Bacteriophage Therapy in Spinal Cord Injury Patients With Bacteriuria

ConditionsBacteriuria Spinal Cord Injuries Asymptomatic Bacteriuria Escherichia Coli

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18+

SponsorBarbara Trautner

About this trial

This is a Phase 1b study to assess the safety, tolerability, PK, and PD of investigational phage therapy (IP) in adults with SCI and bladder colonization (ASB). It is a single-center, randomized, double-blind, placebo-controlled study in adults with SCI with neurogenic bladders and bacteriuria who use indwelling catheters, or who require intermittent catheterization for bladder drainage.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Provision of signed and dated informed consent form.

Stated willingness to comply with all study procedures and availability for the duration of the study.

Adult (> age 18) with a diagnosis of Spinal Cord Injury/Disease (SCI/D) and neurogenic bladder. Eligible participants may include inpatients in the SCI care unit or outpatients receiving care at participating sites, regardless of the underlying cause of SCI (e.g., trauma, tumors or demyelinating).

ASB with E. coli present in a quantity of ≥ 104 CFU/mL.

Disqualifiers

Unable to provide informed consent for themselves.

Received a new antibiotic expected to kill the Gram-negative organisms in the urine between initial enrollment urine culture and the time of randomization.

History of neutropenia, defined by ANC < 1000 per µL within 6 months prior to screening.

History of organ transplantation.

Trial design

Design model

Parallel

Treatments tested in this trial

Phage Therapy
Drug
A 20 mL sterile solution containing one to three individual phage drug substances (TPC) with total strength (potency) 3 x 10\^8 plaque-forming units (PFU), will be administered intravesicularly twice a day (one instillation in the morning and one in the evening \[at least six hours apart\], respectively) for 7 days. The selection of individual phages to include in the TPC are personalized/customized for each participant per phage susceptibility testing to the participant's urinary E. coli (testing is conducted by TAILФR Service Center). Each dose of TPC will be followed with a 10 mL flush of sterile 0.9% saline solution.
Placebo
Other intervention
Sterile 0.9% saline solution also 20 mL, followed with a 10 mL flush of the same solution.

Treatment groups

30 Participants

are divided into 2 treatment groups

Group A: Phage ArmExperimental treatment 1 intervention

Group B: Placebo ArmPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

To evaluate the safety and tolerability of phage therapy in adults ≥18 years of age with spinal cord injury (SCI) and bacteriuria with Escherichia coli (E. coli)

Safety and tolerability analysis of Adverse Events. The urinary symptom questionnaires provided by MedStar Health, USQNB will be used as a daily study diary. Participant's charts for AEs while they are hospitalized, and during study visits on days 14, 21, and 35 if they have been discharged before Day 14. Blood samples will be collected for chemistry and hematology on days 1, 3, 7, 14, 21, and 35. Urine samples will be collected to detect and analyze markers of inflammation on Days 1, 2, 3, 5, 7, 14, 21, and 35.

Time frame

2 years

Secondary outcomes

To evaluate the pharmacokinetics (PK) of investigational phage therapy

Blood samples will be collected to quantify phage titers, which will be measured as PFU (plaque-forming units) per mL (milliliter) of blood. To quantify phage titers, we will perform PCR to measure copies/volume of phage titer compared to a standard control of purified phage.

Time frame

2 years

To evaluate of the pharmacodynamics (PD) of investigational phage therapy

Urine samples will be collected to analyze 1 log reduction in the urinary E. coli on Days 1, 2, 3, 5, 7, 14, 21, and 35. Analysis of recurrence of urinary E. coli colonization, incidence of urinary tract infection based on clinical signs and symptoms. Microbiological cure, defined as \<10\^3 CFU/mL of E. coli in the urine on Day 7.

Time frame

2 years

Other outcomes

To explore the influence of phage therapy on the urinary tract microbiota

Urine samples will be collected to analyze microbiome diversity, comparing pre-treatment sample to end of study sample. Emergence of phage resistance among the targeted E. coli in the bladder.

Time frame

2 years

To explore the influence of phage therapy on the digestive tract microbiota

Analysis of stool sample microbiome diversity, comparing pre-treatment to end of study.

Time frame

2 years