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Effect of Vitamin D and Calcium on Genes in the Colon

Primary Purpose

Colorectal Polyps, Colorectal Adenoma, Adenocarcinoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
placebo and Calcitriol
Calcium and Calcitriol
Sponsored by
Rockefeller University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Colorectal Polyps

Eligibility Criteria

48 Years - 72 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Volunteers with a history of pre-cancerous colorectal polyps and/or have a family history of pre-cancerous polyps or colon cancer Not taking any medications known to affect either calcium metabolism or colon function Between the ages of 48 and 72 years old Have had pre-cancerous colorectal polyps or have first or second degree relatives with colorectal cancer and are therefore at increased risk for the disease Exclusion Criteria: Personal history of cancer other than non-melanoma skin cancer Diseases of the bowel such as intestinal malabsorption or inflammatory bowel disease Prior gastrointestinal surgery including gastrectomy, small or large bowel resections. (If one has had an appendectomy or surgery of the esophagus, he/she is still eligible.) Any excessive bleeding or clotting disorders Taking blood thinners Abnormalities of or conditions predisposing one to abnormalities of calcium metabolism. (This includes untreated hyperparathyroidism [increase in parathyroid function] and history of milk-alkali syndrome, a type of calcium metabolism disease.) Untreated hyperthyroidism (increase in thyroid function) Regularly take greater than 660 mg of aspirin per day. This is greater than two tablets of 325 mg regular strength aspirin or greater than one tablet of 500 mg of extra strength aspirin per day. (If one has been taking aspirin for heart or blood vessel protection regularly for at least one month before his/her first screening visit, he/she will remain on the same amount of medicine throughout the study. The following amounts are acceptable: Aspirin 1 to 2 regular tablets (325 mg) per day, or Baby aspirin 1 tablet (81 mg) per day Regularly take daily dosages of nonsteroidal anti-inflammatory agents (NSAIDs) within the last 3 months. (One example of an NSAID is ibuprofen.) Taking greater than 1200 mg of dietary calcium daily Taking medications called sterol-binding resins, such as cholestyramine (Questran®), which is for the treatment of high blood cholesterol Taking other investigational drugs or multiple other medications that might, in the opinion of the investigator, affect the study measurements. Other serious illness(es) that are anticipated to limit life expectancy to less than 6 months Elevated blood pressure greater than 160/100 mmHg HIV positive Pregnant or nursing A history of kidney stones Liver disease and/or kidney disease Diabetes mellitus High "bad" cholesterol level, low density lipoprotein (LDL) greater than 175 mg/dl or triglyceride levels greater than 600 mg/dl Known history of coronary artery disease EKG (electrocardiogram is a record of the electrical activity of the heart) changes consistent with a past heart attack (myocardial infraction) Currently taking: Antidiabetic medication Hormone replacement therapies, oral, injected or implanted contraceptives. (Thyroid hormone replacement is allowed as long as one's thyroid test is normal.) Vitamin, mineral, fish oil, and herbal supplementation and weight control medication must be stopped at least 1 month prior to enrolling in the study.

Sites / Locations

  • Rockefeller University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

placebo and Calcitriol

2

Arm Description

placebo tablets together with an oral tablet of 1, 25 dihydroxy vitamin D3 (Calcitriol)

calcium together with an oral tablet of 1, 25 dihydroxy vitamin D3 (Calcitriol)

Outcomes

Primary Outcome Measures

Gene expression related to proliferation, apoptosis, and differentiation of human rectal mucosal cells

Secondary Outcome Measures

Expression of additional genes involved in the cell properties noted above

Full Information

First Posted
March 1, 2006
Last Updated
November 17, 2011
Sponsor
Rockefeller University
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1. Study Identification

Unique Protocol Identification Number
NCT00298545
Brief Title
Effect of Vitamin D and Calcium on Genes in the Colon
Official Title
High vs. Low Calcium Intake in the Presence of High Vitamin D: Effect on Gene Expression in the Colon
Study Type
Interventional

2. Study Status

Record Verification Date
November 2011
Overall Recruitment Status
Completed
Study Start Date
November 2005 (undefined)
Primary Completion Date
May 2009 (Actual)
Study Completion Date
May 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rockefeller University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The researchers are involved in a research program to understand how vitamin D and calcium in the diet or as supplements may lower the risk of colorectal polyps and cancer. To that end, the researchers are conducting a study of vitamin D supplementation in which volunteer subjects are provided a Western style diet for 2 separate 4 week periods at the Rockefeller University Hospital. During one of these 4 week inpatient periods, subjects receive calcium supplements and during the other 4 week inpatient period they receive a placebo tablet. The researchers determine changes within the colon as a result of supplementing the vitamin D in the presence of high and low calcium. A more detailed description of the study is provided below.
Detailed Description
Study subjects participate for about 3 months. During this time, there is one outpatient visit, a 4 week inpatient period, a 4 week outpatient period known as a wash out period and finally another 4 week inpatient period. During the inpatient periods, the Rockefeller University Hospital (RUH) becomes your home. The subject must sleep here every night and consume all the food provided. During the screening visit, blood and urine samples will be taken and an EKG (electrocardiogram) and a complete physical exam will be done. After enrollment into the study, the first 4 week inpatient period begins. You may continue to go to work or do other activities as long as you eat the diet provided and sleep at the Rockefeller University Hospital. You must eat everything that we give you and you may not substitute or supplement the diet in any way. During each 4 week stay at the Rockefeller University Hospital, there will be three flexible sigmoidoscopies done and biopsies taken of the mucosal lining of the colorectum. This procedure is painless and takes about 5 minutes. In addition, blood samples will be taken every few days for follow-up and research, and two 24 hour urine samples will be done on separate days during the hospitalization. Vital signs are measured every day and your weight will be measured three times per week. During the four week wash out period, the subject will return to their home, go about their normal activities and consume their normal diet. The subject will return to the Rockefeller University Hospital for the second 4 week inpatient period. The procedures and laboratory tests are the same during the second inpatient period. The study concludes with the subjects' discharge from the RUH.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Polyps, Colorectal Adenoma, Adenocarcinoma

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
placebo and Calcitriol
Arm Type
Placebo Comparator
Arm Description
placebo tablets together with an oral tablet of 1, 25 dihydroxy vitamin D3 (Calcitriol)
Arm Title
2
Arm Type
Active Comparator
Arm Description
calcium together with an oral tablet of 1, 25 dihydroxy vitamin D3 (Calcitriol)
Intervention Type
Drug
Intervention Name(s)
placebo and Calcitriol
Intervention Description
Placebo tablets twice daily together with an oral tablet of 1, 25 dihydroxy vitamin D3 (Calcitriol)
Intervention Type
Drug
Intervention Name(s)
Calcium and Calcitriol
Intervention Description
Calcium twice daily together with an oral tablet of 1, 25 dihydroxy vitamin D3 (Calcitriol)
Primary Outcome Measure Information:
Title
Gene expression related to proliferation, apoptosis, and differentiation of human rectal mucosal cells
Time Frame
end of study
Secondary Outcome Measure Information:
Title
Expression of additional genes involved in the cell properties noted above
Time Frame
end of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
48 Years
Maximum Age & Unit of Time
72 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Volunteers with a history of pre-cancerous colorectal polyps and/or have a family history of pre-cancerous polyps or colon cancer Not taking any medications known to affect either calcium metabolism or colon function Between the ages of 48 and 72 years old Have had pre-cancerous colorectal polyps or have first or second degree relatives with colorectal cancer and are therefore at increased risk for the disease Exclusion Criteria: Personal history of cancer other than non-melanoma skin cancer Diseases of the bowel such as intestinal malabsorption or inflammatory bowel disease Prior gastrointestinal surgery including gastrectomy, small or large bowel resections. (If one has had an appendectomy or surgery of the esophagus, he/she is still eligible.) Any excessive bleeding or clotting disorders Taking blood thinners Abnormalities of or conditions predisposing one to abnormalities of calcium metabolism. (This includes untreated hyperparathyroidism [increase in parathyroid function] and history of milk-alkali syndrome, a type of calcium metabolism disease.) Untreated hyperthyroidism (increase in thyroid function) Regularly take greater than 660 mg of aspirin per day. This is greater than two tablets of 325 mg regular strength aspirin or greater than one tablet of 500 mg of extra strength aspirin per day. (If one has been taking aspirin for heart or blood vessel protection regularly for at least one month before his/her first screening visit, he/she will remain on the same amount of medicine throughout the study. The following amounts are acceptable: Aspirin 1 to 2 regular tablets (325 mg) per day, or Baby aspirin 1 tablet (81 mg) per day Regularly take daily dosages of nonsteroidal anti-inflammatory agents (NSAIDs) within the last 3 months. (One example of an NSAID is ibuprofen.) Taking greater than 1200 mg of dietary calcium daily Taking medications called sterol-binding resins, such as cholestyramine (Questran®), which is for the treatment of high blood cholesterol Taking other investigational drugs or multiple other medications that might, in the opinion of the investigator, affect the study measurements. Other serious illness(es) that are anticipated to limit life expectancy to less than 6 months Elevated blood pressure greater than 160/100 mmHg HIV positive Pregnant or nursing A history of kidney stones Liver disease and/or kidney disease Diabetes mellitus High "bad" cholesterol level, low density lipoprotein (LDL) greater than 175 mg/dl or triglyceride levels greater than 600 mg/dl Known history of coronary artery disease EKG (electrocardiogram is a record of the electrical activity of the heart) changes consistent with a past heart attack (myocardial infraction) Currently taking: Antidiabetic medication Hormone replacement therapies, oral, injected or implanted contraceptives. (Thyroid hormone replacement is allowed as long as one's thyroid test is normal.) Vitamin, mineral, fish oil, and herbal supplementation and weight control medication must be stopped at least 1 month prior to enrolling in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Holt, MD
Organizational Affiliation
Rockefeller University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rockefeller University Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
27009752
Citation
Protiva P, Pendyala S, Nelson C, Augenlicht LH, Lipkin M, Holt PR. Calcium and 1,25-dihydroxyvitamin D3 modulate genes of immune and inflammatory pathways in the human colon: a human crossover trial. Am J Clin Nutr. 2016 May;103(5):1224-31. doi: 10.3945/ajcn.114.105304. Epub 2016 Mar 23.
Results Reference
derived

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Effect of Vitamin D and Calcium on Genes in the Colon

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