Effect of High-Legume Diet on Colorectal Cancer Risk

Inflammation Clinical Trial

Official title: The Effects of a High Legume Low Glycemic Index Diet on Insulin Resistance and Inflammation in Patients at High Risk for Colorectal Adenoma Recurrence

Status Completed

Clinical Trial Summary

This study, sponsored by the National Cancer Institute and Penn State University, will examine how a diet high in legumes (dried beans) influences risk factors for colon cancer and polyps. Many scientists believe that colon and rectal cancers develop from polyps (tumors of the lining of the large bowel). This study will test whether a high-legume diet can reduce levels of certain factors (blood insulin, blood glucose, and markers of inflammation such as C-reactive protein) that at elevated levels are known to increase the risk of colorectal polyps and colon cancer.

Healthy men between 35 and 75 years of age may be eligible for this study, conducted at Penn State University in University Park, Pennsylvania. Candidates are screened with blood tests and measurements of height, weight, and blood pressure. All candidates must have had a colonoscopy within 2 years of entering the study. They may or may not have had adenomas and may or may not be insulin-resistant. Candidates must not have cancer, heart disease, kidney disease, diabetes, or other serious medical condition, and they must have no history of colorectal cancer, polyp removal, bowel surgery, polyposis syndrome, or inflammatory bowel disease. Participants undergo the following tests and procedures:

• Caloric requirement testing: The subject's resting metabolic rate is measured while fasting and in the early morning at rest to determine daily calorie requirement before beginning the study diet. A special clear plastic hood is placed over the subject's head while his breathing is measured. He can communicate with the technician at all times during the 30-minute test.

• Study diet: Subjects follow two required 4-week diets with a 3-week break in between, followed by an optional third 4-week diet. Subjects eat a healthy American diet for both of the required 4-week diet periods; about 1-1/2 cups of cooked legumes, such as pinto, baked, and navy beans are added to one of the two required diets. For the third (optional) diet period, subjects are given the same 1-1/2 cups of legumes, but are allowed to lose weight. Participants are given packages with all of the food they are to consume during the three diet periods. They may add up to five caffeine-containing beverages per day and up to two alcoholic drinks per week. They must eat all of the food they are given and only the food they are given. Subjects are expected to maintain a constant body weight during the two 4-week required diets, and their caloric intake may be increased or decreased as needed to maintain their screening weight.

• Weight measurements: Subjects are weighed regularly at the clinic.

• Blood samples: Subjects have blood samples drawn at the mid-point of each of the two required 4-week diets and at the beginning and end of each of the three 4-week diets.

• Urine and stool samples: Urine and stool samples are collected at the beginning and end of the two required 4-week diets.

Clinical Trial Description

Clinical, epidemiological, and molecular studies provide compelling evidence that most colorectal cancers arise from adenomas. The epidemiology of adenomas closely resembles that of colorectal cancer itself, and prevention of adenomas will most likely prevent colorectal cancer. Insulin resistance and type 2 diabetes are emerging as significant risk factors for colorectal (CRC) cancer and adenomas. Insulin resistance is defined as impaired biological response to the action of insulin. It is characterized by compensatory hyperinsulinemia and is associated with increased risk for Type 2 diabetes. C-peptide, a marker of insulin production, is elevated in IR and is also a risk factor for CRC. Both insulin resistance and colorectal cancer are increasingly recognized as chronic, low-level, inflammatory states. C-reactive protein (CRP), an acute phase protein and a sensitive marker of sub-clinical inflammation, is a risk factor for both IR and CRC.

Analysis from the Polyp Prevention Trial (PPT), a multi-center, randomized trial of 1905 participants who had a colorectal adenoma, showed that legume consumption was significantly associated with reduction of both adenoma recurrence and advanced adenoma recurrence. Legumes are a rich source of dietary fibers and anti-inflammatory, anti-cancer phytochemicals.

We are evaluating the effects of a legume enriched, low glycemic index, high fermentable fiber diet, on CRP, (a measure of inflammation) and C-peptide (a measure of insulin resistance) in participants with four possible combinations of the risk factors insulin resistance and history of adenomatous polyps. In a randomized crossover design controlled feeding study each participant consumed the above experimental diet and a control diet for four weeks with a two week washout period between diets. 65 male participants were recruited and randomized into four groups. A secondary objective is to assess whether these endpoints change by IR status or a history of adenomas. In addition, potential fecal markers of CRC risk are being measured to assess changes in gastrointestinal inflammation, including mRNA from exfoliated fecal colonocytes. To our knowledge this is the first controlled feeding study: 1. to examine the effects of legumes or a low GI diet on markers of inflammation; 2. to compare the effects of a dietary intervention on patients with a history of colon adenomas with or without IR; and 3. to measure the effects of dietary changes in human intestinal gene expression profiles using exfoliated colonocytes. ;

Related Conditions & MeSH terms

• Colonic Neoplasms
• Diet
• Inflammation
• Insulin
• Prevention and Control

• NCT number: NCT00339469
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Early Phase 1
• Start date: August 3, 2005
• Completion date: February 13, 2018