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

Roswell Park Comprehensive Cancer Center

Status and phase

Completed

Phase 1

Conditions

Colorectal Cancer

Treatments

Dietary Supplement: folic acid

Dietary Supplement: dietary intervention

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00096330

CDR0000393455

P30CA016056 (U.S. NIH Grant/Contract)

RPCI-EPR-20703

AECM-0401022E

NEMCH-6060

RUH-PHO-0514-0404

Details and patient eligibility

About

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.

Full description

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.

Enrollment

20 patients

Sex

All

Ages

40 to 72 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

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