Mediterranean Diet + Lifestyle Changes for Colorectal Cancer Prevention

(Bridge CRC Trial)

Overseen By Lara Blumstein

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Illinois at Chicago

Must not be taking: Antibiotics, Prebiotics, Probiotics, Laxatives

Disqualifiers: Renal disease, Autoimmune disorders, Cancer, others

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

Compensation: Varies

Number of Visits: 4

232 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

A Mediterranean Diet (MedDiet), a largely plant-based dietary pattern, is relevant to CRC prevention and microbial production of anti-cancer metabolites in observational studies. A MedDiet can shift BA metabolism as shown in primates and when combined with calorie restriction, shows superior adherence and weight control in humans, given its palatability. To date, no studies have tested in an RCT the effects of a MedDiet alone (MedA), WL through lifestyle intervention (WL-A) or a calorie-restricted MedDiet for WL (WL-Med) on the BA-gut microbiome axis and its relevance to CRC prevention among AAs. A multidisciplinary team combining expertise in psychology, nutrition, microbiology, molecular cell biology, computational biology, medicine and biostatistics, proposes to conduct a four-arm RCT in which 232 obese AAs, 45-75 years old complete one of the following 6-month interventions: Med-A, weight stable; WL-A, calorie restriction with no diet pattern change; WLMed; or Control. The investigators will use samples and data collected at baseline, mid-study (month-3) and post-intervention to compare the effects of the interventions on 1) Concentration and composition of circulating and fecal BAs; 2) Gut microbiota and metabolic function; and 3) Gene expression profiles of exfoliated intestinal epithelial cells.

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, it does list certain health conditions and treatments that would exclude you from participating, so it's best to discuss your specific medications with the trial coordinators.

Is the Mediterranean Diet safe for humans?

The Mediterranean Diet is generally considered safe for humans and is associated with various health benefits, including protection against heart disease, diabetes, obesity, and some cancers. It is known for its anti-inflammatory and antioxidant properties, and no significant safety concerns have been reported in the studies reviewed. ^{1 2 3 4 5}

How does the Mediterranean Diet and lifestyle changes treatment for colorectal cancer prevention differ from other treatments?

The Mediterranean Diet and lifestyle changes treatment is unique because it focuses on dietary patterns rich in extra virgin olive oil and other bioactive food components that may prevent colorectal cancer by influencing biological mechanisms like inflammation and the microbiome, rather than relying on medication or surgery. ^{1 3 5 6 7}

What data supports the effectiveness of the Mediterranean Diet and lifestyle changes as a treatment for colorectal cancer prevention?

Research shows that following a Mediterranean diet, which includes lots of fruits, vegetables, and healthy fats, can help protect against colorectal cancer. This diet has been linked to lower cancer risk and is beneficial for heart health and diabetes prevention. ^{1 3 5 8 9}

Who Is on the Research Team?

Lisa Tussing-Humphreys, PhD, RD

Principal Investigator

University of Illinois at Chicago

Marian Fitzgibbon, PhD

Principal Investigator

University of Illinois at Chicago

Are You a Good Fit for This Trial?

This trial is for African American men and women aged 45-75 with a BMI of 30-50, willing to follow diet interventions or maintain current habits as assigned. Exclusions include autoimmune, severe heart or lung diseases, recent cancer treatment, certain genetic risks for colorectal cancer (CRC), substance abuse, uncontrolled diabetes, and other specific health conditions.

Inclusion Criteria

Plans to reside in Chicago for the next 8-10 months.

Has access to a phone

I am willing and able to give my consent for treatment.

Exclusion Criteria

I have had weight loss surgery in the past.

Combustible tobacco use

I have taken antibiotics in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Participants undergo one of four 6-month interventions: Med-A, WL-A, WL-Med, or Control, focusing on diet and weight loss strategies

6 months

1 initial in-person session, followed by 24 weekly sessions (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with data collection at baseline, mid-study, and post-intervention

6 months

3 visits (in-person or virtual) at baseline, month-3, and month-6

What Are the Treatments Tested in This Trial?

Interventions

• Mediterranean Diet
• Weight Loss

Trial Overview The study tests the effects of a Mediterranean Diet alone (Med-A), weight loss through lifestyle changes without diet pattern change (WL-A), calorie-restricted MedDiet for weight loss (WL-Med) versus control on bile acids and gut microbiome related to CRC prevention in obese individuals over six months.

How Is the Trial Designed?

Group I: WL-Med Experimental Treatment 2 Interventions

WL-Med will attend a one-hour, in-person session with a registered dietitian (RD) prior to the intervention. The RD will instruct on an eating pattern consistent with a MedDiet using an individualized exchange list. Exchanges are based on individual caloric needs to lose weight (WL-Med, calorie restriction to achieve a 1-2 lb. per week WL and 5% WL from baseline at 6 months). We will not ask subjects to abstain from alcohol despite its known effects on BA metabolism, but we will recommend that only 5% of calories come from alcohol taken with meals. Following the initial session, subjects will meet remotely or in-person for 24 individual sessions (1-hour, held approximately weekly). Additional asynchronous learning materials will be distributed weekly through a private Facebook group. The WL-Med group will be prescribed an activity program. Some asynchronous lessons will contain information about physical activity. Physical activity will be monitored via FitBit.

Group II: WL-A Experimental Treatment 1 Intervention

WL-A will attend a one-hour, in-person individual session with a registered dietitian (RD) during the two weeks prior to the intervention. For WL-A, the focus will be on daily calorie restriction (-500-750 kcal/day) to achieve a 1-2 lb. per week WL and 5% WL from baseline at 6 months in the context of the subject's typical diet pattern. We will not ask subjects to abstain from alcohol during the trial despite its known effects on BA metabolism, but we will recommend that only 5% of calories come from alcohol taken with meals. Following the initial session, subjects will meet for 24 individual, virtual or in-person sessions (1-hour, held approximately weekly) over the remaining 6 months. Additional asynchronous learning materials will be distributed weekly through a private Facebook group. The WL-A group will be prescribed an activity program. Physical activity will be monitored via FitBit.

Group III: Med-A Experimental Treatment 1 Intervention

Med-A will attend a one-hour, in-person individual session with a registered dietitian (RD) during the two weeks prior to the start of the intervention. For subjects randomized to Med-A the study RD will instruct on adoption of an eating pattern consistent with a MedDiet using an individualized MedDiet exchange list and companion guide. Recommended daily exchanges are based on individual caloric needs to maintain weight. We will not ask subjects to abstain from alcohol during the trial despite its known effects on BA metabolism, but we will recommend that only 5% of calories come from alcohol taken with meals. Following the initial session, subjects will meet for 24 individual sessions (1-hour, held approximately weekly) in-person or virtually over the remaining 6 months. Additional asynchronous learning materials will be distributed weekly through a private Facebook group. The Med-A group will be asked to maintain their usual physical activity.

Group IV: Control Active Control 1 Intervention

The study RD will meet individually with the Control group subjects in-person for 1-hour at the start of the 6-month intervention. Control participants will be instructed to maintain current eating and activity patterns and weight over the next 6 months. No dietary recommendations are provided, and they will receive weekly health newsletters that include non-diet related health topics (e.g., flu prevention). Contact will be made again at month-3 and post-intervention (month-6) research visits and during monthly phone calls to collect data pertaining to recent diet intake. At the month-3 assessment, weight will be checked and those with \>2.5% WL from baseline will receive additional instruction from the RD to maintain lifestyle patterns. All WL-Med materials are offered to the group in a self-guided format following the 6-month intervention.

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 500 participants (250 with colorectal cancer and 250 controls), adherence to the Mediterranean diet was found to have a protective effect against colorectal cancer, regardless of the presence of metabolic syndrome.

Factors such as metabolic syndrome, age, smoking, and family history of colorectal cancer increased the risk, while following the Mediterranean diet significantly reduced the risk, highlighting its potential as a dietary intervention for cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic syndrome and colorectal cancer: the protective role of Mediterranean diet--a case-control study. Kontou, N., Psaltopoulou, T., Soupos, N., et al.[2017]

The Mediterranean diet (MD) is linked to various health benefits, including a potential protective effect against colorectal cancer (CRC), which primarily develops through a long-term process that offers a significant opportunity for prevention.

This review highlights the biological mechanisms by which components of the MD may prevent CRC, emphasizing the importance of dietary patterns in reducing cancer risk and suggesting future research directions related to epigenetics and the microbiome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mediterranean Diet: Prevention of Colorectal Cancer. Donovan, MG., Selmin, OI., Doetschman, TC., et al.[2022]

Adherence to the Mediterranean diet is associated with a lower incidence of colorectal cancer (CRC), with a summary relative risk (RR) of 0.90 for those with the highest adherence compared to the lowest, based on 13 prospective cohort studies.

While the Mediterranean diet shows a protective effect against CRC incidence, it does not significantly impact overall mortality or CRC-specific mortality in diagnosed patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between Mediterranean diet adherence and colorectal cancer: a dose-response meta-analysis. Zhong, Y., Zhu, Y., Li, Q., et al.[2023]

In a study of 35,372 women followed for an average of 17.4 years, adherence to the Mediterranean diet was associated with a reduced risk of colorectal cancer, particularly rectal cancer, with a significant hazard ratio of 0.38 for those with the highest adherence compared to the lowest.

For every 2-point increase in the Mediterranean diet score, there was a 12% reduction in the risk of colorectal cancer (HR = 0.88), indicating that following this dietary pattern may be beneficial for cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Mediterranean diet and risk of colorectal cancer in the UK Women's Cohort Study. Jones, P., Cade, JE., Evans, CEL., et al.[2022]

The systematic review of 117 studies involving over 3.2 million participants found that high adherence to the Mediterranean diet is associated with a lower risk of cancer mortality and all-cause mortality among cancer survivors.

Specifically, the Mediterranean diet was linked to reduced risks for several types of cancer, including colorectal, head and neck, respiratory, gastric, liver, and bladder cancers, although it did not affect the risk of blood, esophageal, pancreatic, and prostate cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An updated systematic review and meta-analysis on adherence to mediterranean diet and risk of cancer. Morze, J., Danielewicz, A., Przybyłowicz, K., et al.[2021]

The Mediterranean Diet (MedDiet) has been linked to numerous health benefits, particularly in reducing the risk of cardiovascular diseases, metabolic disorders, and cancer, as evidenced by an increase in clinical trials over the last decade.

The diet's positive effects are largely attributed to its anti-inflammatory and antioxidant properties, with strict adherence and specific components like olive oil playing crucial roles in managing obesity and waist circumference.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Mediterranean Diet: An Update of the Clinical Trials. Finicelli, M., Di Salle, A., Galderisi, U., et al.[2022]

In a study of 132 colorectal cancer cases in Southern Italy, high consumption of refined sugar and excessive wine intake were associated with significantly increased risks of developing colorectal cancer, with relative risks of 2.75 and 3.22, respectively.

Conversely, high consumption of raw and cooked vegetables, dairy products, and more than two cups of coffee per day were linked to a reduced risk of colorectal cancer, suggesting that a Mediterranean dietary pattern may contribute to lower cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary habits and colorectal cancer in a low-risk area. Results from a population-based case-control study in southern Italy. Centonze, S., Boeing, H., Leoci, C., et al.[2015]

Pinoresinol-rich extracts from extra virgin olive oil (EVOO-A) showed significant anticancer properties, particularly in p53-proficient colorectal cancer cell lines, leading to increased apoptosis and cell cycle arrest.

The study suggests that the combination of phenolic compounds in EVOO may work synergistically, enhancing the chemopreventive effects at lower concentrations compared to purified pinoresinol, which requires higher doses to achieve similar effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemopreventive properties of pinoresinol-rich olive oil involve a selective activation of the ATM-p53 cascade in colon cancer cell lines. Fini, L., Hotchkiss, E., Fogliano, V., et al.[2022]

In a study of 132,746 participants followed for up to 26 years, adherence to the DASH diet was linked to a 20% lower risk of total colorectal cancer, indicating its potential protective effect against this disease.

The DASH diet also showed a significant association with a reduced risk of colon cancer (19% lower risk) and a trend towards lower risk for rectal cancer, while no significant association was found with the Alternate Mediterranean Diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets and colorectal cancer. Fung, TT., Hu, FB., Wu, K., et al.[2023]

Citations

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

Metabolic syndrome and colorectal cancer: the protective role of Mediterranean diet--a case-control study. [2017]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Mediterranean Diet: Prevention of Colorectal Cancer. [2022]

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

Association between Mediterranean diet adherence and colorectal cancer: a dose-response meta-analysis. [2023]

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

The Mediterranean diet and risk of colorectal cancer in the UK Women's Cohort Study. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

An updated systematic review and meta-analysis on adherence to mediterranean diet and risk of cancer. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

The Mediterranean Diet: An Update of the Clinical Trials. [2022]

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

Dietary habits and colorectal cancer in a low-risk area. Results from a population-based case-control study in southern Italy. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Chemopreventive properties of pinoresinol-rich olive oil involve a selective activation of the ATM-p53 cascade in colon cancer cell lines. [2022]

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

The Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets and colorectal cancer. [2023]