PRevention Using EPA Against coloREctal Cancer

Colorectal Adenoma Clinical Trial

— PREPARE  

Official title:

PREPARE: PRevention Using EPA Against coloREctal Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04172636
• Other study ID #: To be assigned
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 1, 2020
• Est. completion date: October 31, 2022

Study information

• Verified date: February 2020
• Source: Harvard Medical School
• Contact: Mingyang Song, MD, ScD
• Phone: 6174321301
• Email: mis911[@]mail.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Within the gastroenterology practice of Massachusetts General Hospital (MGH), the investigators will conduct a prospective, single-arm clinical trial to measure the effects of daily 4-gram eicosapentaenoic acid (EPA), through treatment with AMR101 (VASCEPA, icosapent ethyl) on stool and tissue biomarkers associated with colorectal cancer.

Description:

This study will investigate the effects of standard-dose EPA treatment using the FDA-approved drug AMR101. AMR101 (icosapent ethyl) is a prescription medicine for adults to lower blood levels of triglycerides. It is supplied as a liquid-filled gel capsule for oral administration. The standard dose is 4 g per day (administered as 4 one-gram capsules). Each 1-gram capsule of AMR101 contains 1 gram of icosapent ethyl, which is an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA).

EPA possesses triglyceride-lowering and anti-inflammatory activities, and has been suggested to be beneficial for a variety of health outcomes in adults, including coronary heart disease, stroke, type 2 diabetes,depression, and inflammatory bowel disease, although the data are not univocal. Increasing evidence supports the anticancer effect of EPA.

Colorectal cancer is the third leading cause of cancer-related deaths in the US. Substantial data support the benefit of EPA for colorectal cancer prevention and treatment, which may be mainly due to the immunomodulatory and anti-inflammatory activity of EPA. Increasing data support that gut microbes are pivotal in integrating dietary cues with host immunity, and that disturbances in the gut microbiota may promote colorectal cancer by breakdown of intestinal immune homeostasis. Dietary fat composition is a major driver of the gut microbial community structure and EPA has been shown to enrich the gut bacteria that possess immunoprotective activities. These data together the investigator's hypothesis that EPA modulates the gut microbiota to preserve colorectalic immune homeostasis and suppress colorectal cancer. In the current study, the investigators propose to experimentally test this hypothesis by assessing the effect of EPA supplement on the gut microbiota - host immune interaction.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: October 31, 2022
• Est. primary completion date: October 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Participants must meet the following criteria on screening examination to be eligible to participate in the study:

• Underwent screening or surveillance colonoscopy with removal of at least one adenoma within the past 9 months;

• Age 18-80 years.

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. Patients over age 80 will not be enrolled since the benefits and risks of a daily aspirin regimen over the age of 80 have not yet been well-characterized.

• ECOG performance status =2 (Karnofsky =60%, see Appendix A)

• The effects of AMR101 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.

• 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:

• Currently using or have used any fish oil supplement at any dose more than once per week within the last month.

• Regularly consuming more than three servings of fish per week.

• History of allergic reactions attributed to fish or compounds of similar chemical or biologic composition to omega-3 fatty acid.

• Diagnosis of inflammatory bowel disease, liver or kidney disease, bleeding diathesis

• Any prior diagnosis of gastrointestinal cancer (including esophageal, small intestine, colon, pancreatic), or any diagnosis of other cancers (with the exception of non-melanoma skin) in which there has been any active treatment within the last three years.

• Known diagnosis of Familial Adenomatous Polyposis (FAP) or Hereditary Non-Polyposis Colorectal Cancer (HNPCC, Lynch Syndrome).

• Any adenoma that was not completely removed during previous colonoscopy.

• Known bleeding tendency/condition (e.g. von Willebrand disease) or history of peptic ulcer or gastrointestinal bleed, endoscopic complications, or contraindication to colonoscopy.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Inability or unwillingness to abstain from non-protocol use of fish oil supplements or to provide blood or stool samples or colon biopsies during the study.

• Participants who are receiving any other investigational agents.

• Inability or unwillingness to swallow pills.

• Pregnant or breastfeeding.

The effects of AMR101 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 AMR101. Consequently, breastfeeding should be discontinued if the mother is enrolled on the study.

• Known positive test for human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection.

Participants with these infections are ineligible because they are at increased risk of significant complications in the perioperative period, and because fresh tissue from patients with these infections cannot be harvested for research purposes, per institutional policy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.

Related Conditions & MeSH terms

• Adenoma
• Colorectal Adenoma

Intervention

Drug:
• AMR101 (VASCEPA, icosapent ethyl)
Oral administration, 4 grams per day

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Harvard Medical School	Harvard School of Public Health

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The change in stool metabolomics between pre- and post- AMR101 treatment period.	Non-targeted global metabolomics and lipidomics analysis on pre- and post-treatment stool samples will be performed to examine the changes in the stool metabolite profile as a result of the AMR101 treatment. We will focus on short-chain fatty acid and hydroxyl fatty acid.	2 years after study completion
Other	The change in gene expression profile of colorectal tissue between pre- and post- AMR101 treatment period.	RNA-seq analysis to profile gene expression in the mucosal tissue collected before and after AMR101 treatment will be performed to examine whether the AMR101 treatment reduces the gene expression of inflammatory cytokines, chemokines (e.g., TNFa, IL6 and CCL2), and immunosuppressive factors.	2 years after study completion
Primary	The change in the marine omega-3 polyunsaturated fatty acid (MO3PUFA) composition in colorectal tissues as a result of the AMR101 treatment for at least 28 days.	The effect of daily 4-gram AMR101 treatment on MO3PUFA composition in colorectal tissue will be measured through the extraction of fatty acid with gas chromatography-mass spectrometry from the biopsy tissue.	2 years after study completion
Secondary	The change in the gut microbiome composition and function between pre- and post- AMR101 treatment period.	Metagenomic and metatranscriptomic sequencing of microbial DNA and RNA on pre- and post-treatment stool samples will be performed to examine changes in the gut microbial composition and function after AMR101 treatment. We will focus on four microbe classes, including Lactobacillus, Bifidobacterium, Fusobacterium nucleatum, and Escherichia coli.	2 years after study completion