Effect of Folate on Colon and Blood Cells

NCT ID: NCT00220012

Last Updated: 2013-11-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2008-09-30

Brief Summary

This study looks at the effect of folate supplementation and depletion on the blood cells and the colorectal cells. To examine the effect of these changes, blood samples and colorectal biopsy samples are collected. The genetic material (RNA and DNA) is examined to see what changes occur during the depletion and supplementation of folate. The hypothesis is that folate may help prevent colon cancer

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.

Conditions

Subjects Will Have a Pre-cancerous Colorectal Polyp; Family Member Has History of Colorectal Adenoma of Adenocarcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Interventions

Folate depletion and supplementation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. 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).

2. 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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 72 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Rockefeller University

OTHER

Sponsor Role: lead

Principal Investigators

Peter Holt, MD

Role: PRINCIPAL_INVESTIGATOR

Rockefeller University and Strang Cancer Institute

Locations

Rockefeller University Hospital

New York, New York, United States

Countries

United States

References

Protiva P, Mason JB, Liu Z, Hopkins ME, Nelson C, Marshall JR, Lambrecht RW, Pendyala S, Kopelovich L, Kim M, Kleinstein SH, Laird PW, Lipkin M, Holt PR. Altered folate availability modifies the molecular environment of the human colorectum: implications for colorectal carcinogenesis. Cancer Prev Res (Phila). 2011 Apr;4(4):530-43. doi: 10.1158/1940-6207.CAPR-10-0143. Epub 2011 Feb 14.

Reference Type: DERIVED

PMID: 21321062 (View on PubMed)

Related Links

http://www.rucares.org

Related Info

Other Identifiers

N01-CN-35111

Identifier Type: -

Identifier Source: secondary_id

PHO-0514

Identifier Type: -

Identifier Source: org_study_id