Effects of a Western-type Diet on Colorectal Inflammation

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

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

Study Overview

• Status: Completed
• Conditions: Colorectal Inflammation
• Intervention / Treatment: Dietary supplement: Western style diet (high fat and low in calcium); Dietary supplement: Prudent-style diet (low fat and high in calcium)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Rockefeller University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 72 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Western style diet; high-fat, low-calcium diet	Dietary supplement: Western style diet (high fat and low in calcium); 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
Active Comparator: Prudent diet; low-fat, calcium-sufficient diet	Dietary supplement: Prudent-style diet (low fat and high in calcium); 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Rockefeller University
• Investigators: Principal Investigator: Swaroop Pendyala, MD, Rockefeller University

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: March 19, 2009
• First Submitted That Met QC Criteria: March 19, 2009
• First Posted (Estimate): March 20, 2009

Study Record Updates

• Last Update Posted (Estimate): January 11, 2012
• Last Update Submitted That Met QC Criteria: January 10, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcium; Calcium, Dietary
• Other Study ID Numbers: SWP-0658