Using alanyl-glutamine to treat C. difficile infections

Alanyl-glutamine Supplementation of Standard Treatment for C. Difficile Infection: a Randomized, Double-blind, Placebo-controlled Trial

This study is testing if taking alanyl-glutamine can help people with C. difficile infections recover better and prevent the infection from coming back.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 260 (estimated)
• Ages: 18 Years to 105 Years
• Sex: All
• Sponsor: University of Virginia (Academic / other)
• Locations: 2 sites (Charlottesville, Virginia and 1 other locations)
• Trial ID: NCT04305769 on ClinicalTrials.gov

What this trial studies

This Phase II trial investigates the effectiveness and safety of oral alanyl-glutamine supplementation in patients with uncomplicated C. difficile infections. Participants will be randomly assigned to receive either alanyl-glutamine at varying doses or a placebo for ten days, alongside standard treatment with oral vancomycin or fidaxomicin. The study aims to assess the impact of alanyl-glutamine on recurrence and mortality rates, as well as its effects on inflammatory markers and intestinal microbiota. A total of 260 patients will be enrolled and monitored for 60 days post-treatment to evaluate outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older who have been diagnosed with uncomplicated C. difficile infections and are receiving standard therapy.

Not a fit: Patients with severe complications such as hypotension, megacolon, or those in intensive care may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the recurrence and mortality associated with C. difficile infections.

How similar studies have performed: While this approach is novel, similar studies have shown promise in using adjunctive therapies to improve outcomes in C. difficile infections.

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. Male or female, aged 18 years and older.
4. Admitted to UVA hospital, or seen as an outpatient, or seen at Carilion hospital.
5. Presence of diarrhea\*
6. Episode of C. difficile infection, non-severe or severe uncomplicated.
7. Within 120 hours of receiving standard therapy (oral vancomycin or fidaoxmicin).
8. Must be able to provide informed consent in person or electronically, or if not able to have a LAR to provide consent, in person or remotely via virtual or electronic means.

Exclusion Criteria:

1. At enrollment, presence of any of the following:

   1. Hypotension or shock
   2. Megacolon or moderate to severe ileus
   3. Acute abdomen
   4. Admission to intensive care unit
2. Inability to tolerate oral or enteral medication
3. Presence of other known infectious etiology of diarrhea
4. COVID-19 co-infection at the time of CDI diagnosis.
5. Absolute neutrophil count \<500 mcl
6. Within 100 days of hematologic or solid organ transplant

   • Inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis) or other etiology of non-infectious diarrhea. For patients with history of IBD, allow enrollment if disease is well-controlled and stable (not in flare).
7. Enrollment in another investigational drug trial
8. Current use of alternative treatment for CDI (e.g. antibiotics other than vancomycin or fidaxomicin; IVIg; fecal transplant).
9. On probiotics and not willing to discontinue.
10. Cirrhosis or in participants with ALT \> 3X normal
11. End stage renal disease, unless on dialysis(HD or PD) or creatinine clearance or estimated GFR of \<30mL/min even after adequate hydration
12. Life expectancy of \< 6 months.

Where this trial is running

Charlottesville, Virginia and 1 other locations

• UVA Health Systems — Charlottesville, Virginia, United States (Recruiting)
• Carilion Clinic — Roanoke, Virginia, United States (Recruiting)

Conditions Clostridioides Difficile Infection; Clostridium Difficile Infection; Clostridium Difficile Diarrhea; Clostridia Difficile Colitis