This is research study is assessing the effects of 6-g daily use of freeze-dried instant coffee on liver fat and fibrosis and the gut microbiome and metabolome in patients who have completed routine treatment (including surgery, chemotherapy and radiotherapy) for stage I-III colorectal cancer.
Participants must have histologically confirmed stage I, II, or III colon or rectal adenocarcinoma and have completed standard treatment (including surgery, chemotherapy and radiotherapy) at least 2 months ago.
Age 18 years or older.
This study will only include adult participants because colorectal carcinogenesis in children is more likely to be related to a cancer predisposition syndrome with distinct biological mechanisms compared with sporadic colorectal cancer in adults.
The effects of coffee on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Participants who are receiving any other investigational agents.
Concurrent use of other anti-cancer therapy, including chemotherapy agents, targeted agents, biological agents, immunotherapy, or investigational agents not otherwise specified in this protocol.
Regularly consuming more than 2 cups of coffee ( 8 oz) per day for at least 3 days a week in the past month.
Current or recent use (within 1 month) of any coffee supplements (e.g., green coffee extracts).
Parallel
Nestlé NESCAFÉ® TASTER'S CHOICE® House Blend capsule.
DrugEach coffee capsule will contain 400 mg Nestlé NESCAFÉ® TASTER'S CHOICE® House Blend.
Placebo
DrugEach placebo capsule will contain 400 mg of microcrystalline cellulose with flavor and food-coloring substances.
Change in hepatic fat fraction.
This will be assessed by proton magnetic resonance spectroscopy (1H-MRS) at randomization and the end of the intervention: The investigators will assess the treatment effect using linear mixed effects model that includes time, group assignment, and the group-by-time interaction as the primary independent variables.
Change in liver fibrosis assessment and plasma levels of liver enzymes
This will be analyzed including the score assessed by the FibroScan® system, plasma liver enzymes, and fibrosis-4 index, at randomization and the end of the intervention: The investigators will assess the treatment effect using linear mixed effects model that includes time, group assignment, and the group-by-time interaction as the primary independent variables.
Change in the stool microbiome
Stool microbiome will be assessed by shotgun metagenome sequencing at randomization and the end of the intervention. The investigators will use the established computational tools developed by Dr. Huttenhower (http://huttenhower.sph.harvard.edu/biobakery) for the analysis, including LEfSe (Linear Discriminant Analysis Effect Size) and MaAsLin2 (Multivariate Analysis by Linear models).
ctDNA analysis
ctDNA (binary; positive vs. negative) will be assessed after intervention according to methods appropriate for this exploratory analysis. The investigators will conduct an exploratory analysis with ctDNA to understand if effects are mediated through reducing circulating tumor cells. Tissue and post-treatment blood specimens will be prepared and sent to Natera Inc® for ctDNA assessment.
Change in stool metabolomics
Stool metabolomics will be assessed at randomization and the end of the intervention: The treatment effect on metabolites (log-transformed whenever needed) will be assessed by linear mixed effects model that includes time, group assignment, and the group-by-time interaction as the primary predictors.
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Massachusetts General Hospital
Lead sponsor
National Institutes of Health (NIH)
Collaborator
National Cancer Institute (NCI)
Collaborator
