Alanyl-glutamine for CDI

• ClinicalTrials.gov Identifier: NCT04305769
• Recruitment Status: Not yet recruiting
• First Posted: March 12, 2020
• Last Update Posted: March 12, 2020
• Sponsor: University of Virginia
• Collaborator: Imperial College London
• Information provided by (Responsible Party): Cirle Warren, MD, University of Virginia

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Clostridioides Difficile Infection; Clostridium Difficile Infection; Clostridium Difficile Diarrhea; Clostridia Difficile Colitis	Drug: Alanyl-glutamine	Phase 2

Study Design

• 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
• Estimated Study Start Date: August 2020
• Estimated Primary Completion Date: August 2024
• Estimated Study Completion Date: November 2024

Arms and Interventions

Arm	Intervention/treatment
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: Alagln; AQ; glutamine
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: Alagln; AQ; glutamine
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: Alagln; AQ; glutamine
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: Alagln; AQ; glutamine

Outcome Measures

Primary Outcome Measures :

1. Recurrent C. difficile infection [ Time Frame: Within 60 days post-treatment ]

Secondary Outcome Measures :

1. Mortality [ Time Frame: Within 60 days post-treatment ]

Eligibility Criteria

• Ages Eligible for Study: 65 Years to 110 Years (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Cirle Warren, MD, Associate Professor, University of Virginia
• ClinicalTrials.gov Identifier: NCT04305769
• Other Study ID Numbers: 200046
• First Posted: March 12, 2020
• Last Update Posted: March 12, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Infection; Communicable Diseases; Clostridium Infections; Diarrhea; Signs and Symptoms, Digestive; Signs and Symptoms; Gram-Positive Bacterial Infections; Bacterial Infections