Fiber and Fish Oil Supplements for the Prevention of Colorectal Cancer

Not Applicable

Completed

Conditions: Healthy Subject

Interventions: Dietary Supplement: Dietary Fiber
Dietary Supplement: Fish Oil
Other: Comparator

Registration Number: NCT04211766

Lead Sponsor: Fred Hutchinson Cancer Center

Brief Summary: This trial studies how fiber and fish oil supplements affect the metabolism and activities of colon cells in healthy individuals. Diet is an important risk factor for colorectal cancer, and several dietary components important in colorectal cancer prevention are modified by gut microbial metabolism. Giving fiber and fish oil supplements may inhibit the growth of gut cells and ultimately reduce risk of colorectal cancer.

Detailed Description: Participants are randomized to receive two dietary interventions in assigned random order. They either receive the dietary fiber supplement and fish oil supplement orally (PO) daily or they receive a fiber control and corn oil supplement daily for 30 days during the first intervention period. Then they enter a washout period for 60 days when they do not receive any treatment. After that they complete the second intervention period during which they receive the other intervention.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 38

Inclusion Criteria

Healthy
Normal-overweight (body mass index [BMI] of 18-30 kg/m^2)
Women will be postmenopausal, with no menstrual period in 12 months
Non-smoking
Consume fiber intakes of less than < 20 g/d
White blood cell count 3,000-11,000/mm^3
Platelet count 100,000-400,000 mm^3
Hematocrit 33-50% (women); 36-50% (men)
Bilirubin 0.2-1.3 mg/dL
Aspartate aminotransferase (AST) 0-35 U/L
Alanine aminotransferase (ALT) 0-40 U/L
Alkaline phosphatase 20-125 U/L
Creatinine =< 1.2 mg/dL
Potassium 3.5-5.0 mmol/L

Exclusion Criteria

Chronic medical illness, history of gastrointestinal disorders (e.g., ulcerative colitis, Crohn disease, celiac sprue, hereditary nonpolyposis colorectal cancer [HNPCC], familial adenomatous polyposis, pancreatic disease, previous gastrointestinal resection, radiation or chemotherapy, and cancer (other than non-melanoma skin cancer)
Weight change greater than 4.5 kg within past year
Oral or intravenous (IV) antibiotic use within the past 3 months
Regular use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs)
Smoking or use of cannabis products
Known allergy to fish
Intention to relocate out of study area within next 4 months

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Cross-over Randomization 1: Fiber plus Fish Oil followed by Comparator	Fish Oil	Participants first received a fiber supplement and a fish oil supplement PO daily for 30 days (Period 1). Participants entered a washout period for at least 60 days. For period 2 they received similarly packaged comparator (maltodextrin and corn oil)
Cross-over Randomization 1: Fiber plus Fish Oil followed by Comparator	Comparator	Participants first received a fiber supplement and a fish oil supplement PO daily for 30 days (Period 1). Participants entered a washout period for at least 60 days. For period 2 they received similarly packaged comparator (maltodextrin and corn oil)
Cross-over Randomization 1: Fiber plus Fish Oil followed by Comparator	Dietary Fiber	Participants first received a fiber supplement and a fish oil supplement PO daily for 30 days (Period 1). Participants entered a washout period for at least 60 days. For period 2 they received similarly packaged comparator (maltodextrin and corn oil)
Cross-over Randomization 2: Comparator followed by Fiber plus Fish Oil	Dietary Fiber	Participants first received the comparator (maltodextrin and corn oil) supplement PO daily for 30 days (Period 1). Participants enter a washout period for at least 60 days. For period 2 they received the fiber supplement and a fish oil supplement
Cross-over Randomization 2: Comparator followed by Fiber plus Fish Oil	Fish Oil	Participants first received the comparator (maltodextrin and corn oil) supplement PO daily for 30 days (Period 1). Participants enter a washout period for at least 60 days. For period 2 they received the fiber supplement and a fish oil supplement
Cross-over Randomization 2: Comparator followed by Fiber plus Fish Oil	Comparator	Participants first received the comparator (maltodextrin and corn oil) supplement PO daily for 30 days (Period 1). Participants enter a washout period for at least 60 days. For period 2 they received the fiber supplement and a fish oil supplement

Primary Outcome Measures

Name	Time	Method
Feasibility and Retention for a Trial With Daily Doses of 35 g of Fiber and 6.2 g of EPA +DHA (and Corresponding Comparators)	Baseline to completion of the 2 study time periods	This grant is an R21 with the intent to provide preliminary data to propose a trial with a larger sample size and adequate statistical power.

Secondary Outcome Measures

Name	Time	Method
Number of Differentially Expressed Exfoliome Genes at p<0.01	End of Fiber Plus Fish Oil Supplementation vs end of Comparator	Poly A+ RNA was isolated from exfoliated cells in stool, and libraries generated from stool RNA and sequenced on an Illumina HiSeq 2500 platform. Intestinal exfoliome gene sequencing data from the end of each intervention period were analyzed using differential expression (DE) analysis. Count data were aligned, and sample libraries were filtered and normalized; 25,118 detected features were filtered to keep any feature with \>20 cpm in 73% of samples in at least one of the groups; this resulted in 1000 genes. DE analysis between Fiber Plus Fish Oil Supplement vs the Comparator at the end time point was performed using edgeR with a paired design (Robinson et al, Bioinformatics 2010;26:139). Data are presented as number of DE genes significant at p \< 0.01 (without multiple test correction). Upregulated genes indicate higher gene expression with Fiber Plus Fish Oil vs the Comparator and downregulated genes indicate lower gene expression with Fiber Plus Fish Oil vs the Comparator.
Compliance	Average at the end of each intervention period	Serum Phospholipids - Eicosapentaenoic acid (EPA), concentration