The Effects of Vitamin B-6 Status on Homocysteine, Oxidative Stress, One-carbon Metabolism and Methylation: Cross-section, Case-control, Intervention and Follow-up Studies in Colorectal Cancer

Vitamin B-6, folate and homocysteine may play a critical role in the colorectal cancer progression. This is a 4-y study and the specific aims are: 1) to compare vitamin B-6, folate and homocysteine status, oxidative stress, antioxidant activities and DNA methylation between subjects with colorectal polyps and colorectal cancer; 2) to study the effects of vitamin B-6, folate and homocysteine status on oxidative stress, antioxidant activities and DNA methylation in colorectal cancer patients; 3) to evaluate whether folic acid and/or pyridoxine supplementation had a beneficial effect on oxidative stress, antioxidant activities and DNA methylation in patients with colorectal; 4) to compare vitamin B-6, folate and homocysteine status, oxidative stress, antioxidant activities and DNA methylation between colorectal cancer patients and age-, sex-matched healthy subjects; 5) to evaluate the effect of vitamin B-6, folate and homocysteine status, oxidative stress, antioxidant activities and DNA methylation on the risk of colorectal cancer (odds ratio); 6) to follow the effects of vitamin B-6, folate and homocysteine status, oxidative stress, antioxidant activities and DNA methylation on the occurrence of colorectal cancer; 7) to follow the effects of pyridoxine and/or folic acid supplementation on the occurrence of colorectal cancer.

This protocol is designed as a hospital-based cross-sectional, case-control, double blinded randomized placebo-controlled intervention and follow-up trial. Three hundred colorectal cancer patients and 300 age-, sex-matched controls who meet the inclusion criteria will be recruited from Taichung General Veterans Hospital. If cancer patients' plasma pyridoxal 5'-phosphate (PLP) level less than 30 nmol/L will be asked to participate the intervention study and will be blinded and randomly assigned to either the 1) control (vitamin C, 100 mg/d); 2) 50 mg vitamin B-6; 3) 400 microgram/d folic acid; or 4) vitamin B-6 (50 mg/d) plus folic acid (400 microgram/d) for 1 year. Data on demography, anthropometry, medical history, food frequency questionnaire and 24-h diet recall will be collected. Cancer patients will have fasting blood drawn before surgery or receiving chemotherapy. Additionally, fasting blood samples will be obtained at month 0, 3, 6, 9 and 12 during intervention period and at month 6, 12, 18, 24, 30, 36, 42 and 48 during follow-up. Hematological, plasma and erythrocyte PLP, plasma pyridoxal and 4-pyridoxic acid, serum and erythrocyte folate, serum vitamin B-12, homocysteine, SAM, SAH, lipid peroxidation indicators (TBARS, oxidized LDL), glutathione, antioxidant enzymatic activities and DNA methylation and MTHFR 677C>T polymorphism will be measured.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Dietary supplement: Vitamin C; Dietary supplement: Vitamin B6; Dietary supplement: Folic acid; Dietary supplement: Vitamin B6 plus folic acid

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Chiang Feng-Fan; Phone Number: +886-919-710446; Email: hankel.chiang@gmail.com

Study Locations

• Taiwan
  • Taichung, Taiwan
    • Recruiting
    • Taichung Verterans General Hospital
    • Contact: Feng-Fan Chiang, MD; Email: hankel.chiang@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Colorectal cancer participants were identified by colonoscopy to have at least one historically confirmed colorectal cancer.

Exclusion Criteria:

• Age<18 years
• Pregnant women
• Had a history of colorectal cancer
• Attenuated adenomatous polyposis coli
• Inflammatory bowel disease or were taking any medication which could influence homocysteine, folate, vitamin B6 and B12 status, such as H2 blockers, Proton pump inhibitors, metformin, phenytoin, methotrexates.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Vitamin C; Vitamin C as control group.	Dietary supplement: Vitamin C; Vitamin C, 100 mg/d; Other Names: Ascorbic acid
Experimental: Vitamin B6	Dietary supplement: Vitamin B6; Vitamin B6, 50mg/d; Other Names: Pyridoxine
Experimental: Folic acid	Dietary supplement: Folic acid; Folic acid 400 microgram/d; Other Names: Folate
Experimental: Vitamin B6 plus folic acid	Dietary supplement: Vitamin B6 plus folic acid; Vitamin B6, 50 mg; folic acid, 400 microgram; Other Names: B-vitamins (pyridoxine and folate)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antioxidant and DNA methylation	This study are going to measure the oxidative stress (TBARs), antioxidant activities and DNA methylation in colorectal cancer patients	12 months

Collaborators and Investigators

• Sponsor: Taichung Veterans General Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Anticipated): July 1, 2015
• Study Completion (Anticipated): July 1, 2015

Study Registration Dates

• First Submitted: August 29, 2011
• First Submitted That Met QC Criteria: August 30, 2011
• First Posted (Estimate): August 31, 2011

Study Record Updates

• Last Update Posted (Estimate): February 19, 2014
• Last Update Submitted That Met QC Criteria: February 17, 2014
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Antioxidants; Hematinics; Vitamins; Folic Acid; Vitamin B Complex; Ascorbic Acid; Vitamin B 6; Pyridoxal; Pyridoxine
• Other Study ID Numbers: S10251