Specialized Diets for Clostridium Difficile Infection

Recruiting in Palo Alto (17 mi)

Overseen by Alexander Khoruts, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Minnesota

Must not be taking: Antibiotics

Disqualifiers: IBD, Stomach surgery, Liver disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Recurrent Clostridioides difficle infection (rCDI) is a very significant problem in its own right and current fecal microbiota transplant (FMT) -based therapeutics will benefit from their optimization for this indication. It is likely that appropriate nutritional support coupled with microbiota-based drugs will yield superior clinical outcomes. However, both diet and gut microbiome are very complex. This project, which is based on a wealth of FMT experience, both clinical and investigational, over the past decade along with the novel techniques developed to identify dietary patterns and food groups that explain the most variation in gut microbiome, offers an ideal platform for performing systematic research in nutritional support that promotes gut microbiota health. The purpose is to Generate preliminary data with regards to tolerability of the Microbiota enhancing and nourishing diet (MEND) and its effects on the fecal microbiota in rCDI patients following FMT with the goal of developing larger clinical trials aimed to optimize post-FMT dietary management.

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.

What data supports the effectiveness of the MEND diet treatment for Clostridium Difficile Infection?

Research suggests that dietary changes can impact the gut microbiome, which is important in managing Clostridium difficile infection. A high-carbohydrate diet has been shown to protect against this infection in mice, indicating that certain dietary modifications, like those in the MEND diet, might help manage the condition. ^{1 2 3 4 5}

Is the MEND diet safe for humans?

Research on specialized diets for Clostridium difficile infection (CDI) in mice suggests that high-fat diets can worsen CDI, while high-carbohydrate diets may offer protection. Although these findings are from animal studies, they highlight the potential impact of diet on gut health and CDI, suggesting that dietary interventions could be safe and beneficial, but human studies are needed for confirmation. ^{1 2 3 6 7}

How does the specialized diet treatment for Clostridium difficile infection differ from other treatments?

This specialized diet treatment for Clostridium difficile infection is unique because it focuses on dietary modifications, particularly increasing high-carbohydrate and microbiota-accessible carbohydrates (MACs), which can protect against the infection by promoting beneficial gut bacteria and reducing harmful ones. Unlike traditional treatments that often involve antibiotics, this approach uses diet to influence gut health and reduce infection risk. ^{1 2 3 6 7}

Research Team

Alexander Khoruts, MD

Principal Investigator

University of Minnesota

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• MEND diet (Dietary Supplement)
• mNICE diet (Dietary Supplement)

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.

Participant Groups

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+

Shashank Priya

University of Minnesota

Chief Executive Officer since 2023

PhD in Materials Engineering from Penn State

Charles Semba

University of Minnesota

Chief Medical Officer since 2021

MD from the University of Minnesota Medical School

Findings from Research

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]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Dietary therapy for clostridium difficile colonization: A case series. [2020]

2. United States 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. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Amelioration of Clostridium difficile Infection in Mice by Dietary Supplementation With Indole-3-carbinol. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Changes in microbiota composition, bile and fatty acid metabolism, in successful faecal microbiota transplantation for Clostridioides difficile infection. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Microbiota-accessible carbohydrates suppress Clostridium difficile infection in a murine model. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Dietary fat promotes antibiotic-induced Clostridioides difficile mortality in mice. [2022]