Effects of a Western-type Diet on Colorectal Inflammation

Study Overview
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Brief Summary
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This study will look at the inflammatory (changes usually associated with infection/injury to the body) and bowel permeability (bowel's ability to allow contents to enter the body) effects of a Western-style diet (high fat and low in calcium) and a prudent-style diet (low fat and high in calcium) on the colon (large bowel). This study may provide information to prevent colorectal cancer in a high-risk population

Detailed Description
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Hypothesis: Compared to a prudent-style diet, does a western-style diet increase colorectal inflammation thereby increasing gut permeability and causing increased endotoxins and markers of systemic inflammation. This is a single blind crossover study. Subjects will be randomized to begin on either a WD or a PD for 30 + 3 days. Once that dietary intervention is complete, subjects will have a four (4) week wash-out period and then will be placed on the other dietary intervention for 30 + 3 days. The following study measures are performed during both the dietary intervention study periods. All the baseline tests will be repeated at the end of each dietary intervention period.

Official Title
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Effects of a Western-type Diet on Colorectal Inflammation, Gut Permeability and Systemic Endotoxemia

Conditions
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Colorectal Inflammation

Intervention / Treatment
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* Dietary Supplement: Western style diet (high fat and low in calcium)
* Dietary Supplement: Prudent-style diet (low fat and high in calcium)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or post-menopausal ( 2 years after menopause or stopping HRT)healthy female subjects Age between 50 and 72 years At increased risk for colorectal cancer (this includes those have had a colorectal adenoma excised, or have a first or second degree relative with colorectal neoplasia). Exclusion Criteria: Personal history of cancer other than non-melanoma skin cancer within the past 10 years History of hereditary non-polyposis colon cancer Intestinal malabsorption, inflammatory bowel disease Prior gastrointestinal surgery other than appendectomy or surgery of the esophagus Any excess bleeding or coagulation disorders Subjects taking anti-coagulants, sterol-binding resins, NSAIDs other than aspirin, < 600mg per day, other study medications, or other multiple medications that might, in the view of the study physicians, alter colonic function or inflammation Total cholesterol greater than 240mg/dl, triglycerides > 600mg, LDL-C > 175 Subjects with a history of coronary artery disease HIV positive subjects Subjects taking antibiotics, anti-diabetes, hormone replacement therapy, oral, transplanted or injected contraceptives (thyroid hormone therapy is permitted as long as the subject is euthyroid) Currently participating in other clinical studies or completed participation in other clinical studies within the last 30 days

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 72 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Western style diet<br>high-fat, low-calcium diet | Dietary Supplement: Western style diet (high fat and low in calcium)<br>* Subjects will be randomized to begin on either a WD or a PD for 30 + 3 days. Once that dietary intervention is complete, subjects will have a four (4) week wash-out period and then will be placed on the other dietary intervention for 30 + 3 days<br>|
| Active Comparator: Prudent diet<br>low-fat, calcium-sufficient diet | Dietary Supplement: Prudent-style diet (low fat and high in calcium)<br>* Subjects will be randomized to begin on either a WD or a PD for 30 + 3 days. Once that dietary intervention is complete, subjects will have a four (4) week wash-out period and then will be placed on the other dietary intervention for 30 + 3 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammation in the rectosigmoid epithelium |  | visit 1, 30 days after the first dietary intervention and 30 days after the second dietary intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circulating endotoxin levels |  | visit 1, 30 days after the first dietary intervention and 30 days after the second dietary intervention | 
| Expression profiles of pro- and anti-inflammatory genes in rectosigmoid biopsies |  | visit 1, 30 days after the first dietary intervention and 30 days after the second dietary intervention | 
| Gut permeability |  | visit 1, 30 days after the first dietary intervention and 30 days after the second dietary intervention | 
| Inflammatory cytokines in the colorectal mucosa and serum |  | visit 1, 30 days after the first dietary intervention and 30 days after the second dietary intervention | 
| Luminal and adherent gut microbiota |  | visit 1, 30 days after the first dietary intervention and 30 days after the second dietary intervention | 
| Fecal calprotectin levels in the stool samples |  | visit 1, 30 days after the first dietary intervention and 30 days after the second dietary intervention |