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

NCT04305769 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 200046
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 2

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, or outpatient, persons aged 18 or older. The investigators 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Number of participants with recurrent CDI.

  Documented C difficile infection defined by presence of recurrent diarrhea with stool positive for C difficile assay necessitating treatment with anti-C. difficile antibiotic.

  Within 60 days post-treatment

Secondary Outcomes (1)

• Number of participants who died post-study treatment

  Until 60 days post-treatment

Study Arms (4)

Alanyl-glutamine 0g

PLACEBO COMPARATOR

Drug: Alanyl-glutamine

Alanyl-glutamine 4g

EXPERIMENTAL

Drug: Alanyl-glutamine

Alanyl-glutamine 24g

EXPERIMENTAL

Drug: Alanyl-glutamine

Alanyl-glutamine 44g

EXPERIMENTAL

Drug: Alanyl-glutamine

Interventions

Alanyl-glutamine DRUG

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.

Also known as: Alagln, AQ, glutamine

Alanyl-glutamine 0g; Alanyl-glutamine 24g; Alanyl-glutamine 44g; Alanyl-glutamine 4g

Eligibility Criteria

• Age: 18 Years - 105 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 to UVA hospital, or seen as an outpatient, or seen at Carilion hospital.
• Presence of diarrhea\*
• Episode of C. difficile infection, non-severe or severe uncomplicated.
• Within 120 hours of receiving standard therapy (oral vancomycin or fidaoxmicin).
• 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.

You may not qualify if:

• 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
• COVID-19 co-infection at the time of CDI diagnosis.
• Absolute neutrophil count \<500 mcl
• 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).
• 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

Sponsors & Collaborators

• University of Virginia: lead
• Carilion Clinic: collaborator
• University of Southampton: collaborator

Study Sites (2)

UVA Health Systems

Charlottesville, Virginia, 22903, United States

RECRUITING

Carilion Clinic

Roanoke, Virginia, 24014, United States

RECRUITING

Related Publications (1)

• Warren CA, Shin JH, Bansal EN, Costa DVDS, Wang XQ, Wu M, Swann JR, Behm BW, Targonski PV, Archbald-Pannone L. Alanyl-glutamine supplementation for Clostridioides difficile infection treatment (ACT): a double-blind randomised controlled trial study protocol. BMJ Open. 2023 Jul 19;13(7):e075721. doi: 10.1136/bmjopen-2023-075721.

  PMID: 37474181 DERIVED

MeSH Terms

Conditions

Clostridium Infections; Enterocolitis, Pseudomembranous

Interventions

alanylglutamine; Glutamine

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Neutral

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Professor

Model Details: 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.

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 12, 2020
• Study Start: June 1, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: October 26, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 6 months after publication
• Access Criteria: To be determined later.

Locations

US (2)