Effect of Folate on Colon and Blood Cells
Effect of Folate on Colonic and Blood Cells
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Folate Depletion Arm and Supplementation Arm:
The folate depletion study requires an 8-week run-in period. During this run-in period, all participants will eat an average folate diet with no high folate containing foods. There are two screening visits during this period where initial blood-work is done and participants undergo nutritional consultation. Following the 8-week run-in period, subjects in the folate depletion arm will be hospitalized for approximately 3 months at the Rockefeller University Hospital. You may leave the hospital during the day, but are required to return each evening. During this entire time, subjects are given a low folate diet. During the last month of the study, folate supplements are given to replace folate in the body. A follow-up visit is required approximately 1 month after the study period. Blood will be drawn every two weeks. Four sigmoidoscopies will be taken at approximately monthly intervals. A male is required to use an effective form of birth control throughout his participation in the study and for two months after the study ends.
The folate supplementation study requires an 8-week run-in period. During this run-in period, all participants will eat an average folate diet with no high folate containing foods. There are two screening visits during this period where initial blood-work is done and participants undergo nutritional consultation. Following the 8-week run-in period, subjects in the folate supplementation arm will be given a folate supplement for 8 weeks. During this entire time, subjects will continue to eat an average folate diet with no high folate containing foods. Blood samples and colorectal mucosa samples obtained during a sigmoidoscopy will be taken 3 times at 4 week intervals.
Study Type
Enrollment
Phase
- Phase 1
Contacts and Locations
Study Locations
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New York
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New York, New York, United States, 10021
- Rockefeller University Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Men or post-menopausal women ages 40 to 72 years old that have a personal history of colorectal adenomatous polyps and/or have a family history of colorectal cancer or polyps will be included. Women have to be ≥2 years post-menopause (2 years after the last menstrual period).
- Ambulatory and in good health. -
Exclusion Criteria:
1. Personal history of cancer other than non-melanoma skin cancer.
2. History of hereditary non-polyposis colon cancer or more that one first degree family member with colorectal or endometrial cancers.
3. Diseases of the bowel such as intestinal malabsorption or inflammatory bowel disease
4. Surgery to the stomach or colon not including removal of the appendix or surgery to the esophagus (food tube)
5. Any excessive bleeding or clotting disorder or if you are taking blood thinners.
6. Abnormalities of or conditions predisposing you to abnormalities of, folate metabolism.
7. Untreated hyperthyroidism (increase in thyroid function) or insulin-requiring diabetes mellitus
8. Daily alcohol intake greater than 2 ½ shot glasses of whisky or three -8 ounce glasses of beer or wine.
9. No regular dosing of 660 mg of aspirin per day or more than 660 mg per day
This is equal to or more than two tablets of 325 mg. of regular strength aspirin; or equal to or more than one tablet of 500 mg. extra-strength aspirin. You must not have regularly taken dosages of nonsteroidal anti-inflammatory agents (NSAID's) within the last 3 months. One example of an NSAID is ibuprofen.
If you have been taking aspirin for heart or blood vessel protection regularly for at least one month before your first screening visit, you will remain on that same amount of medicine throughout the study and is allowed as follows:
- Aspirin 1 to 2 regular aspirin tablets (325 mg per tablet) per day, or
Baby aspirin per day (81mg tablet).
10. A blood level (plasma) Vitamin B12 level less than 250pg/mL or a folate level greater than 20 ng/ml
11. A blood (plasma) homocysteine level equal to or greater than 17 μmol/L
12. Taking a medication called, sterol-binding resins, such as cholestyramine (Questran ®), which is for the treatment of high blood cholesterol.
13. Taking other investigational medications or multiple other medications that might, in the opinion of the investigator, alter cell production in your rectum; folate metabolism, or kidney or liver metabolism.
14. Any serious illness that would be anticipated to limit life expectancy to less than 6 months
15. Sustained elevated blood pressure greater than 150/95 mm Hg for three consecutive readings.
16. Clinically significant liver disease as evidenced by blood levels of alanine amniotransferase or aspartate amniotransferase, greater than two times the upper limits of the normal range, unexplained elevated alkaline phosphatase, or kidney disease with blood creatinine level greater than 2.0 mg/dL.
17. HIV positive test results.
18. Currently taking any of the following:
- Weight control medications.
- Folic acid containing medications greater than 400 micrograms per day.
- Hormone replacement therapies or oral, transplanted, and injected contraceptives.
Thyroid hormone replacement medications
o These will be only allowed if you have been stable on thyroid medication (euthyroid) for three months.
- Medication interfering with the folic acid metabolic effects such as methotrexate (includes Folex® and Trexall® and others), antiepileptic drugs such as phenytoin (Dilantin®), phenobarbital, primidone or sulfonamides (includes some antimicrobial agents) and folinic acid derivatives (Leucovorin®).
- Lipid-lowering medications (with the following exceptions)
If you have been taking the following lipid lowering medication of the class called "statins" regularly for at least one month before your first screening visit, you will remain on the same amount of medicine throughout the study.
- Atorvastatin (Lipitor©) 10 or 20 mg/day
- Fluvastatin (Lescol©) 20 mg or 40 mg/day
- Lovastatin (Levacor©) 10 or 20 mg/day
- Pravastatin (Pravachol©) 10 or 20 mg/day
- Simivastatin (Zocor©) 5 or 10 mg/day
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: Single
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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Measurements of established folate-related endpoints in DNA from blood mononuclear cells and rectal cells:
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Luracil incorporation in blood mononuclear cells
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Strand breaks in the coding region of p53 in blood cells and rectal biopsy cells
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DNA methylation (overall, p53, coding, p16 promotor. MLH1 promotor) in blood cells and rectal biopsy cells
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Secondary Outcome Measures
Outcome Measure |
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Measurements of differential gene expression in colonic and blood cells by microarray analysis, further defining folate's action in modifying cell cycle activity, cell maturation, signal transduction and oncogene expression.
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Peter Holt, MD, Rockefeller University and Strang Cancer Institute
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PHO-0514
- N01-CN-35111
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