Alanyl-glutamine Supplementation for C. Difficile Treatment (ACT) (ACT)
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ClinicalTrials.gov Identifier: NCT04305769 |
Recruitment Status :
Recruiting
First Posted : March 12, 2020
Last Update Posted : June 9, 2022
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Condition or disease | Intervention/treatment | Phase |
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Clostridioides Difficile Infection Clostridium Difficile Infection Clostridium Difficile Diarrhea Clostridia Difficile Colitis | Drug: Alanyl-glutamine | Phase 2 |
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).
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 260 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | Block randomization will be applied to assign participants to one of the four study groups, either one of the three experimental (AQ) or control (placebo) group in 1:1:1:1 allocation from a list containing the randomized and blinded treatment assignments. |
Masking: | Triple (Participant, Care Provider, Investigator) |
Primary Purpose: | Treatment |
Official Title: | Alanyl-glutamine Supplementation of Standard Treatment for C. Difficile Infection: A Randomized, Double-blind, Placebo-controlled Trial |
Actual Study Start Date : | June 1, 2021 |
Estimated Primary Completion Date : | December 2024 |
Estimated Study Completion Date : | June 2025 |

Arm | Intervention/treatment |
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Placebo Comparator: Alanyl-glutamine 0g |
Drug: Alanyl-glutamine
The study agent is AQ, a dipeptide with a glutamine amino group joined to an alanyl residue. It has the following chemical structure: C8H15N3O4. It is a non-animal product available in the form of white crystals or crystalline powder. It is odorless, tasteless, stable and highly soluble.
Other Names:
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Experimental: Alanyl-glutamine 4g |
Drug: Alanyl-glutamine
The study agent is AQ, a dipeptide with a glutamine amino group joined to an alanyl residue. It has the following chemical structure: C8H15N3O4. It is a non-animal product available in the form of white crystals or crystalline powder. It is odorless, tasteless, stable and highly soluble.
Other Names:
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Experimental: Alanyl-glutamine 24g |
Drug: Alanyl-glutamine
The study agent is AQ, a dipeptide with a glutamine amino group joined to an alanyl residue. It has the following chemical structure: C8H15N3O4. It is a non-animal product available in the form of white crystals or crystalline powder. It is odorless, tasteless, stable and highly soluble.
Other Names:
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Experimental: Alanyl-glutamine 44g |
Drug: Alanyl-glutamine
The study agent is AQ, a dipeptide with a glutamine amino group joined to an alanyl residue. It has the following chemical structure: C8H15N3O4. It is a non-animal product available in the form of white crystals or crystalline powder. It is odorless, tasteless, stable and highly soluble.
Other Names:
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- Number of participants with recurrent CDI. [ Time Frame: Within 60 days post-treatment ]Documented C difficile infection defined by presence of recurrent diarrhea with stool positive for C difficile assay necessitating treatment with anti-C. difficile antibiotic.
- Number of participants who died post-study treatment [ Time Frame: Until 60 days post-treatment ]Documentation of death from any cause occurring during study treatment and 60 days after study treatment

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Ages Eligible for Study: | 18 Years to 105 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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:
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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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04305769
United States, Virginia | |
UVA Health Systems | Recruiting |
Charlottesville, Virginia, United States, 22903 | |
Contact: Cirle Warren, M.D. 434-270-1082 CA6T@hscmail.mcc.virginia.edu | |
Contact: MaryJane Strickland, B.S.,M.ed 4347601267 mjs7w@virginia.edu | |
Principal Investigator: Cirle Warren, M.D. |
Responsible Party: | Cirle Warren, MD, Associate Professor, University of Virginia |
ClinicalTrials.gov Identifier: | NCT04305769 |
Other Study ID Numbers: |
200046 |
First Posted: | March 12, 2020 Key Record Dates |
Last Update Posted: | June 9, 2022 |
Last Verified: | June 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | All IPD that underlie results in publication |
Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) |
Time Frame: | 6 months after publication |
Access Criteria: | To be determined later. |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Infections Communicable Diseases Clostridium Infections Diarrhea Disease Attributes |
Pathologic Processes Signs and Symptoms, Digestive Gram-Positive Bacterial Infections Bacterial Infections Bacterial Infections and Mycoses |