Healthy Subject
Conditions
Keywords
Colon, Rectum
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.
Interventions
DIETARY_SUPPLEMENTDietary Fiber
Given fiber supplement
DIETARY_SUPPLEMENTFish Oil
Given fish oil supplement
OTHERComparator
Given fiber supplement placebo
Sponsors
National Cancer Institute (NCI)
Texas A&M University
Fred Hutchinson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred December 2020 thru March 2022 via ads, fliers and social media in the Seattle area. We received 243 screening questionnaires; 88 were incomplete. Of 155 completed, 95 were ineligible (61.3%). We contacted the 60 eligible; 43 attended orientation; 38 signed consent. Three were not randomized (2 ineligible based on abnormal clinical lab tests at baseline and 1 withdrew because of stool collection). Overall, we met planned recruitment goals.
Pre-assignment details
Before randomization to determine the crossover order of supplements (active-washout-comparison, or comparison-washout-active), consented participants had a blood draw. Samples were sent to CLIA-certified Quest Labs for kidney/liver function tests as part of eligibility criteria. Two of the 38 were ineligible based on the lab test criteria. Additionally, 1 person decided they did not want to enter the trial and was not randomized.
Participants by arm
| Arm | Count |
|---|---|
| Cross-over Randomization 1: Fiber Plus Fish Oil Followed by Comparator Participants received a fiber supplement and fish oil supplement PO daily for 30 days. After a washout period, of at least 60 days, they received the comparator supplements (also for 30 days) | 15 |
| Cross-over Randomization 2: Comparator Followed by Fiber Plus Fish Oil Participants received the comparator supplements PO daily for 30 days. After a washout period, of at least 60 days, they received the fiber supplement and fish oil supplement (also for 30 days) | 16 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 5 | 1 |
Baseline characteristics
| Characteristic | Cross-over Randomization 1: Fiber Plus Fish Oil Followed by Comparator | Cross-over Randomization 2: Comparator Followed by Fiber Plus Fish Oil | Total |
|---|---|---|---|
| Age, Continuous | 60.7 years STANDARD_DEVIATION 6.5 | 64.9 years STANDARD_DEVIATION 5.3 | 62.6 years STANDARD_DEVIATION 6.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 15 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 12 Participants | 14 Participants | 26 Participants |
| Sex: Female, Male Female | 12 Participants | 13 Participants | 25 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 16 |
| other Total, other adverse events | 0 / 19 | 0 / 16 |
| serious Total, serious adverse events | 0 / 19 | 0 / 16 |
Outcome results
Primary
Feasibility and Retention for a Trial With Daily Doses of 35 g of Fiber and 6.2 g of EPA +DHA (and Corresponding Comparators)
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.
Time frame: Baseline to completion of the 2 study time periods
Population: All participants who consented and started the intervention.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cross-over Randomization 1: Fiber Plus Fish Oil Followed by Comparator | Feasibility and Retention for a Trial With Daily Doses of 35 g of Fiber and 6.2 g of EPA +DHA (and Corresponding Comparators) | Participants with complete measures (who completed Period 1 and Period 2) | 14 Participants |
| Cross-over Randomization 1: Fiber Plus Fish Oil Followed by Comparator | Feasibility and Retention for a Trial With Daily Doses of 35 g of Fiber and 6.2 g of EPA +DHA (and Corresponding Comparators) | Participants with partial measures (who only completed Period 1) | 1 Participants |
| Cross-over Randomization 1: Fiber Plus Fish Oil Followed by Comparator | Feasibility and Retention for a Trial With Daily Doses of 35 g of Fiber and 6.2 g of EPA +DHA (and Corresponding Comparators) | Participants who dropped out during Period 1 | 4 Participants |
| Cross-over Randomization 1: Fiber Plus Fish Oil Followed by Comparator | Feasibility and Retention for a Trial With Daily Doses of 35 g of Fiber and 6.2 g of EPA +DHA (and Corresponding Comparators) | Participants who dropped out during Period 2 | 0 Participants |
| Cross-over Randomization 2: Comparator Followed by Fiber Plus Fish Oil | Feasibility and Retention for a Trial With Daily Doses of 35 g of Fiber and 6.2 g of EPA +DHA (and Corresponding Comparators) | Participants who dropped out during Period 2 | 0 Participants |
| Cross-over Randomization 2: Comparator Followed by Fiber Plus Fish Oil | Feasibility and Retention for a Trial With Daily Doses of 35 g of Fiber and 6.2 g of EPA +DHA (and Corresponding Comparators) | Participants with complete measures (who completed Period 1 and Period 2) | 15 Participants |
| Cross-over Randomization 2: Comparator Followed by Fiber Plus Fish Oil | Feasibility and Retention for a Trial With Daily Doses of 35 g of Fiber and 6.2 g of EPA +DHA (and Corresponding Comparators) | Participants who dropped out during Period 1 | 0 Participants |
| Cross-over Randomization 2: Comparator Followed by Fiber Plus Fish Oil | Feasibility and Retention for a Trial With Daily Doses of 35 g of Fiber and 6.2 g of EPA +DHA (and Corresponding Comparators) | Participants with partial measures (who only completed Period 1) | 1 Participants |
Secondary
Compliance
Serum Phospholipids - Eicosapentaenoic acid (EPA), concentration
Time frame: Average at the end of each intervention period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cross-over Randomization 1: Fiber Plus Fish Oil Followed by Comparator | Compliance | 43.9 mg/L | Standard Deviation 29.7 |
| Cross-over Randomization 2: Comparator Followed by Fiber Plus Fish Oil | Compliance | 3.6 mg/L | Standard Deviation 3 |
Secondary
Number of Differentially Expressed Exfoliome Genes at p<0.01
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.
Time frame: End of Fiber Plus Fish Oil Supplementation vs end of Comparator
Population: All participants who completed both the Fiber Plus Fish Oil Supplement and the Comparator intervention periods in this crossover study and had stools at the end of each intervention period were included in the analysis. RNA-Seq data from stool for 29 participants were analyzed for differential gene expression comparing the end of each intervention period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cross-over Randomization 1: Fiber Plus Fish Oil Followed by Comparator | Number of Differentially Expressed Exfoliome Genes at p<0.01 | Upregulated | 10 number of genes at p<0.01 |
| Cross-over Randomization 1: Fiber Plus Fish Oil Followed by Comparator | Number of Differentially Expressed Exfoliome Genes at p<0.01 | Downregulated | 2 number of genes at p<0.01 |
| Cross-over Randomization 1: Fiber Plus Fish Oil Followed by Comparator | Number of Differentially Expressed Exfoliome Genes at p<0.01 | Unchanged | 988 number of genes at p<0.01 |