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AzTrials

Colon Cancer PreventionM3GNCT03582306

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

A study testing High chlorophyll diet - intervention 1st in people with Colon Cancer Prevention, run by Auburn University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Colon Cancer Prevention
What is being tested?
High chlorophyll diet - intervention 1st
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteUnited States
Study dates
23 Jul 2018to 12 Dec 2018
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Auburn University

    Auburn, Alabama, 36849

Other trials in United States

About this study

Official title: Exploring the Effects of a High Chlorophyll Dietary Intervention to Reduce Colon Cancer Risk in Adults: The Meat and Three Greens Feasibility Trial

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.

Read the 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.

Being tested
High chlorophyll diet - intervention 1st, High chlorophyll diet - control 1st
Keywords
colon cancer, dietary intervention, vegetables, microbiota
Medical subject headings
Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • High chlorophyll diet - intervention 1stBehavioural

    Also called High green leafy vegetable diet

    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.

  • High chlorophyll diet - control 1stBehavioural

    Also called High green leafy vegetable diet

    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.

Study groups in NCT03582306
Study groupRoleWhat they receive
High chlorophyll diet - intervention 1stExperimentalParticipants will complete the 4 week intervention, 4 week washout, then 4 week control period (monitor only)
Receives: Behavioral: High chlorophyll diet - intervention 1st
High chlorophyll diet - control 1stExperimentalParticipants will complete the 4 week control period (monitor only), 4 week washout, then 4 week intervention
Receives: Behavioral: High chlorophyll diet - control 1st

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Feasibility - accrual

    Accrue 50 participants

    Measured: 9 months

  2. Feasibility - retention

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

    Measured: 12 weeks

  3. Feasibility - adherence

    Meet chlorophyll intake goals 90% of days

    Measured: 4 weeks during intervention phase

Secondary outcomes (8)
  1. DNA damage

    Serum 8-hydroxy-2'-deoxyguanosine

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

  2. Inflammatory marker - C-Reactive Protein

    Serum hsCRP

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

  3. Inflammatory marker - Tumor Necrosis Factor-alpha

    Serum TNF-alpha

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

  4. Inflammatory marker - Interleukin 6

    Serum IL-6

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

  5. Gut microbe composition

    16s changes in microbiota alpha diversity

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

  6. Bile acids

    Plasma primary and secondary bile acids

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

  7. Body composition

    Body fat percentage using Bioelectrical Impedence Analysis

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

  8. Acceptability

    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.

    Measured: 4 weeks during intervention phase

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jul 2018
  2. Study start23 Jul 2018
  3. Primary completion12 Dec 2018
  4. Study completion12 Dec 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Crossover
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)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03582306
Sponsor's protocol ID
AU-18-208
Acronym
M3G
Status last verified
Oct 2019
First submitted
10 Jun 2018
Last updated
15 Oct 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 27988219
  • 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.

    PubMed 30420171
  • 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.

    PubMed 31581743
  • 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.

    PubMed 35413837

Questions about this trial

What is this clinical trial studying?

A study testing High chlorophyll diet - intervention 1st in people with Colon Cancer Prevention, run by Auburn University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Feasibility - accrual (time frame: 9 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03582306, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2019.

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