Effect of High-Legume Diet on Colorectal Cancer Risk
| Status: | Completed |
|---|---|
| Conditions: | Colorectal Cancer, Endocrine |
| Therapuetic Areas: | Endocrinology, Oncology |
| Healthy: | No |
| Age Range: | 35 - 75 |
| Updated: | 4/6/2019 |
| Start Date: | August 3, 2005 |
| End Date: | February 13, 2018 |
The Effects of a High Legume Low Glycemic Index Diet on Insulin Resistance and Inflammation in Patients at High Risk for Colorectal Adenoma Recurrence
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.
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, 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.
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.
- INCLUSION CRITERIA
1. Subjects are between 35-75 years old.
2. Subjects are male.
3. Subjects have a BMI 25.0-34.9 kg/m(2)
Group 1 (adenoma, IR)
4. Subjects had a colonoscopy within the last two years
5. Subjects who had had one or more histologically confirmed adenomas removed from
the colon during a colonoscopy in the last two years, in which the cecum was
visualized, all polyps were removed, and the bowel was adequately prepared.
6. Subjects have had either an adenoma previous to the above colonoscopy or multiple
adenomas during the above colonoscopy.
7. Subjects should have more than one previous adenoma in the colon. Rectal adenomas
will be excluded. (If a person has only rectal adenomas or 1 colon and numerous
rectal adenomas they will be excluded from the study, since the epidemiology for
rectal and colon adenomas differ)
8. Subjects are insulin resistance as determined by the Homeostasis Assessment Model
(HOMA-IR), a mathematical model which allows values for insulin sensitivity and
beta-cell function (expressed as percent of normal) to be obtained from
simultaneous fasting plasma glucose and fasting insulin. HOMA-IRA is calculated
by fasting serum insulin (FI in uU/mL); fasting glucose (FG in mmol/L) / 22.5 or
HOMA-IR = FIxFG/22.5 (188). Values greater than or equal to 2.61 are considered
insulin resistant
Group 2 (adenomas, non IR)
9. Subjects had a colonoscopy within the last two years.
10. Subjects had one or more histologically confirmed colorectal adenomas removed
during a colonoscopy in the last two years in which the cecum was visualized, all
polyps were removed, and the bowel was adequately prepared.
11. Subjects have had either an adenoma previous to the above colonoscopy or multiple
adenomas during the above colonoscopy.
12. Subjects should have more than 1 adenoma in the colon (vs rectum).
13. Subjects are not insulin resistance as determined by HOMA-IR.
Group 3 (no adenoma, IR)
14. Subjects (controls) had a colonoscopy within the last two years and who had no
histologically confirmed colorectal adenomas during the colonoscopy, in which the
cecum was visualized and the bowel was adequately prepared.
15. Subjects have had no previous adenoma.
16. Subjects are insulin resistant as determine by HOMA-IR.
Group 4 (no adenoma, non IR)
17. Subjects (controls) had a colonoscopy within the last two years and had no
histologically confirmed colorectal adenomas during the colonoscopy, in which the
cecum was visualized and the bowel was adequately prepared.
18. Subjects have had no previous adenomas.
19. Subjects are not insulin resistance as determined by HOMA-IR.
EXCLUSION CRITERIA
All Subjects
1. A serious medical condition such as cancer, heart disease, kidney disease, diabetes or
other serious medical condition.
2. A history of colorectal cancer, surgical resection of adenomas, bowel resection, the
polyposis syndrome, or inflammatory bowel disease.
3. Smoked regularly in the past year.
4. Have a medical condition or dietary restrictions or practices that would substantially
limit compliance with the dietary protocol.
5. Planning on changing diet, exercise or other health behavior in the next 6 months.
6. Taking any medication that may alter inflammation markers, insulin, glucose, and
lipids.
Potential participants should not be regularly using the following preparations:
- Antibiotics
- Non-steroidal anti-inflammatory drugs (aspirin and other non-aspirin NSAIDS like
inbuprofen, naproxen, indomethacin, piroxicam, COX-2-specific inhibitor drugs such as
celecoxib, etodolac, and meloxicam)
- Glucocorticoids and other steroids
- Oral glucose preparations (e.g. Actos, Amaryl, Avandia, DiaBeta, Diabinese, Dymelor,
Glucophage(XR), Glucotrol(XL), Glucovance, Glynase Pres Tab, Glyset, Micronase,
Orinase, Prandin, Precose, Starlix, Tolinase)
- Insulin injections
- Statins (e.g. atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin,
simvastatin)
- Bile Acid Resins (e.g. cholestyramine, colestipol, colesevelam)
- Nicotinic Acid (Niacin)
- Fibrates (e.g. clofibrate, fenofibrate, gemfibrozil)
- Combination Lipid Lowering Drugs (e.g. Crestor)
Participants will be asked not to use any supplements (including herbal and alternative
therapies) other than a regular multi-vitamin/mineral while participating in the study.
While we ask subjects to stop use of OTC medications during the study, we recognize that
there may be occasional use of OTC analgesics during the course of the study. At least
under some circumstances we will permit the use of OTC analgesics, which is otherwise
listed as an exclusion criteria. At their scheduled blood draws, we will ask subjects to
report any use of OTC medications during the past week. Participants will also be asked to
limit their use of alcohol during the study to less than or equal to 2 drinks/week.
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