Specialized Diets for Clostridium Difficile Infection

Overseen By Alexander Khoruts, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

Must not be taking: Antibiotics

Disqualifiers: IBD, Stomach surgery, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how special diets can aid recovery for individuals with repeated Clostridioides difficile infections (rCDI) who are also receiving fecal microbiota transplants (FMT). Researchers are testing two diets: the MEND diet (Microbiota Enhancing and Nourishing Diet), which supports gut health, and the mNICE diet, a modified version of a known gut-friendly diet. The goal is to determine which diet more effectively enhances gut health after FMT. Individuals who have experienced at least two rCDI recurrences in one year and plan to undergo FMT might be eligible. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on diet and gut health.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are expected to take antibiotics during the study, you would be excluded from participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that diet can greatly affect the outcomes of Clostridioides difficile infections (CDI). The MEND diet, tested mainly in animals, appears promising for influencing CDI outcomes. However, limited information exists on its effects in humans, so researchers are still learning about its safety and tolerability.

For the mNICE diet, animal studies suggest that increased carbohydrate intake might protect against CDI. Additionally, diets higher in fiber and lower in fat could help prevent CDI recurrence. Yet, most findings come from animal studies, necessitating further research to determine the safety and effectiveness of these diets in humans.

In summary, both diets show potential, but more human studies are needed to confirm their safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the MEND and mNICE diets because they offer a fresh approach to managing Clostridium difficile infections. Traditional treatments often rely on antibiotics, which can disrupt gut flora. In contrast, these diets are paired with Fecal Microbiota Transplantation (FMT), a method that introduces healthy bacteria into the gut to restore balance. By using FMT alongside specialized diets, there's potential to not only treat the infection more effectively but also reduce recurrence rates, offering a sustainable solution to this stubborn condition.

What evidence suggests that this trial's diets could be effective for recurrent Clostridioides difficile infection?

Research shows that diet plays a crucial role in managing Clostridioides difficile infections (CDI). Studies have found that a high-fiber, low-fat diet can help prevent CDI recurrence. In this trial, participants will follow one of two dietary interventions. The MEND diet, one study arm, focuses on improving gut health by supporting beneficial intestinal bacteria. The mNICE diet, another study arm, is a modified version with the same goal of supporting gut health. Both diets are designed to complement fecal microbiota transplants (FMTs), which effectively treat recurring CDI. Evidence suggests that combining these diets with FMT may improve patient outcomes. ^{1 2 3 4 6}

Who Is on the Research Team?

Alexander Khoruts, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for adults at least 18 years old who have had two or more recurrences of Clostridium difficile infection within a year and are planning to undergo fecal microbiota transplant (FMT) therapy. Participants must be able to follow the study requirements and give informed consent.

Inclusion Criteria

Informed consent

Ability to comply with study requirements

I am planning to have FMT therapy for recurring C. diff infection.

Exclusion Criteria

Ongoing alcohol or drug abuse

Pregnancy

Any reason felt by the investigator to complicate the feasibility of participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive FMT and follow a specific diet (MEND or mNICE) to optimize microbiome recovery

4 weeks

Weekly visits for dietary monitoring and FMT administration

Follow-up

Participants are monitored for safety and effectiveness of the diet and FMT on microbiome recovery

3 months

Monthly visits for microbiome assessment

What Are the Treatments Tested in This Trial?

Interventions

• MEND diet
• mNICE diet

Trial Overview

The trial is testing two diets, MEND and mNICE, designed to optimize gut health after FMT in patients with recurrent C. difficile infections. The goal is to see how well these diets support recovery by nourishing the new microbiome established by FMT.

How Is the Trial Designed?

Group I: MEND diet Experimental Treatment 1 Intervention

patients being treated with FMT

Group II: mNICE (modified NICE) diet Active Control 1 Intervention

patients being treated with FMT

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Published Research Related to This Trial

C. difficile is a significant pathogen that can cause a range of conditions from asymptomatic carriage to severe colitis, with higher carriage rates in long-term care facilities (20-50%).

The study highlights a successful case where dietary modification was used to treat C. difficile colonization and recurrence, suggesting that diet may play a crucial role in managing this infection by influencing the gut microbiome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary therapy for clostridium difficile colonization: A case series. Suskind, DL., Lee, D., Solan, P., et al.[2020]

Daily administration of the probiotic kefir, combined with a staggered and tapered antibiotic withdrawal regimen, may effectively resolve recurrent Clostridium difficile infections.

This approach could be as effective as fecal microbiota transplantation, suggesting a potential alternative treatment for this challenging infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Staggered and tapered antibiotic withdrawal with administration of kefir for recurrent Clostridium difficile infection. Bakken, JS.[2020]

In a mouse model of antibiotic-induced Clostridioides difficile infection (CDI), high-fat/high-protein diets significantly worsened CDI outcomes, leading to 100% mortality with an Atkins-like diet, while a high-carbohydrate diet provided protection against CDI.

The study suggests that high-fat diets may promote CDI by reducing beneficial gut bacteria that compete with C. difficile, whereas high-carbohydrate diets may help maintain these protective bacteria, highlighting the importance of diet in managing CDI risk during antibiotic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A High-Fat/High-Protein, Atkins-Type Diet Exacerbates Clostridioides (Clostridium) difficile Infection in Mice, whereas a High-Carbohydrate Diet Protects. Mefferd, CC., Bhute, SS., Phan, JR., et al.[2021]

In a study using a murine model of Clostridium difficile infection (CDI), dietary supplementation with indole-3-carbinol (I3C) significantly reduced disease severity and mortality compared to a diet lacking this AHR ligand, indicating its potential as a therapeutic option.

I3C appears to enhance immune responses by increasing specific immune cell populations without causing additional inflammation, suggesting it may work through both AHR-dependent and independent mechanisms to help combat CDI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amelioration of Clostridium difficile Infection in Mice by Dietary Supplementation With Indole-3-carbinol. Julliard, W., De Wolfe, TJ., Fechner, JH., et al.[2020]

Mice on a high-fat/low-fiber 'Western-type' diet showed significantly increased mortality from Clostridioides difficile infection (CDI) compared to those on a low-fat/low-fiber diet, suggesting that diet plays a crucial role in CDI outcomes.

The high-fat diet altered bile acid composition, leading to a lack of protective secondary bile acids and an increase in the harmful toxin TcdA, indicating that dietary modifications could be an effective strategy for preventing CDI in at-risk populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary fat promotes antibiotic-induced Clostridioides difficile mortality in mice. Hazleton, KZ., Martin, CG., Orlicky, DJ., et al.[2022]

In a study of 10 patients with recurrent C. difficile infection, all participants experienced successful resolution of diarrhea after receiving fecal microbiota transplants, indicating the efficacy of this treatment.

Post-transplant, recipients showed significant increases in microbiota diversity and restoration of secondary bile acid levels, which are associated with resistance to C. difficile growth, highlighting the mechanism by which fecal transplants can help restore gut health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in microbiota composition, bile and fatty acid metabolism, in successful faecal microbiota transplantation for Clostridioides difficile infection. Brown, JR., Flemer, B., Joyce, SA., et al.[2020]

In a mouse model of Clostridium difficile infection (CDI), diets rich in microbiota-accessible carbohydrates (MACs) significantly reduced the severity and duration of CDI, suggesting that dietary changes can influence gut health and pathogen behavior.

The study found that MACs promote beneficial gut bacteria that produce short-chain fatty acids, which help suppress C. difficile growth, even though the bacteria may still produce toxins; this highlights the potential of MAC-focused diets as a strategy to combat CDI, especially given the fiber deficiencies in typical Western diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbiota-accessible carbohydrates suppress Clostridium difficile infection in a murine model. Hryckowian, AJ., Van Treuren, W., Smits, SA., et al.[2021]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12247793/

The Impact of Diet on Clostridioides difficile Infection

Although much of the data currently originates from animal models, there is growing evidence of the ability of diet to impact CDI-related outcomes. This review ...

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withpower.com

withpower.com/clinical-trials/for-clostridium-difficile

Top Clostridium Difficile Clinical Trials | Power

This trial is testing if a diet with more fiber and less fat can help prevent C. difficile infections from coming back in cancer patients. The idea is that this ...

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The Impact of Diet on Clostridioides difficile Infection: A Review

This review aims to enrich the understanding of dietary components that impact C. difficile metabolism and pathogenesis, as well as provide limitations in the ...

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JID for Clinicians: Influences of the human gut microbiome ...

The Impact of Diet on Clostridioides difficile Infection: A Review. C. difficile's metabolism and pathogenesis are strongly influenced by ...

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contagionlive.com/view/microbiota-based-therapies-show-superior-outcomes-for-recurrent-c-difficile-infection

Microbiota-Based Therapies Show Superior Outcomes for ...

Systematic review finds FMT and standardized microbiome products outperform antibiotics in efficacy and safety.

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Clostridioides difficile Infection: Is There a Role for Diet and ...

There is a paucity of high-quality clinical trial data of probiotics in CDI, and most studies are underpowered, with CDI as a secondary outcome in studies done ...