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COffee and Metabolites Modulating the Gut MicrobiomE in Colorectal caNCER (COMMENCER)

Primary Purpose

Colorectal Cancer, Coffee, Gastrointestinal Microbiome

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nestlé NESCAFÉ® TASTER'S CHOICE® House Blend capsule.
Placebo
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Colorectal Cancer focused on measuring Liver fat, Gut microbiome, Colorectal cancer, Coffee, Tumor biopsy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participants must meet the following criteria on screening examination to be eligible to participate in the study: 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. Subjects must be able and willing to follow study procedures and instructions. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study. 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). History of diagnosed conditions that may be worsen by coffee, including arrhythmias, insomnia, tremors, tics, generalized anxiety disorder, bipolar disease, panic attacks, Tourette's, epilepsy or overactive bladder. History of adverse reactions to coffee or intolerance of coffee consumption. Inability or unwillingness to swallow capsules. History of malabsorption or uncontrolled vomiting or diarrhea, or any other disease that could interfere with absorption of oral medications. Any uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that, in the opinion of the investigator, may increase the risks associated with study participation or study treatment, limit compliance with study requirements, or interfere with the interpretation of study results. Pregnant or breastfeeding. The effects of coffee on the developing human fetus are unknown. For this reason, women of child-bearing potential 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 she is participating in this study, she should inform her treating physician immediately. Similarly, lactating women are excluded from this study because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with coffee. Consequently, breastfeeding should be discontinued if the mother is enrolled on the study. Presence of synchronous (at the same time) malignancy for which the patient is currently receiving active treatment. Known positive test for human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection.

Sites / Locations

  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Coffee

Placebo

Arm Description

Participants in the active arm will take 10 capsules of coffee, each of which will contain 600 mg Nestlé NESCAFÉ® TASTER'S CHOICE® House Blend (equivalent daily dose: three cups of coffee). Participants will receive a twelve-week supply of blinded drug capsules in the mail from Johnson Compounding Pharmacy. The anticipated duration of the study is at least 8 weeks and no more than 12 weeks.

Participants in the placebo arm will take 10 capsules of placebo.Each placebo capsule will contain 600 mg of microcrystalline cellulose with flavor and food-coloring substances. Participants will receive a twelve-week supply of blinded drug capsules in the mail from Johnson Compounding Pharmacy. The anticipated duration of the study is at least 8 weeks and no more than 12 weeks.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
January 8, 2023
Last Updated
August 29, 2023
Sponsor
Massachusetts General Hospital
Collaborators
National Institutes of Health (NIH), National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05692024
Brief Title
COffee and Metabolites Modulating the Gut MicrobiomE in Colorectal caNCER
Acronym
COMMENCER
Official Title
COMMENCER: COffee and Metabolites Modulating the Gut MicrobiomE in Colorectal caNCER
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 1, 2023 (Anticipated)
Primary Completion Date
June 1, 2026 (Anticipated)
Study Completion Date
June 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
National Institutes of Health (NIH), National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
This research study is a chemoprevention clinical trial, designed to test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the drug is being studied. The investigators plan to recruit 80 participants. Coffee is a complex mixture of hundreds of bioactive compounds, including caffeine, chlorogenic acids, and other polyphenols. Increasing data suggest the anti-cancer benefit of coffee. Observational data have linked coffee drinking to better survival among patients with colorectal cancer. However, there remains uncertainty surrounding the mode of action. The U.S. Food and Drug Administration (FDA) has not approved coffee as a treatment for any disease. The research study procedures include: Screening for eligibility. Two study visits Proton magnetic resonance spectroscopy. Magnetic resonance imaging Ultrasound elastography. Urine, blood, and stool samples collected. Diet and lifestyle questionnaires Collection of archival tumor biopsy tissue. Treatment: Coffee or placebo administered daily, orally for 8-12 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Coffee, Gastrointestinal Microbiome, Stenosis, Fibrosis, Liver, Ultrasound Elastography, Proton Magnetic Resonance Spectroscopy
Keywords
Liver fat, Gut microbiome, Colorectal cancer, Coffee, Tumor biopsy

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Coffee
Arm Type
Active Comparator
Arm Description
Participants in the active arm will take 10 capsules of coffee, each of which will contain 600 mg Nestlé NESCAFÉ® TASTER'S CHOICE® House Blend (equivalent daily dose: three cups of coffee). Participants will receive a twelve-week supply of blinded drug capsules in the mail from Johnson Compounding Pharmacy. The anticipated duration of the study is at least 8 weeks and no more than 12 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants in the placebo arm will take 10 capsules of placebo.Each placebo capsule will contain 600 mg of microcrystalline cellulose with flavor and food-coloring substances. Participants will receive a twelve-week supply of blinded drug capsules in the mail from Johnson Compounding Pharmacy. The anticipated duration of the study is at least 8 weeks and no more than 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Nestlé NESCAFÉ® TASTER'S CHOICE® House Blend capsule.
Intervention Description
Each coffee capsule will contain 600 mg Nestlé NESCAFÉ® TASTER'S CHOICE® House Blend.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Each placebo capsule will contain 600 mg of microcrystalline cellulose with flavor and food-coloring substances.
Primary Outcome Measure Information:
Title
Change in hepatic fat fraction.
Description
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.
Time Frame
2 years after study completion
Secondary Outcome Measure Information:
Title
Change in liver fibrosis assessment and plasma levels of liver enzymes
Description
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.
Time Frame
2 years after study completion
Other Pre-specified Outcome Measures:
Title
Change in the stool microbiome
Description
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).
Time Frame
2 years after study completion
Title
ctDNA analysis
Description
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.
Time Frame
2 years after study completion
Title
Change in stool metabolomics
Description
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.
Time Frame
2 years after study completion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants must meet the following criteria on screening examination to be eligible to participate in the study: 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. Subjects must be able and willing to follow study procedures and instructions. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study. 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). History of diagnosed conditions that may be worsen by coffee, including arrhythmias, insomnia, tremors, tics, generalized anxiety disorder, bipolar disease, panic attacks, Tourette's, epilepsy or overactive bladder. History of adverse reactions to coffee or intolerance of coffee consumption. Inability or unwillingness to swallow capsules. History of malabsorption or uncontrolled vomiting or diarrhea, or any other disease that could interfere with absorption of oral medications. Any uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that, in the opinion of the investigator, may increase the risks associated with study participation or study treatment, limit compliance with study requirements, or interfere with the interpretation of study results. Pregnant or breastfeeding. The effects of coffee on the developing human fetus are unknown. For this reason, women of child-bearing potential 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 she is participating in this study, she should inform her treating physician immediately. Similarly, lactating women are excluded from this study because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with coffee. Consequently, breastfeeding should be discontinued if the mother is enrolled on the study. Presence of synchronous (at the same time) malignancy for which the patient is currently receiving active treatment. Known positive test for human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mingyang Song, MD, ScD
Phone
(617) 643-3364
Email
msong2@mgh.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Aparna R Parikh, MD, MS
Phone
(617) 726-4000
Email
APARNA.PARIKH@MGH.HARVARD.EDU
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mingyang Song, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mingyang Song, MD
Phone
617-643-4464
Email
msong2@mgh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Mingyang Song, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The results should be made public within 24 months of reaching the end of the study upon review by the MGH Research Pharmacy staff and acknowledgement of the CTP. The end of the study is the time point at which the last data items are to be reported, or after the outcome data are sufficiently mature for analysis, as defined in the section on Sample Size, Accrual Rate and Study Duration. If a report is planned to be published in a peer-reviewed journal, then that initial release may be an abstract that meets the requirements of the International Committee of Medical Journal Editors. A full report of the outcomes should be made public no later than three (3) years after the end of the study.
IPD Sharing Time Frame
Data can be shared no earlier than 1 year following the date of publication
IPD Sharing Access Criteria
Contact the Partners Innovations team at http://www.partners.org/innovation
IPD Sharing URL
http://www.partners.org/innovation

Learn more about this trial

COffee and Metabolites Modulating the Gut MicrobiomE in Colorectal caNCER

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