Effect of Folate on DNA in Colon Tissue and Blood Samples From Patients at Increased Risk of Developing Colorectal Neoplasia

NCT00611000 | Completed Phase 1

• 2 other identifiers: CDR0000582113RUH-PHO-0514-0306
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

RATIONALE: Studying samples of blood and tissue from patients at risk of cancer in the laboratory may help doctors learn more about the effect of folate on DNA and identify biomarkers related to cancer. PURPOSE: This phase I trial is studying the effect of folate on DNA in colon tissue and peripheral blood samples from patients at increased risk of developing colorectal neoplasia.

Conditions

Colorectal Cancer

Keywords

colon cancer; rectal cancer

Outcome Measures

Primary Outcomes (3)

• DNA uracil incorporation in peripheral blood mononuclear cells (PBMCs)

• Strand breaks in the coding region of p53 in PBMCs and rectal biopsy cells

• DNA methylation (overall, p53 coding, p16 promoter, MLH1 promoter) in PBMCs and rectal biopsy cells

Secondary Outcomes (1)

• Differential gene expression in colonic and PBMCs by microarray analysis

Interventions

folic acid DIETARY_SUPPLEMENT

DNA methylation analysis GENETIC

gene expression analysis GENETIC

microarray analysis GENETIC

polymorphism analysis GENETIC

laboratory biomarker analysis OTHER

Eligibility Criteria

• Age: 40 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * At increased risk for developing colorectal neoplasia due to 1 of the following: * Personal history of colorectal adenomatous polyps * Family history of colorectal adenoma or adenocarcinoma * No hereditary nonpolyposis colorectal cancer (HNPCC) * No more than one first-degree family member with colorectal or endometrial malignancies PATIENT CHARACTERISTICS: * Ambulatory * Female patients must be ≥ 2 years post-menopausal (i.e., 2 years after the last menstrual period) * Negative pregnancy test * Male patients must use effective contraception during and for 2 months after completion of study treatment (for male patients enrolled in the folate depletion group) * Serum folate level ≤ 20 ng/mL * Plasma vitamin B12 level ≥ 250 pg/mL * Serum homocysteine level ≤ 17 μmol/L * ALT or AST ≤ 2 times upper limit of normal * No unexplained elevated alkaline phosphatase * Creatinine ≤ 2.0 mg/dL * HIV negative * No folate metabolism abnormalities or predisposing conditions * No prior malignancy except nonmelanoma skin cancer * No intestinal malabsorption or inflammatory bowel disease * No excessive bleeding or coagulation disorder * No untreated hyperthyroidism * No diabetes mellitus requiring insulin * No daily alcohol intake \> 2 ½ shot glasses of whisky or three 8-ounce glasses of beer or wine * No sustained blood pressure \> 150/95 mm Hg for three consecutive readings * No other serious illness that would limit life expectancy to \< 6 months PRIOR CONCURRENT THERAPY: * No prior gastrointestinal surgery, including gastrectomy or small or large bowel resections * Prior appendectomy or surgery of the esophagus allowed * More than 3 months since regular ingestion of ≥ 650 mg of aspirin (≥ 2 tablets of 325 mg regular strength OR \> 1 tablet of 500 mg extra strength aspirin) per day * The following drugs are allowed for cardiovascular prophylaxis provided the patient has been taking the drug regularly for ≥ 1 month and continues to take the same dose during study participation: * One or two regular strength aspirin tablets (i.e., 325 mg per tablet) per day * One baby aspirin tablet (81 mg tablet) per day * More than 3 months since regular daily ingestion of other non-steroidal anti-inflammatory drugs (NSAIDs) * No concurrent anticoagulation therapy * No concurrent sterol-binding resins, such as cholestyramine (for the treatment of high blood cholesterol) * No other concurrent investigational drugs * No other concurrent medications that might, in the view of the study physicians, alter rectal mucosal proliferation, folate metabolism, or renal/hepatic metabolism * No concurrent weight control medications * No concurrent supplemental folate preparation containing \> 400 mcg of folic acid per day * No concurrent hormone replacement therapy, including oral, transplanted, or injected contraceptives * Concurrent thyroid hormone replacement allowed provided the patient is euthyroid * No concurrent medication interfering with folic acid metabolic effects, including any of the following: * Methotrexate * Phenytoin * Phenobarbital * Primidone * Sulfonamides * Folinic acid derivatives * No concurrent lipid-lowering medications other than usual doses of the class of drugs known as statins * The following statin drugs are allowed provided the patient has been taking the drug regularly for ≥ 1 month and continues to take the same dose during study participation: * Atorvastatin (10 or 20 mg/day) * Fluvastatin (20 mg or 40 mg/day) * Lovastatin (10 or 20 mg/day) * Pravastatin (10 or 20 mg/day) * Simvastatin (5 or 10 mg/day)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Rockefeller University: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Folic Acid; DNA Methylation; Gene Expression Profiling; Microarray Analysis; Amplified Fragment Length Polymorphism Analysis

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Methylation; Alkylation; Biochemical Phenomena; Chemical Phenomena; Metabolism; Genetic Phenomena; Genetic Techniques; Investigative Techniques; Microchip Analytical Procedures; DNA Fingerprinting; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques

Study Officials

• Peter R. Holt, MD

  Rockefeller University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: SINGLE
• Purpose: PREVENTION
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 7, 2008
• First Posted: February 8, 2008
• Study Start: June 1, 2003
• Primary Completion: January 1, 2006
• Last Updated: February 17, 2009

Record last verified: 2008-02