Subjects Will Have a Pre-cancerous Colorectal PolypPhase 1NCT00220012
Effect of Folate on Colon and Blood Cells
A Phase 1 study testing Folate depletion and supplementation in people with Subjects Will Have a Pre-cancerous Colorectal Polyp and Family Member Has History of Colorectal Adenoma of Adenocarcinoma, run by Rockefeller University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 72 yearsHealthy volunteers can take part
- Conditions the study is for
- Subjects Will Have a Pre-cancerous Colorectal Polyp, Family Member Has History of Colorectal Adenoma of Adenocarcinoma
- What is being tested?
- Folate depletion and supplementation
- Type of treatment
- Surgery or procedure
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2003to Sep 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 72 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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. -
Who cannot join
- 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.
Show all 35Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Rockefeller University Hospital
New York, New York, 10021
About this study
Official title: Effect of Folate on Colonic and Blood Cells
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
Read the 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
- Being tested
- Folate depletion and supplementation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Folate depletion and supplementationProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurements of established folate-related endpoints in DNA from blood mononuclear cells and rectal cells:
Luracil incorporation in blood mononuclear cells
Strand breaks in the coding region of p53 in blood cells and rectal biopsy cells
DNA methylation (overall, p53, coding, p16 promotor. MLH1 promotor) in blood cells and rectal biopsy cells
Secondary outcomes (1)
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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startJun 2003
- Study completionSep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Subjects Will Have a Pre-cancerous Colorectal PolypStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind
- Enrolment
- 20 participants
Sponsor and investigators
- Lead sponsor
- Rockefeller University
- Sponsor type
- University, hospital or other
- Investigators
- Peter Holt, MD, Principal investigator, Rockefeller University and Strang Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00220012
- Sponsor's protocol ID
- PHO-0514
- Other IDs
- N01-CN-35111
- Status last verified
- Nov 2013
- First submitted
- 15 Sep 2005
- Last updated
- 15 Nov 2013
- Results posted
- No
Publications
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.
PubMed 21321062
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Folate on Colonic and Blood Cells
- ClinicalTrials.gov ID
- NCT00220012
- Acronym / sponsor ID
- PHO-0514
- Conditions
- Subjects Will Have a Pre-cancerous Colorectal Polyp, Family Member Has History of Colorectal Adenoma of Adenocarcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants
- Lead sponsor
- Rockefeller UniversityUniversity, hospital or other
- Study start
- Jun 2003
- Study completion
- Sep 2008 (actual)
- First posted
- 22 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind
Who may qualify
- Ages
- 40 to 72 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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. -
Key exclusion criteria (35 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Folate depletion and supplementation | Procedure or surgery | – |
Primary outcome
Measurements of established folate-related endpoints in DNA from blood mononuclear cells and rectal cells:
Luracil incorporation in blood mononuclear cells
Strand breaks in the coding region of p53 in blood cells and rectal biopsy cells
DNA methylation (overall, p53, coding, p16 promotor. MLH1 promotor) in blood cells and rectal biopsy cells
1 secondary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2013.
- Derived from this study: PubMed 21321062Protiva 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.
- Related InfoLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Holt, MD principal investigator
Rockefeller University and Strang Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Folate depletion and supplementation in people with Subjects Will Have a Pre-cancerous Colorectal Polyp and Family Member Has History of Colorectal Adenoma of Adenocarcinoma, run by Rockefeller University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurements of established folate-related endpoints in DNA from blood mononuclear cells and rectal cells:. The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00220012, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2013.