Using phage therapy to treat bladder infections in spinal cord injury patients

A Phase 1B Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Bacteriophage Therapy in Spinal Cord Injury Patients With Bacteriuria

This study is testing if a new treatment using viruses to target bacteria can help people with spinal cord injuries who have bladder infections caused by E. coli.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Washington University School of Medicine (Academic / other)
• Locations: 2 sites (St Louis, Missouri and 1 other locations)
• Trial ID: NCT06559618 on ClinicalTrials.gov

What this trial studies

This Phase 1b study evaluates the safety and tolerability of personalized bacteriophage therapy in adults with spinal cord injuries who have asymptomatic bacteriuria caused by E. coli. Participants will be randomly assigned to receive either the phage therapy or a placebo, administered directly into the bladder via catheter for seven days. The study aims to assess the pharmacokinetics and pharmacodynamics of the treatment, with follow-up assessments conducted over a 35-day period post-treatment. Approximately 30 participants will be enrolled, focusing on those with neurogenic bladders requiring catheterization.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with spinal cord injuries, neurogenic bladders, and confirmed E. coli bacteriuria requiring catheterization.

Not a fit: Patients who are unable to provide informed consent or have received new antibiotics shortly before the study may not benefit from this therapy.

Why it matters

Potential benefit: If successful, this therapy could provide a novel and effective treatment option for bladder infections in spinal cord injury patients, potentially reducing reliance on antibiotics.

How similar studies have performed: While phage therapy is a novel approach in this specific context, similar studies have shown promise in treating bacterial infections with phage therapy.

Eligibility criteria

Inclusion Criteria:

1. Provision of signed and dated informed consent form.
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. 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).
4. ASB with E. coli present in a quantity of ≥ 104 CFU/mL.
5. Require an indwelling (transurethral or suprapubic) or intermittent catheterization for bladder drainage.
6. Women of childbearing potential and men with female partners of childbearing potential must use two forms of effective contraception during the study and for two weeks afterwards.
7. Participant will be hospitalized during the 7 days of treatment or will be willing to attend clinic visits either (a) daily for the 7 days of treatment, or (b) on Day 1 and Day 7 of dosing. On Day 1, the participant will receive in-person training on instillation of the IP into the bladder.

Exclusion Criteria:

1. Unable to provide informed consent for themselves.
2. Received a new antibiotic expected to kill the Gram-negative organisms in the urine between initial enrollment urine culture and the time of randomization.
3. History of neutropenia, defined by ANC \< 1000 per µL within 6 months prior to screening.
4. History of organ transplantation.
5. Presence of a surgically modified bladder, except for a repaired ruptured bladder.
6. HIV with a CD4 count \< 200 cells per µL.
7. Unstable vital signs (e.g., fever, hypotension)
8. Symptoms of active urinary tract infection defined as fever, autonomic dysreflexia, generalized increase in spasticity, bladder spasms, new sweating, increase or change in lower abdominal pain, increase in burning or pain when passing urine, increase in burning or pain during catheterization, blood in the urine, or an increased sensation of urinary urgency (MedStar Health, Urinary Symptom Questionnaires for Neurogenic Bladder \[USQNB\]). The presence of any one of these symptoms, unless explained by a non-urinary or non-infectious condition, will be an exclusion criterion.
9. Known urinary obstruction.
10. Medical devices in the urinary tract (other than urinary catheters)
11. Unless deemed acceptable by the sponsor-investigator, prescription drugs, OTC medications and supplements that acidify the urine are excluded.
12. Stage 4 or greater chronic kidney disease
13. Pregnant or breastfeeding female
14. Three or more episodes of autonomic dysreflexia in prior 30 days; defined as those patients who have a SCI and who have had a documented sudden increase in systolic blood pressure of greater than 40 mmHg due to an irritation or stimulation (including bladder or bowel irritation) below the level of the SCI. Autonomic dysreflexia can include findings of hypertensive crisis or emergency, clinically significant bradycardia/tachycardia, severe headache or other severe reaction requiring an acute intervention. The sponsor-investigator will evaluate if a history of severe autonomic dysreflexia is suspected but not clearly identified.
15. In the opinion of the sponsor-investigator, medical or psychiatric illness that would interfere with participation such as active, severe, progressive, or uncontrolled hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, or neurologic disease.

Where this trial is running

St Louis, Missouri and 1 other locations

• Washington University in St Louis — St Louis, Missouri, United States (Recruiting)
• Michael E. DeBakey VA Medical Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Barbara W Trautner, MD, PhD — Washington University School of Medicine
• Study coordinator: Barbara W Trautner, MD, PhD

Conditions Bacteriuria; Spinal Cord Injuries; Asymptomatic Bacteriuria; Escherichia Coli; Bacteriophage; Phage Therapy; Spinal Cord Injury; Intravesicular infusion