Exploring the Effects of a High Chlorophyll Dietary Intervention to Reduce Colon Cancer Risk in Adults

NCT03582306 | Completed

• 1 other identifier: AU-18-208
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Colon cancer is the third most common cancer in men and women and over 70% of cases are preventable. A western diet, characterized by low vegetable and high red and processed meat intake, indisputably increases colon cancer risk. Heme, which gives red meat its color, is highly reactive, induces hyperproliferation and promotes DNA damage in the colon to a greater degree than any other red meat-associated carcinogen. Preclinical models indicate dietary chlorophyll, which gives green leafy vegetables their color, binds and stabilizes heme in the lumen, preventing genotoxicity. Additionally, data from our randomized controlled weight loss trial indicate increasing red meat consumption has deleterious effects on the gut microbiome, which is also implicated in colon cancer etiology. Because heme-containing foods are the richest sources of bioavailable iron and several other vitamins and minerals, mitigating their potential risks may be more beneficial than eliminating meat, poultry, fish and seafood in their entirety from the diet for risk reduction. This feasibility study will begin to explore the research question: Will adding chlorophyll-rich green leafy vegetables to the diet prevent the deleterious effects of heme-rich red meat on the human host and microbiome? The investigators will randomly assign 50 adults at increased risk of colorectal adenoma to a block randomized crossover study with two 4-week dietary regimens in which: 1) participants will be provided with frozen green leafy vegetables and counseled to consume a high chlorophyll diet including 1 cup per day of cooked green leafy vegetables and normal meat (high heme) consumption; or 2) continue their normal high heme, low chlorophyll diet (control). A 4-week washout period encouraging habitual diet will be employed between the intervention periods and data will be collected at all four time points. This study is critical in translating preclinical findings and has the potential to open the door to new knowledge and standards of care in colon cancer prevention. This study is a required step to aid in the design of a larger RCT to determine whether increased green leafy vegetable consumption mitigates the negative effects of red meat on DNA damage, inflammatory cytokines and gut microbe composition. This could lead to equally beneficial dietary guidance for colon health that might be more easily attained by the general public through addition, rather than omission of specific foods.

Conditions

Colon Cancer Prevention

Keywords

colon cancer; dietary intervention; vegetables; microbiota

Outcome Measures

Primary Outcomes (3)

• Feasibility - accrual

  Accrue 50 participants

  9 months

• Feasibility - retention

  Retain 90% of sample at crossover and 80% at completion

  12 weeks

• Feasibility - adherence

  Meet chlorophyll intake goals 90% of days

  4 weeks during intervention phase

Secondary Outcomes (8)

• DNA damage

  Change from baseline to 4 weeks and 8 weeks to 12 weeks

• Inflammatory marker - C-Reactive Protein

  Change from baseline to 4 weeks and 8 weeks to 12 weeks

• Inflammatory marker - Tumor Necrosis Factor-alpha

  Change from baseline to 4 weeks and 8 weeks to 12 weeks

• Inflammatory marker - Interleukin 6

  Change from baseline to 4 weeks and 8 weeks to 12 weeks

• Gut microbe composition

  Change from baseline to 4 weeks and 8 weeks to 12 weeks

Study Arms (2)

High chlorophyll diet - intervention 1st

EXPERIMENTAL

Participants will complete the 4 week intervention, 4 week washout, then 4 week control period (monitor only)

Behavioral: High chlorophyll diet - intervention 1st

High chlorophyll diet - control 1st

EXPERIMENTAL

Participants will complete the 4 week control period (monitor only), 4 week washout, then 4 week intervention

Behavioral: High chlorophyll diet - control 1st

Interventions

High chlorophyll diet - intervention 1st BEHAVIORAL

Participants will be provided frozen dark leafy green vegetables, and counseled to consume 1 cup cooked dark green leafy vegetables (2 servings) daily over the 4 week period while maintaining their normal red meat intake. This will occur during the first 4 week period of the study.

Also known as: High green leafy vegetable diet

High chlorophyll diet - intervention 1st

High chlorophyll diet - control 1st BEHAVIORAL

Participants will be provided frozen dark leafy green vegetables, and counseled to consume 1 cup cooked dark green leafy vegetables (2 servings) daily over the 4 week period while maintaining their normal red meat intake. This will occur during the last 4 week period of the study.

Also known as: High green leafy vegetable diet

High chlorophyll diet - control 1st

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Consume less than 2 servings of green leafy vegetables per day
• Consume 5 or more servings of red meat per week
• BMI \>30 kg/m2
• Agrees to not change dietary supplements during course of study
• Willing to comply with dietary regimen over course of study
• Able to store and cook frozen green leafy vegetables (freezer and microwave)
• Able to speak and read English

You may not qualify if:

• Previous diagnosis of colon cancer
• Use of any of the following in the past 4 weeks: systemic antibiotics, corticosteroids, immunosuppressive agents, commercial probiotics

Sponsors & Collaborators

• Auburn University: lead

Study Sites (1)

Auburn University

Auburn, Alabama, 36849, United States

Location

Related Publications (4)

• Fruge AD, Ptacek T, Tsuruta Y, Morrow CD, Azrad M, Desmond RA, Hunter GR, Rais-Bahrami S, Demark-Wahnefried W. Dietary Changes Impact the Gut Microbe Composition in Overweight and Obese Men with Prostate Cancer Undergoing Radical Prostatectomy. J Acad Nutr Diet. 2018 Apr;118(4):714-723.e1. doi: 10.1016/j.jand.2016.10.017. Epub 2016 Dec 15.

  PMID: 27988219 BACKGROUND

• Fruge AD, Van der Pol W, Rogers LQ, Morrow CD, Tsuruta Y, Demark-Wahnefried W. Fecal Akkermansia muciniphila Is Associated with Body Composition and Microbiota Diversity in Overweight and Obese Women with Breast Cancer Participating in a Presurgical Weight Loss Trial. J Acad Nutr Diet. 2020 Apr;120(4):650-659. doi: 10.1016/j.jand.2018.08.164. Epub 2018 Nov 9.

  PMID: 30420171 BACKGROUND

• Fruge AD, Smith KS, Riviere AJ, Demark-Wahnefried W, Arthur AE, Murrah WM, Morrow CD, Arnold RD, Braxton-Lloyd K. Primary Outcomes of a Randomized Controlled Crossover Trial to Explore the Effects of a High Chlorophyll Dietary Intervention to Reduce Colon Cancer Risk in Adults: The Meat and Three Greens (M3G) Feasibility Trial. Nutrients. 2019 Oct 2;11(10):2349. doi: 10.3390/nu11102349.

  PMID: 31581743 RESULT

• Riviere AJ, Smith KS, Schaberg MN, Greene MW, Fruge AD. Plasma and fecal zonulin are not altered by a high green leafy vegetable dietary intervention: secondary analysis of a randomized control crossover trial. BMC Gastroenterol. 2022 Apr 12;22(1):184. doi: 10.1186/s12876-022-02248-3.

  PMID: 35413837 DERIVED

Related Links

• Meat and Three Greens website and link to eligibility survey

MeSH Terms

Conditions

Colonic Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Andrew D Fruge, PhD, RD

  Auburn University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor and Director, Didactic Program in Dietetics

Model Details: 4 week intervention and control periods will be delivered and separated by a 4 week washout. The order of intervention and control periods will be randomly allocated

Study Record Dates

• First Submitted: June 10, 2018
• First Posted: July 11, 2018
• Study Start: July 23, 2018
• Primary Completion: December 12, 2018
• Study Completion: December 12, 2018
• Last Updated: October 15, 2019

Record last verified: 2019-10

Locations

US (1)