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Exploring the Effects of a High Chlorophyll Dietary Intervention to Reduce Colon Cancer Risk in Adults (M3G)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03582306
Recruitment Status : Completed
First Posted : July 11, 2018
Last Update Posted : October 15, 2019
Sponsor:
Information provided by (Responsible Party):
Andrew Fruge, Auburn University

Tracking Information
First Submitted Date  ICMJE June 10, 2018
First Posted Date  ICMJE July 11, 2018
Last Update Posted Date October 15, 2019
Actual Study Start Date  ICMJE July 23, 2018
Actual Primary Completion Date December 12, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 10, 2018)
  • Feasibility - accrual [ Time Frame: 9 months ]
    Accrue 50 participants
  • Feasibility - retention [ Time Frame: 12 weeks ]
    Retain 90% of sample at crossover and 80% at completion
  • Feasibility - adherence [ Time Frame: 4 weeks during intervention phase ]
    Meet chlorophyll intake goals 90% of days
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2018)
  • DNA damage [ Time Frame: Change from baseline to 4 weeks and 8 weeks to 12 weeks ]
    Serum 8-hydroxy-2'-deoxyguanosine
  • Inflammatory marker - C-Reactive Protein [ Time Frame: Change from baseline to 4 weeks and 8 weeks to 12 weeks ]
    Serum hsCRP
  • Inflammatory marker - Tumor Necrosis Factor-alpha [ Time Frame: Change from baseline to 4 weeks and 8 weeks to 12 weeks ]
    Serum TNF-alpha
  • Inflammatory marker - Interleukin 6 [ Time Frame: Change from baseline to 4 weeks and 8 weeks to 12 weeks ]
    Serum IL-6
  • Gut microbe composition [ Time Frame: Change from baseline to 4 weeks and 8 weeks to 12 weeks ]
    16s changes in microbiota alpha diversity
  • Bile acids [ Time Frame: Change from baseline to 4 weeks and 8 weeks to 12 weeks ]
    Plasma primary and secondary bile acids
  • Body composition [ Time Frame: Change from baseline to 4 weeks and 8 weeks to 12 weeks ]
    Body fat percentage using Bioelectrical Impedence Analysis
  • Acceptability [ Time Frame: 4 weeks during intervention phase ]
    Acceptability of the diets will be measured by the Food Acceptability Questionnaire (FAQ) total score. The FAQ is a 10 item questionnaire scored on a 7-point likert scale with total scores ranging from 7-70.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Exploring the Effects of a High Chlorophyll Dietary Intervention to Reduce Colon Cancer Risk in Adults
Official Title  ICMJE Exploring the Effects of a High Chlorophyll Dietary Intervention to Reduce Colon Cancer Risk in Adults: The Meat and Three Greens Feasibility Trial
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.

Detailed Description

Fifty thousand cases of colon and rectal cancer (CRC) could be prevented each year through screening, increased exercise and improved diet. Obesity alone increases risk of CRC by 33% and is associated with increased CRC mortality. Red and processed meat consumption is associated with increased CRC risk, most often in the context of dietary patterns, which juxtapose "Western" and "prudent" diets. A recent meta-analysis of 24 case control studies and 11 prospective cohort studies (n=1,295,063 men and women) found an 18% reduction in risk for colon cancer in the groups consuming the highest levels of cruciferous and green leafy vegetables. Risk reduction with high green leafy vegetable consumption remained significant regardless of whether pooled studies controlled for meat and/or total energy intake.

Heme-induced genotoxicity of the colon is prevented by chlorophyll in rodent models; an important finding that has not been tested in clinical trials though is supported by epidemiological observation.

This trial utilizes a crossover design to assess the feasibility of a dietary intervention in adults at increased risk of CRC. The overall intent of this line of research is to elucidate a CRC risk-reducing dietary pattern that is accessible to the general public. Therefore, obese, meat-eating participants will be randomized to an intervention and control diet: 1) high chlorophyll (green leafy vegetables) and high heme (normal meat) consumption; and 2) habitual high heme, low chlorophyll diet (control). During the intervention periods, all participants will receive individual dietary counseling from a registered dietitian two days per week to reinforce daily consumption goals based on the amounts of chlorophyll and heme in various foods. This study translates preclinical models, utilizes an appropriate at-risk population, and if feasible, has the potential to be tested for efficacy for the reduction of colon cancer risk.

Participants will be recruited through the Auburn University Pharmaceutical Care Clinic and throughout the Auburn community. After completing all baseline procedures, participants will be block randomized by gender due to potential differences in fecal microbiome. All participants will receive the intervention; the order in which it is received will be randomly generated. For the high chlorophyll study arm, a goal of 1 cup cooked dark leafy green vegetables will be prescribed, and participants will be instructed to consume at least ½ cup cooked dark green leafy vegetables during the same meal they consume red meat. The high chlorophyll group will also receive a variety of frozen dark green leafy vegetables, including, spinach, kale, collards, mustard greens, and turnip greens. Frozen vegetables are provided because flash-freezing minimizes nutrient loss and prevents chlorophyll degradation. Though the chlorophyll content varies between these species, it is exponentially higher than other green vegetables in the brassica family. Participants will be instructed to consume cooked vegetables, rather than raw, to increase the bioavailability of chlorophyll and reduce the volume of the needed amount of vegetable.

After each 4-week period, participants will complete questionnaires, return unused frozen vegetables (which will be tracked), provide a stool sample, and undergo phlebotomy. Study staff will obtain two 24-hour dietary recalls on non-consecutive days. Participants will be provided with an additional fecal collection kit for the sample that will be obtained prior to the next dietary arm assignment.

The behavioral framework of this intervention will utilize Social Cognitive Theory as the basis for behavior change in each intervention arm. Participants will increase self-efficacy of dietary adherence by setting goals and logging daily food intake (self-monitoring), which will be assessed in twice weekly counseling sessions with a registered dietitian.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
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
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Colon Cancer Prevention
Intervention  ICMJE
  • Behavioral: High chlorophyll diet - intervention 1st
    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.
    Other Name: High green leafy vegetable diet
  • Behavioral: High chlorophyll diet - control 1st
    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.
    Other Name: High green leafy vegetable diet
Study Arms  ICMJE
  • Experimental: High chlorophyll diet - intervention 1st
    Participants will complete the 4 week intervention, 4 week washout, then 4 week control period (monitor only)
    Intervention: Behavioral: High chlorophyll diet - intervention 1st
  • Experimental: High chlorophyll diet - control 1st
    Participants will complete the 4 week control period (monitor only), 4 week washout, then 4 week intervention
    Intervention: Behavioral: High chlorophyll diet - control 1st
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 10, 2018)
50
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 12, 2018
Actual Primary Completion Date December 12, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Previous diagnosis of colon cancer
  • Use of any of the following in the past 4 weeks: systemic antibiotics, corticosteroids, immunosuppressive agents, commercial probiotics
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03582306
Other Study ID Numbers  ICMJE AU-18-208
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Andrew Fruge, Auburn University
Study Sponsor  ICMJE Auburn University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andrew D Fruge, PhD, RD Auburn University
PRS Account Auburn University
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP