Phage Therapy for Urinary Tract Infections in Spinal Cord Injury

(Phage Trial)

Overseen By Barbara W Trautner, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Barbara Wells Trautner

Must not be taking: Urine acidifiers

Disqualifiers: Neutropenia, Organ transplant, HIV, others

Trial Summary

What is the purpose of 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.

Will I have to stop taking my current medications?

The trial protocol does not clearly specify if you need to stop taking your current medications. However, it mentions that prescription drugs, over-the-counter medications, and supplements that acidify the urine are excluded unless deemed acceptable by the sponsor-investigator.

What data supports the effectiveness of the treatment Phage Therapy for Urinary Tract Infections in Spinal Cord Injury?

Research shows that phage therapy has been effective in treating urinary tract infections caused by drug-resistant bacteria in both animal studies and human cases. In one study, phage therapy cured urinary tract infections in rats, and another study found it to be 84% effective in treating urinary infections in humans. ^{1 2 3 4 5}

Is phage therapy generally safe for humans?

Phage therapy has been used successfully in some cases as an alternative treatment for infections, and studies in animals suggest it can be safe, but more research is needed to confirm its safety in humans. ^{1 2 6 7 8}

How is phage therapy different from other treatments for urinary tract infections?

Phage therapy is unique because it uses viruses called bacteriophages to specifically target and kill bacteria causing the infection, unlike antibiotics which can affect a broad range of bacteria and lead to resistance. This treatment is particularly promising for infections that are resistant to multiple drugs and can be administered locally or orally, offering a targeted approach with potentially fewer side effects. ^{1 2 3 4 9}

Research Team

Barbara W Trautner, MD, PhD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for adults over 18 with spinal cord injury (SCI) who have neurogenic bladders and E. coli bacteriuria, using catheters for bladder drainage. Participants must consent to study procedures, use two forms of contraception if applicable, and be available for the study duration. Those hospitalized or able to visit the clinic for treatment initiation can join.

Inclusion Criteria

I am over 18 and have a neurogenic bladder due to a spinal cord injury.

I have a urinary infection with E. coli at a specific level.

I use a catheter regularly for urination.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 30 days

Treatment

Participants receive investigational phage therapy or placebo intravesicularly twice a day for 7 days

7 days

14 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with assessments on Days 14, 21, and 35

35 days

3 visits (in-person)

Treatment Details

Interventions

• Phage Therapy (Virus Therapy)

Trial Overview The trial tests a new phage therapy against a placebo in SCI patients with bladder colonization by E. coli. It's designed to check safety and how the body processes the therapy (pharmacokinetics) and responds to it (pharmacodynamics), in a controlled environment where participants are randomly assigned.

Participant Groups

Group I: Phage Arm Experimental Treatment 1 Intervention

A sterile solution of one to three individual phages (cocktail) (3 x 10\^8 plaque forming units \[PFU\]) phage(s) will be administered intravesicularly (instilled into the participant's bladder via catheter) twice a day for 7 days. The name of the active treatment IP is TAILФR Phage Cocktail (TPC).

Group II: Placebo Arm Placebo Group 1 Intervention

Sterile 0.9% saline solution will be instilled into the bladder via catheter twice a day for 7 days

Who Is Running the Clinical Trial?

Barbara Wells Trautner

Lead Sponsor

Trials

1

Recruited

30+

Findings from Research

Phage therapy has shown promise as an alternative treatment for multidrug-resistant infections, with some successful case studies already reported.

This commentary highlights the potential of phage therapy specifically for treating urinary tract infections, suggesting it could be a valuable tool in addressing antibiotic resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phage therapy for urinary tract infections: does it really work? González-Villalobos, E., Molina-López, J., Balcázar, JL.[2022]

Bacteriophage therapy was effective in curing urinary tract infections (UTIs) in rats when administered at higher concentrations (1×10^8 PFU/ml and 1×10^7 PFU/ml).

The lowest concentration (1×10^6 PFU/ml) required more frequent doses to effectively eliminate the bacteria, suggesting that optimizing dosage and frequency is crucial for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacteriophage therapy for Escherichia coli-induced urinary tract infection in rats. Bhargava, K., Nath, G., Dhameja, N., et al.[2023]

Bacteriophage therapy showed a high clinical efficacy of 92% and bacteriological efficacy of 84% in treating urinary infections in 46 patients, indicating it is a promising alternative to traditional antibacterial treatments.

Phagotherapy was found to be effective and safe, especially when used alone or in combination with antibiotics, suggesting it could help reduce the issues of antibiotic resistance and dysbacteriosis associated with conventional antibacterial therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy of bacteriophage preparations in treating inflammatory urologic diseases]. Perepanova, TS., Darbeeva, OS., Kotliarova, GA., et al.[2020]

The study successfully isolated and characterized two bacteriophages that effectively target local uropathogenic E. coli strains responsible for urinary tract infections, showing promise for phage therapy as a treatment option.

These phages, when combined into a cocktail, demonstrated strong activity against specific E. coli phylogroups (B2 and D), indicating their potential for tailored therapeutic applications in combating antibiotic-resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of Anti-Bacterial Effect of the Two New Phages against Uropathogenic Escherichia coli. Slobodníková, L., Markusková, B., Kajsík, M., et al.[2021]

Phage therapy using HP3 and ES17 against uropathogenic E. coli (UPEC) showed that while resistance can develop quickly in the urinary environment, this resistance comes with fitness costs that may make the bacteria more vulnerable to host immunity and antibiotics.

Phage-resistant UPEC strains exhibited reduced growth in human urine and were less effective at colonizing the bladder in a mouse model, suggesting that phage therapy could be a viable treatment option for UTIs if resistance leads to decreased bacterial fitness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phage Resistance Accompanies Reduced Fitness of Uropathogenic Escherichia coli in the Urinary Environment. Zulk, JJ., Clark, JR., Ottinger, S., et al.[2022]

In a study of 136 patients with spinal cord injury, oral immunomodulation therapy using E. coli fractions significantly reduced the frequency of recurrent urinary tract infections (UTIs) from 93.4% to 59.6% over 12 months.

The therapy also increased the proportion of patients reporting no UTIs from 2.2% to 20.6%, indicating its potential as an effective preventive treatment for UTIs in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of oral immunomodulation therapy on urinary tract infections in individuals with chronic spinal cord injury-A retrospective cohort study. Krebs, J., Fleischli, S., Stoyanov, J., et al.[2020]

In a study involving 21 spinal cord injured patients, the use of E. coli 83972 for bladder colonization was found to be safe, with successful long-term colonization achieved in 13 participants for an average of 12.3 months without any urinary tract infections (UTIs) during that time.

Patients who were successfully colonized reported a significant reduction in the frequency of symptomatic UTIs, going from an average of 3.1 infections per year before colonization to none while colonized, suggesting that E. coli 83972 could be an effective preventive strategy for UTIs in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary tract infection prophylaxis using Escherichia coli 83972 in spinal cord injured patients. Hull, R., Rudy, D., Donovan, W., et al.[2007]

In a study involving 90 female albino mice, a phage cocktail was found to effectively clear uropathogenic E. coli from the urinary tract, demonstrating its potential as a treatment for urinary tract infections (UTIs).

The phage cocktail's success is attributed to its broader host range compared to a single phage, which showed no therapeutic effect, highlighting the importance of using a combination of phages for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Phage Cocktail Therapy of the Urinary Tract Infection in a Mouse Model. Mijbel Ali, B., Gatea Kaabi, SA., Al-Bayati, MA., et al.[2023]

A newly developed phage cocktail effectively targets and lyses over 80% of contemporary E. coli strains associated with catheter-associated urinary tract infections (CAUTI), demonstrating strong efficacy against both young and mature biofilms.

Combining this phage cocktail with antibiotics not only enhances treatment effectiveness but also helps prevent the development of phage-resistant E. coli, suggesting a promising therapeutic strategy for managing CAUTI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Phage Cocktails to Treat E. coli Catheter-Associated Urinary Tract Infection and Associated Biofilms. Sanchez, BC., Heckmann, ER., Green, SI., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Phage therapy for urinary tract infections: does it really work? [2022]

2. England pubmed.ncbi.nlm.nih.gov

Bacteriophage therapy for Escherichia coli-induced urinary tract infection in rats. [2023]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The efficacy of bacteriophage preparations in treating inflammatory urologic diseases]. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Characterization of Anti-Bacterial Effect of the Two New Phages against Uropathogenic Escherichia coli. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Phage Resistance Accompanies Reduced Fitness of Uropathogenic Escherichia coli in the Urinary Environment. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Effects of oral immunomodulation therapy on urinary tract infections in individuals with chronic spinal cord injury-A retrospective cohort study. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Urinary tract infection prophylaxis using Escherichia coli 83972 in spinal cord injured patients. [2007]

8. Iran pubmed.ncbi.nlm.nih.gov

A Novel Phage Cocktail Therapy of the Urinary Tract Infection in a Mouse Model. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Development of Phage Cocktails to Treat E. coli Catheter-Associated Urinary Tract Infection and Associated Biofilms. [2023]