and also inform the design of a subsequent larger phase III clinical trial of phage therapy for rUTI treatment in KTR and will have broad downstream effects within the fields of infectious diseases and transplantation.
Description
The overarching hypothesis is that phage therapy directed against E. coli in female KTR is safe and associated with a reduction in UTI event rate via a targeted impact on the gut and urinary microbiome. This is a Phase 1/ 2 randomized, placebo-controlled clinical trial. * A description of methods to be used to minimize bias Participants will be randomized to one of 2 arms - one active intervention phage therapy and the second is active intervention control arm (normal saline placebo). Participants will not be aware of study assignment and the medication delivered to them will look identical -…
Eligibility
- Age range
- 18+ years
- Sex
- Female
- Healthy volunteers
- No
Inclusion Criteria: 1. Female kidney transplant recipients, aged 18 and older with a confirmed diagnosis of a history of recurring UTI with E. coli as their typical uropathogen. 2. Two urine culture proven UTIs in prior 6 months or three in prior 12 months due to E coli. UTI is defined as any change in symptoms from baseline urinary comfort (dysuria, hematuria, abdominal/flank pain, increased urinary frequency) or systemic signs of infection (fever, chills, systemic inflammatory reaction syndrome etc.) associated with a positive urine culture with bacterial growth of ≥104 colony forming units…
Interventions
- Drugphage therapy
phage therapy will consist of a combination of three lytic phages that are active against the participant's E. coli isolates and will be administered intravenously twice daily for 7 days.
- Drugcontrol
Participants assigned to the control arm will start a 7-day course of intravenous sterile normal saline (placebo) administered twice daily.
Location
- University of California, San DiegoLa Jolla, California