Folate-Depleted Diet Compared With Folate-Supplemented Diet in Preventing Colorectal Cancer in Patients at High Risk for Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention therapy is the use of certain agents to try to prevent the development of cancer. The use of folic acid may be effective in preventing colorectal cancer. Eating a diet rich in folic acid may prevent the development of colorectal cancer. PURPOSE: This randomized phase I trial is studying how well a folate-depleted diet works compared to a folate-supplemented diet in preventing colorectal cancer in patients who are at high risk for developing colorectal cancer.

Detailed Description
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OBJECTIVES: Primary Analyze the effects of a folate-depleted vs a folate-supplemented diet on folate-related DNA endpoints (e.g., genomic and gene-specific DNA methylation and DNA strand breaks) in rectal epithelial cells in patients at high risk for colorectal neoplasia. Analyze the effects of these dietary interventions on folate-related DNA endpoints (e.g., genomic and gene-specific DNA methylation, DNA strand breaks, and uracil incorporation into DNA) in blood mononuclear cells in these patients. Secondary Analyze the effects of these dietary interventions on the patterns of differential gene expression in rectal epithelial cells and blood mononuclear cells in these patients. OUTLINE: This is a randomized, single-blind study. Run-in period: Patients are placed on an average folate-containing diet for 56 days. Randomization: After completion of the run-in period, patients are randomized to 1 of 2 arms. Arm I (folate depleted diet): Patients are placed on a low-folate diet for 84 days. Patients receive oral folic acid supplementation once daily on days 57-84. Arm II (folate supplemented diet): Patients continue on an average folate-containing diet for an additional 56 days. Patients receive oral folic acid supplementation once daily on days 1-56. Patients are followed at 4 weeks. PROJECTED ACCRUAL: A total of 20 patients (10 per arm) will be accrued for this study within 2.5 years.

Official Title
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Phase I Clinical Study of Folate

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Dietary Supplement: dietary intervention
* Dietary Supplement: folic acid


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Healthy persons at increased risk for colorectal neoplasia due to 1 of the following reasons: Personal history of colorectal adenomatous polyps Family history of colorectal adenoma or adenocarcinoma No history of multiple family members with colorectal neoplasia that is suggestive of dominant hereditary neoplasia PATIENT CHARACTERISTICS: Age 40 to 72 Performance status Ambulatory Life expectancy At least 6 months Hematopoietic No excessive bleeding or coagulation disorder Hepatic ALT or AST ≤ 2 times upper limit of normal No unexplained elevated alkaline phosphatase Renal Creatinine ≤ 2.0 mg/dL Cardiovascular Homocysteine concentration ≤ 17um/L No sustained blood pressure > 150/95 mm Hg for 3 consecutive readings Other Vitamin B_12 ≥ 250 pg/mL Folate level ≤ 20 mg/dL HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 4 weeks after study participation No intestinal malabsorption or inflammatory bowel disease No prior malignancy except nonmelanoma skin cancer No calcium metabolism abnormalities or predisposing conditions, such as hyperparathyroidism No untreated hyperthyroidism No untreated insulin-requiring diabetes mellitus No daily alcohol intake > 2 ½ shot glasses of whiskey or three 8 ounce glasses of beer or wine No other serious illness that might limit life expectancy to < 6 months PRIOR CONCURRENT THERAPY: Biologic therapy None Chemotherapy None Endocrine therapy No concurrent hormone replacement therapy, including oral, transplanted, or injected contraceptives Concurrent thyroid hormone replacement is allowed as long as the patient is euthyroid for 3 months Radiotherapy None Surgery No prior gastrointestinal surgery, including gastrectomy or small or large bowel resections Prior appendectomy or surgery of the esophagus allowed Other More than 3 months since regular ingestion of ≥ 650 mg per day of aspirin (≥ 2 tablets of 325 mg regular strength OR > 1 tablet of 500 mg extra strength aspirin) More than 3 months since regular daily ingestion of nonsteroidal anti-inflammatory drugs At least 1 month since vitamin, mineral, or herbal supplementation No other concurrent vitamin, mineral, or herbal supplementation No concurrent anticoagulants No concurrent sterol-binding resins (i.e., cholestyramine) No other concurrent investigational drugs or medications that might alter rectal mucosal proliferation, folate metabolism, or renal/hepatic impairment No concurrent weight control medications No concurrent supplemental folate preparations containing > 400 mcg of folic acid per day No concurrent lipid-lowering medications The following concurrent statin drugs are allowed provided patient has been taking a stable dose for ≥ 1 month: Atorvastatin 10 or 20 mg/day Fluvastatin 20 or 40 mg/day Lovastatin 10 or 20 mg/day Pravastatin 10 or 20 mg/day Simvastatin 5 or 10 mg/day

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 72 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Dietary Supplement: dietary intervention|oral folic acid supplementation once daily on days 57-84|
|Dietary Supplement: folic acid|oral folic acid supplementation once daily on days 1-56.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| •Analyze the effects of a folate-depleted vs a folate-supplemented diet on folate-related DNA endpoints |  | pre and post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colon cancer, rectal cancer