Alanyl-glutamine Supplementation for C. Difficile Treatment (ACT) (ACT)

  • STATUS
    Recruiting
  • End date
    Jun 14, 2025
  • participants needed
    260
  • sponsor
    University of Virginia
Updated on 14 June 2022

Summary

This is a randomized, double-blind, placebo-controlled trial to determine the optimal dose and safety of oral alanyl-glutamine between 4, 24, and 44 g doses administered for 10 days with standard therapy among first time incident cases of uncomplicated C. difficile infection (CDI) in hospitalized persons aged 65 or older. Our hypothesis is that alanyl-glutamine supplementation will decrease recurrence and mortality from CDI and these outcomes will be associated with improvement of inflammatory markers and restoration of intestinal microbiota function.

Description

This is a Phase II randomized, placebo-controlled, double-blinded, dose-ranging study to determine optimal effective dose and safety of AQ between 0, 4, 24, and 44 g doses administered orally for ten days concurrent with standard treatment (oral vancomycin at UVa) among first time incident cases of uncomplicated CDI in hospitalized persons age 50 and older. Our hypothesis is that AQ will reduce recurrence (primary outcome) and mortality (secondary outcome) at 60 days post-treatment. Furthermore, the investigators hypothesize that alanyl-glutamine supplementation will be associated with decreased intestinal and systemic inflammation and improvement of intestinal microbial and metabolic profiles. The investigators plan to enroll 260 patients, equally divided into 4 arms. Upon enrollment, participants will be randomized to either receive AQ at 4, 24, or 44 g or placebo (water). Study agent is administered once a day, orally or enterally, if feeding tube is present. Because the investigators are enrolling subjects over a longer period of time, block randomization will be used to ensure that relative temporal balance is maintained throughout the trial. Participants will be followed up daily during treatment for adverse event monitoring and weekly for 60 days post-treatment for recurrences and survival. Blood, urine and stool specimens will be collected at days 0, 10 and 70 to assay for markers of inflammation and microbial and metabolic profiling.

The data set utilized for all initial baseline feature and demographic reporting will be the Intention to Treat Analysis Dataset, which will be comprised of all randomized participants. The primary dataset will be a Modified Intention to Treat Analysis Dataset for all endpoints, comprised of all participants who took at least one dose of study intervention (placebo or treatment), regardless of completeness of follow-up outcome data. The Safety Analysis Dataset will be all participants who took at least one dose of study intervention. The Per Protocol Analysis Dataset will be those patients who took at least 9 doses of study intervention for 9 days of the treatment period (10 days). Analysis will utilize ANOVA unless statistically significant differences in the distribution of baseline characteristics or features of non-normality are detected and relevant, at which point contingency utilization of ANCOVA, logistic regression, or other approaches as appropriate will be implemented. Treatment group level rates will be presented as incidence risk ratios relative to the control (placebo) group with 95% confidence intervals.

Safety endpoints will be evaluated on an individual AE by AE event via the DSMB and utilizing summary statistics during treatment and through duration of follow up. Adverse events will be presented by System Organ Class and will include information on start and stop date, severity, projected relationship, expectedness, and outcome and duration (the latter two after the event is considered to have concluded).

Details
Condition Clostridioides Difficile Infection, Clostridium Difficile Infection, Clostridium Difficile Diarrhea, Clostridia Difficile Colitis
Treatment Alanyl-glutamine
Clinical Study IdentifierNCT04305769
SponsorUniversity of Virginia
Last Modified on14 June 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, aged 18 years and older
Admitted in the hospital
Presence of diarrhea
Stool positive for C. difficile tcdB
1st episode of C. difficile infection, non-severe or severe uncomplicated
If with previous episodes of C. difficile infection, last episode must be at least 1 year ago; OR patient received fecal transplant (for recurrent CDI) more than 2 months prior to enrollment
Within 96 hours of receiving standard therapy (oral vancomycin at UVA)
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

At enrollment, presence of any of the following
Hypotension or shock
Megacolon or moderate to severe ileus
Acute abdomen
Admission to intensive care unit
Inability to tolerate oral or enteral medication
Presence of other known infectious etiology of diarrhea
Inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis) or other etiology of non-infectious diarrhea
Enrollment in another investigational drug trial
Current use of alternative treatment for CDI (e.g. antibiotics other than vancomycin or fidaxomicin; IVIg; fecal transplant)
On probiotics and not willing to discontinue
Cirrhosis or in participants with ALT > 3X normal
End stage renal disease, on dialysis, or creatinine clearance or estimated GFR of <30mL/min even after adequate hydration
Life expectancy of < 6 months
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