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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 65 Years and Over
Gender All
More Inclusion & Exclusion 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 > 65 years. 4. Admitted in the hospital. 5. Presence of diarrhea* 6. Stool positive for C. difficile tcdB and TcdB. 7. 1st episode of C. difficile infection, non-severe or severe uncomplicated. 8. Within 48 hours of receiving standard therapy (oral vancomycin at UVA)

Exclusion Criteria:

1. At enrollment, presence of any of the following:
  • - Hypotension or shock.
  • - Megacolon or moderate to severe ileus.
  • - Acute abdomen.
  • - Admission to intensive care unit.
2. Inability to tolerate oral or enteral medication. 3. Presence of other known infectious etiology of diarrhea. 4. Inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis) or other etiology of non-infectious diarrhea. 5. Enrollment in another investigational drug trial. 6. Current use of alternative treatment for CDI (e.g. antibiotics other than vancomycin or fidaxomicin; IVIg; fecal transplant). 7. On probiotics and not willing to discontinue. 8. Cirrhosis or in participants with ALT > 3X normal. 9. End stage renal disease, on dialysis, or creatinine clearance or estimated GFR of <30mL/min even after adequate hydration. 10. Life expectancy of < 6 months.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04305769
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Virginia
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherOther
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Clostridioides Difficile Infection, Clostridium Difficile Infection, Clostridium Difficile Diarrhea, Clostridia Difficile Colitis
Additional Details

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).

Arms & Interventions

Arms

Placebo Comparator: Alanyl-glutamine 0g

Experimental: Alanyl-glutamine 4g

Experimental: Alanyl-glutamine 24g

Experimental: Alanyl-glutamine 44g

Interventions

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.

Contact a Trial Team

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UVA Health Systems, Charlottesville, Virginia

Status

Recruiting

Address

UVA Health Systems

Charlottesville, Virginia, 22903

Site Contact

Cirle Warren, M.D.

CA6T@hscmail.mcc.virginia.edu

434-270-1082

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