Dietary Interventions for Cancer

Overseen By Hassane M Zarour, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Pittsburgh

Must be taking: Immune checkpoint inhibitors

Must not be taking: Antibiotics, Corticosteroids, Cytokines, others

Disqualifiers: Chronic alcohol, Major GI surgery, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 4

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot trial will study the potential impact of two distinct dietary interventions with sequential use of high-fermented foods and high-fiber supplements on the gut microbiome and antitumor immunity in patients with melanoma and non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors. The trial aims to understand how dietary changes affect the composition and function of the gut microbiome, together with immunological and metabolomic markers in serum in patients with melanoma and NSCLC who are undergoing standard-of-care treatment with a PD-1/PD-L1 Inhibitors (neoadjuvant, adjuvant or consolidation)

Will I have to stop taking my current medications?

The trial requires you to stop taking certain medications, such as systemic antibiotics, corticosteroids, cytokines, methotrexate, immunosuppressive agents, and probiotics or fiber supplements, at least 14 days before starting the diet. Additionally, systemic antibiotics and proton pump inhibitors must be discontinued more than 21 days prior to the study.

What data supports the effectiveness of the treatment Dietary Interventions, High-Fermented Food Diet, High-Fiber Supplements for cancer?

Research suggests that high fiber intake, particularly from vegetables, may be linked to lower colon cancer rates, and fiber fermentation in the gut produces beneficial compounds that could help prevent cancer. However, the evidence is mixed, and more studies are needed to fully understand the effects. ^{1 2 3 4 5}

Is it safe to use dietary interventions like high-fiber supplements and fermented foods for cancer prevention?

Research shows that while some dietary fibers may help reduce cancer risk, others, especially fermentable fibers, might increase tumor development in certain conditions. Additionally, some soluble fibers have been linked to liver issues and cancer in animal studies, so more research is needed to fully understand their safety. ^{2 4 5 6 7}

How does the dietary intervention treatment for cancer differ from other treatments?

This dietary intervention focuses on increasing fiber intake, which may help reduce cancer risk by promoting a healthy gut environment and reducing inflammation, unlike traditional cancer treatments that often involve medication or surgery. ^{1 2 4 5 8}

Research Team

Hassane M Zarour, MD

Principal Investigator

UPMC Hillman Cancer Center

Eligibility Criteria

This trial is for melanoma and NSCLC cancer patients undergoing standard immune checkpoint inhibitor therapy. It's designed to see if certain diets can help their treatment work better.

Inclusion Criteria

Be willing and able to provide written informed consent

Body mass index (BMI) 18.5-40 kg/m2

Patients must have any type of electronic device such as a smartphone, tablet, or computer etc that can access the internet

Exclusion Criteria

Current consumption of fiber ≥20g or fermented food ≥3 portions a day

I have not taken antibiotics or proton pump inhibitors in the last 21 days.

Pregnant or nursing (lactating) women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

High-Fermented Food Diet

Participants consume a high-fermented food diet to study its impact on gut microbiome and systemic inflammation

4 weeks

Weekly stool samples, blood samples every 2-4 weeks

Break/Observation

Participants have a break period where they can eat any type of food without dietary restrictions

2 weeks

High-Fiber Supplementation

Participants receive high-fiber supplementation to study its impact on gut microbiome and systemic inflammation

4 weeks

Weekly stool samples, blood samples every 2-4 weeks

Break/Observation

Participants have a break period where they can eat any type of food without dietary restrictions

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after dietary interventions

2 weeks

Treatment Details

Interventions

• Dietary Interventions

Trial Overview The study tests the effects of high-fermented foods and high-fiber supplements on gut bacteria and how they might boost the body's response to cancer immunotherapy in these patients.

Participant Groups

Group I: high-fermented food + high fiber supplementation Experimental Treatment 2 Interventions

Step 1: patients will consume high-fermented food Step 2: High fiber supplementation

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

Findings from Research

About 50% of cancer cases and 35% of cancer deaths in the U.S. are linked to Western dietary habits, highlighting the importance of nutrition in cancer prevention.

Optimizing diet by reducing caloric intake and fat (to 20% or less of total calories) while increasing fiber (to 25-35 g per day) can significantly lower cancer risk and promote overall health, as suggested by the Fiber First Diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diet and cancer prevention: the fiber first diet. Williams, GM., Williams, CL., Weisburger, JH.[2017]

High fiber consumption is generally associated with lower colon cancer rates in humans, particularly from cereal fiber sources, although case-control studies do not consistently confirm a protective effect from dietary fiber alone.

Laboratory studies indicate that poorly fermentable fibers like wheat bran may protect against colon cancer, while some fermentable fibers can actually enhance tumor development, suggesting that the type of fiber and its properties play a crucial role in cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between dietary fiber and cancer: metabolic, physiologic, and cellular mechanisms. Jacobs, LR.[2020]

In a study involving 75 healthy participants, supplementation with resistant starch (RS) and polydextrose for 50 days did not change fecal calprotectin levels, indicating no immediate inflammatory response in the gut.

Both RS and polydextrose significantly reduced the expression of SFRP1, which may lead to increased Wnt pathway activity, suggesting a potential mechanism by which these dietary fibers could influence colorectal cancer risk, although further research is needed to explore the functional effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of supplementation with nondigestible carbohydrates on fecal calprotectin and on epigenetic regulation of SFRP1 expression in the large-bowel mucosa of healthy individuals. Malcomson, FC., Willis, ND., McCallum, I., et al.[2023]

In a study involving 216 male Fischer 344 rats, certain dietary fibers like polydextrose and wheat bran significantly reduced colon tumor incidence compared to a control diet, suggesting their protective effects against tumorigenesis.

The study found that the fermentation characteristics of different carbohydrates play a crucial role in tumor outcomes, with specific fibers leading to fewer tumors and lower tumor burden in the colon, highlighting the importance of dietary fiber type in cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fermentable Carbohydrates Differentially Affect Colon Tumor Formation in Azoxymethane-Induced Male Fischer 344 Rats. Raju, J., Roberts, J., Chen, Q., et al.[2023]

This study is a double-blinded, randomized controlled trial involving 60 Alaska Native participants to assess whether dietary fiber supplementation can significantly reduce colorectal cancer risk, particularly in a population with the highest reported incidence of CRC.

Participants will be monitored for changes in inflammatory and proliferative biomarkers related to cancer risk after an 8-week period of fiber supplementation, with additional assessments of gut microbiota and metabolites, ensuring a comprehensive evaluation of the intervention's effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary fibre to reduce colon cancer risk in Alaska Native people: the Alaska FIRST randomised clinical trial protocol. Koller, KR., Wilson, A., Normolle, DP., et al.[2021]

In a study involving 96 rats, high-fiber diets containing resistant starch (RS) and short-chain fructo-oligosaccharides (FOS) were found to produce significant amounts of butyrate, which is linked to a healthier colon environment.

Rats fed these butyrate-producing diets showed a reduced number of aberrant crypt foci, a marker of potential colon cancer, suggesting that these specific fibers may help protect against colon carcinogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Only fibres promoting a stable butyrate producing colonic ecosystem decrease the rate of aberrant crypt foci in rats. Perrin, P., Pierre, F., Patry, Y., et al.[2019]

Fermentation of dietary soluble fibers by gut bacteria produces beneficial short-chain fatty acids (SCFAs) that support health and can serve as food supplements.

However, a study highlighted that while these fibers improve metabolic dysfunction, they may also induce cholestasis and increase the risk of hepatocellular carcinoma (HCC), indicating a complex relationship between fiber intake and liver health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When Soluble Fibers Meet Hepatocellular Carcinoma: The Dark Side of Fermentation. Gallage, S., Kotsiliti, E., Heikenwalder, M.[2018]

A high-fiber diet is associated with a reduced risk of several cancers, particularly colon cancer, with 25 out of 32 studies showing this protective effect since 1980.

While many studies indicate that fiber-rich foods may lower cancer risk, it's challenging to determine if fiber alone is responsible for this effect, suggesting that overall dietary patterns are more important than just fiber supplements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary fiber and cancer prevention. Shankar, S., Lanza, E.[2017]

References

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

Diet and cancer prevention: the fiber first diet. [2017]

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

Relationship between dietary fiber and cancer: metabolic, physiologic, and cellular mechanisms. [2020]

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

Effects of supplementation with nondigestible carbohydrates on fecal calprotectin and on epigenetic regulation of SFRP1 expression in the large-bowel mucosa of healthy individuals. [2023]

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

Fermentable Carbohydrates Differentially Affect Colon Tumor Formation in Azoxymethane-Induced Male Fischer 344 Rats. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Dietary fibre to reduce colon cancer risk in Alaska Native people: the Alaska FIRST randomised clinical trial protocol. [2021]

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

Only fibres promoting a stable butyrate producing colonic ecosystem decrease the rate of aberrant crypt foci in rats. [2019]

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

When Soluble Fibers Meet Hepatocellular Carcinoma: The Dark Side of Fermentation. [2018]

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

Dietary fiber and cancer prevention. [2017]