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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT00096330
First received: November 9, 2004
Last updated: January 10, 2014
Last verified: January 2014

November 9, 2004
January 10, 2014
September 2004
February 2007   (final data collection date for primary outcome measure)
•Analyze the effects of a folate-depleted vs a folate-supplemented diet on folate-related DNA endpoints [ Time Frame: pre and post treatment ] [ Designated as safety issue: No ]
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Complete list of historical versions of study NCT00096330 on ClinicalTrials.gov Archive Site
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Folate-Depleted Diet Compared With Folate-Supplemented Diet in Preventing Colorectal Cancer in Patients at High Risk for Colorectal Cancer
Phase I Clinical Study of Folate

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.

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.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Colorectal Cancer
  • 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.
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
March 2008
February 2007   (final data collection date for primary outcome measure)

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
Both
40 Years to 72 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00096330
CDR0000393455, P30CA016056, RUH-PHO-0514-0404, RPCI-EPR-20703, AECM-0401022E, NEMCH-6060
Yes
Roswell Park Cancer Institute
Roswell Park Cancer Institute
National Cancer Institute (NCI)
Principal Investigator: James Marshall, PhD Roswell Park Cancer Institute
Roswell Park Cancer Institute
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP