Alanyl-glutamine for Clostridium Difficile Infection

(ACT Trial)

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Virginia

Must be taking: Vancomycin, Fidaxomicin

Must not be taking: Probiotics, Other antibiotics

Disqualifiers: COVID-19, IBD flare, Cirrhosis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 10 days

260 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests alanyl-glutamine, a supplement, to determine if it reduces the recurrence and mortality of Clostridium difficile infections (CDI). Researchers compare different doses of alanyl-glutamine to identify the safest and most effective dose alongside standard treatments. They aim to improve gut health and reduce inflammation. Individuals who have recently begun standard treatment, such as oral vancomycin or fidaxomicin, for a non-severe or uncomplicated CDI episode and have diarrhea may be suitable for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on alternative treatments for C. difficile infection or probiotics unless you are willing to stop them.

Is there any evidence suggesting that alanyl-glutamine is likely to be safe for humans?

Research has shown that alanyl-glutamine is being explored as a potential treatment for Clostridium difficile infections (CDI). It may aid in repairing the gut's natural defenses and reducing inflammation.

Previous patients have demonstrated that alanyl-glutamine is generally well-tolerated. In other studies, when combined with standard treatment, it did not cause major side effects. Some studies are ongoing to determine the optimal doses and ensure safety.

The current trial is in an early stage, so researchers are still gathering safety information. However, since alanyl-glutamine is already under study for other uses, there is some confidence in its safety for humans. Everyone can react differently, so discussing participation with a healthcare provider is important before joining any trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for C. difficile infection?

Researchers are excited about alanyl-glutamine as a treatment for Clostridium difficile infection because it offers a unique approach compared to current antibiotics like vancomycin and metronidazole. Alanyl-glutamine is an amino acid supplement that could potentially strengthen the gut lining and improve intestinal health, thereby reducing infection severity and recurrence. Unlike traditional treatments that directly target the bacteria, alanyl-glutamine works by enhancing the body's natural defenses, offering a novel mechanism of action. This approach could lead to fewer side effects and a lower risk of antibiotic resistance, making it a promising alternative in the fight against this challenging infection.

What evidence suggests that alanyl-glutamine might be an effective treatment for C. difficile infection?

Research has shown that alanyl-glutamine might help treat Clostridium difficile infection (CDI) by healing the gut lining and reducing swelling. Studies indicate that alanyl-glutamine is stable, easily absorbed, and aids in sodium transport, which is important for gut health. This trial will evaluate different dosages of alanyl-glutamine—4g, 24g, and 44g—to determine its effectiveness in lowering the risk of the infection returning and reducing deaths from CDI. Overall, evidence suggests that alanyl-glutamine offers a new way to support gut health and combat this challenging infection. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18 or older with a first-time, uncomplicated C. difficile infection who are within 96 hours of receiving standard therapy and can consent to the study. It's not for those with severe conditions like shock, megacolon, acute abdomen, ICU patients, intolerance to oral medication, other diarrhea causes or on conflicting treatments.

Inclusion Criteria

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

I am currently experiencing diarrhea.

Provision of signed and dated informed consent form

Exclusion Criteria

I had a bone marrow or organ transplant within the last 100 days.

My inflammatory bowel disease is under control and not currently flaring.

I am taking probiotics and do not want to stop.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral alanyl-glutamine or placebo for 10 days concurrent with standard treatment

10 days

Daily visits (in-person or virtual)

Follow-up

Participants are monitored for recurrence and survival, with specimen collection for inflammation and microbial profiling

60 days

Weekly visits (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Alanyl-glutamine

Trial Overview The ACT trial tests different doses (4g, 24g, and 44g) of alanyl-glutamine given orally for ten days alongside standard therapy to see if it reduces recurrence and mortality from C. difficile infections while improving inflammatory markers and gut microbiota function.

How Is the Trial Designed?

Group I: Alanyl-glutamine 4g Experimental Treatment 1 Intervention

Group II: Alanyl-glutamine 44g Experimental Treatment 1 Intervention

Group III: Alanyl-glutamine 24g Experimental Treatment 1 Intervention

Group IV: Alanyl-glutamine 0g Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Carilion Clinic

Collaborator

Trials

85

Recruited

15,400+

University of Southampton

Collaborator

Trials

232

Recruited

2,469,000+

Imperial College London

Collaborator

Trials

1,052

Recruited

15,030,000+

Published Research Related to This Trial

C. difficile can survive in the presence of host antimicrobial proteins like lysozyme due to the Dlt pathway, which enhances its resistance by modifying its cell wall.

The study identified that the σ(V) sigma factor is crucial for regulating the Dlt pathway in response to lysozyme, and both Dlt and σ(V) mutants showed increased virulence in a hamster infection model, highlighting their roles in C. difficile's ability to cause disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clostridium difficile Dlt Pathway Is Controlled by the Extracytoplasmic Function Sigma Factor σV in Response to Lysozyme. Woods, EC., Nawrocki, KL., Suárez, JM., et al.[2020]

Clostridium difficile infections, particularly antibiotic-associated colitis, are increasingly dangerous due to the emergence of more virulent strains, highlighting the need for effective treatments beyond traditional antibiotics like vancomycin and metronidazole.

New therapeutic strategies, including polymer-based toxin-binding agents and monoclonal antibodies targeting the toxins produced by C. difficile, show promise as non-antibiotic options that could effectively manage this toxin-mediated disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxin-binding treatment for Clostridium difficile: a review including reports of studies with tolevamer. Weiss, K.[2020]

A new class of biaryl peptidomimetics was developed, showing potent antibacterial activity against Clostridioides difficile and methicillin-resistant Staphylococcus aureus, with the monocationic compound demonstrating an MIC of 8 μg/mL against C. difficile.

In in vivo studies using a murine model, compounds 28 and 67 significantly reduced the severity and slowed the onset of C. difficile infection, indicating their potential as effective treatments for this serious gastrointestinal infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cationic biaryl 1,2,3-triazolyl peptidomimetic amphiphiles targeting Clostridioides (Clostridium) difficile: Synthesis, antibacterial evaluation and an in vivo C. difficile infection model. Tague, AJ., Putsathit, P., Hutton, ML., et al.[2020]

Peptides derived from a specific region of the TcdB toxin in Clostridium difficile can protect cells from its harmful effects by destabilizing the toxin's structure and preventing it from binding to cells.

One particular peptide, PepB2, forms a complex that alters TcdB's conformation, suggesting a novel approach to developing treatments for Clostridium difficile infections by targeting this critical virulence factor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrinsic Toxin-Derived Peptides Destabilize and Inactivate Clostridium difficile TcdB. Larabee, JL., Bland, SJ., Hunt, JJ., et al.[2020]

Aryl-alkyl-lysines, particularly the compound NCK-10, show promising antimicrobial activity against Clostridium difficile, with effectiveness comparable to the antibiotic vancomycin, and in some cases, even superior to it in vitro.

NCK-10 demonstrated limited permeation across the intestinal tract, suggesting it may be a targeted treatment option for CDI that minimizes systemic exposure, warranting further research into its potential as a novel therapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aryl-alkyl-lysines: Novel agents for treatment of C. difficile infection. Ghosh, C., AbdelKhalek, A., Mohammad, H., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10357635/

Alanyl-glutamine supplementation for Clostridioides ... Alanyl-glutamine (AQ) may be beneficial in treating CDI by its effect on restoring intestinal integrity in the epithelial barrier, ameliorating inflammation ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04305769

Alanyl-glutamine Supplementation for C. Difficile Treatment ... The investigators hypothesis is that alanyl-glutamine supplementation will decrease recurrence and mortality from CDI and these outcomes will be associated with ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3591182/

Glutamine and Alanyl-Glutamine Increase RhoA ... It has been demonstrated that alanyl-glutamine (Ala-Gln) is stable, highly soluble, well tolerated, and at least as effective in driving sodium cotransport and ...

4. withpower.com withpower.com/trial/phase-3-infections-2021-39e21

Alanyl-glutamine for Clostridium Difficile Infection (ACT Trial) Alanyl-glutamine is unique because it is a dipeptide that may help in gut health and repair, potentially offering a novel approach to treating Clostridium ...

5. carilionclinic.org carilionclinic.org/research/infectiousdiseases/cdiff

ALANYL-GLUTAMINE FOR CDI TREATMENT (ACT) This study will examine the effectiveness and safety of Alanyl-glutamine addition to the standard treatment for CDI in preventing relapse or re-infection.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04305769

Alanyl-glutamine Supplementation for C. Difficile Treatment ... 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 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02053350

Alanyl-glutamine Supplementation of Standard Treatment ... We hypothesize that alanyl-glutamine when given with standard antibiotic treatment for C. difficile infection will decrease diarrhea, mortality and recurrent ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37474181/

a double-blind randomised controlled trial study protocol Alanyl-glutamine supplementation for Clostridioides difficile infection treatment (ACT): a double-blind randomised controlled trial study ...