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
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Dietary Supplement: dietary intervention
Dietary Supplement: folic acid
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase I Clinical Study of Folate

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • •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 ]

Enrollment: 20
Study Start Date: September 2004
Study Completion Date: March 2008
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
Detailed 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.

  Eligibility

Ages Eligible for Study:   40 Years to 72 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00096330

Locations
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Sponsors and Collaborators
Roswell Park Cancer Institute
Investigators
Principal Investigator: James Marshall, PhD Roswell Park Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00096330     History of Changes
Other Study ID Numbers: CDR0000393455, P30CA016056, RUH-PHO-0514-0404, RPCI-EPR-20703, AECM-0401022E, NEMCH-6060
Study First Received: November 9, 2004
Last Updated: January 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Roswell Park Cancer Institute:
colon cancer
rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Folic Acid
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Hematinics
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014