- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01472445
Vitamin D and Breast Cancer: Does Weight Make a Difference?
Study Overview
Detailed Description
Vitamin D3 (cholecalciferol, colecalciferol) is one of type of vitamin D which is made by the skin when exposed to sunlight; it is also found in some foods and can be taken as a dietary supplement. It is used to treat and prevent vitamin D deficiency and associated diseases, including rickets. Vitamin D3 may have a role obesity and cancer biology. In the body, Vitamin D3 is metabolized to the active form 1,25-dihydroxycholecalciferol (calcitriol, 1,25-(OH)2vitamin D3).
This protocol is a randomized, controlled, and blinded clinical trial in obese and non-obese breast cancer patients in whom the effects of vitamin D supplementation will be evaluated in the neoadjuvant setting. Changes in biomarker expression levels in blood will be assessed from baseline to post-treatment (post-surgery).
Per protocol (see title), the treatment groups are defined as those participants with body mass index (BMI) ≤ 25 ("non-obese") and > 25 ("obese"). Within each treatment group, dose of Vitamin D3 was stratified between 400 IU/day (control) and 10,000 IU/day (experimental). All analyses were typically conducted between BMI cohorts stratified by Vitamin D3 dose.
Protocol Primary Objective: "To determine whether dietary vitamin D can reverse the negative effects of obesity and insulin resistance as reflected by changes in breast cancer gene expression patterns in obese and non obese subjects diagnosed with breast cancer."
Protocol Secondary Objectives: "To determine whether dietary vitamin D can reverse the negative effects of obesity and insulin resistance as reflected by serum biomarkers of insulin resistance and adipokine secretion in obese and non obese subjects diagnosed with breast cancer."
The following markers will be part of this study.
- Insulin-like growth factor-binding protein 3 (IGFBP-3) is a Vitamin D target, and the most abundant of 6 different IGFBPs. The insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) binds to IGFBP-3 with high affinity, which helps lengthen the half-life of circulating IGFs in all tissues. Through this binding action, IGFBP-3 exerts anti-proliferative effects by blocking the ability of IGFs to activate the IGF-1 receptor (IGF1R, which stimulates cell proliferation). IGFBP-3 levels were assessed on the basis of mRNA levels.
- p21 [also known as p21Cip1; p21Waf1, cyclin-dependent kinase inhibitor 1 (CDKI1) or cyclin-dependent kinase (CDK)-interacting protein 1 (CDKIP1)] is the primary mediator of p53-dependent cell cycle arrest in response to DNA damage, and is a proliferation; apoptosis; and invasion biomarker. p21 is primarily associated with inhibition of CDK2, but is capable of inhibiting all cyclin/CDK complexes. p21 3 levels were assessed on the basis of mRNA levels.
- Matrix metalloproteinase-11 (MMP-11), aka Stromelysin-3 (SL-3), is involved in the breakdown of extracellular matrix in the disease processes of metastasis and arthritis, as well as various normal physiological processes, such as embryonic development, reproduction, and tissue remodeling. MMP-11 levels were assessed on the basis of mRNA levels.
- Ki-67 ("Antigen Identified By Monoclonal Antibody Ki-67", Antigen Ki67) is the protein produced by the gene MKI67, and is a nuclear protein that is associated with cellular proliferation and ribosomal RNA transcription. Ki-67 is a recognized biomarker for mitotic rate and cellular, but is absent in resting (quiescent) cells (Stage G0). In breast cancer, Ki67 identifies a subset of patients with ER-positive breast cancer that is highly proliferative, and who derive greater benefit from adjuvant chemotherapy. MKI67 levels were assessed on the basis of mRNA levels.
- ESR1 is the gene encoding estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), and is a nuclear receptor that is activated by the sex hormone estrogen. ERα plays a role in the physiological development and function of a variety of organ systems to varying degrees, including the reproductive, central nervous, skeletal, and cardiovascular systems. Genetic polymorphisms in ESR1 have been associated with breast cancer. ESR1 levels were assessed on the basis of mRNA levels.
- Leptin is a stimulator of adipose stromal cell estrogen synthesis and a breast cancer growth promoter. Serum levels of leptin correlate with body mass index (BMI, a measure of obesity) and breast cancer risk. Leptin receptors are expressed by breast cancer cells and leptin can promote (regulate) breast cancer cell proliferation. Leptin levels were measured by Western blot or immunohistochemical (IHC) methodology.
- Adiponectin inhibits breast cancer growth. Adiponectin receptors are expressed by breast cancer cells and adiponectin can inhibit (regulate) breast cancer cell proliferation by stimulating apoptosis in estrogen receptor (ER)+ Breast cancer cells and suppressing estrogen-stimulated cell growth. Adiponectin levels were measured by Western blot or immunohistochemical (IHC) methodology.
- Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) is a standard determination of insulin resistance based on fasting insulin and glucose levels.
- cRP (C-reactive protein) is an inflammation marker produced by the liver. High levels of CRP in the blood are indicative of a wide variety of conditions, including cancer. cRP levels were measured by Western blot or immunohistochemical (IHC) methodology.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
-
Stanford, California, United States, 94305
- Stanford University Cancer Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Women who have undergone a core needle biopsy demonstrating an operable breast cancer whom have not yet had any further therapy.
- No prior therapy for breast cancer.
- Age 18 years or older.
- Any menopausal status
- Planned surgical resection of breast cancer or repeat core biopsy tissue sampling prior to initiation of neoadjuvant systemic chemotherapy.
- Availability of tissue blocks from initial core needle biopsy.
- Signed informed consent.
- Willing to discontinue use of all supplements containing Vitamin D for the duration of the study, and take only the Vitamin D provided by the study.
Exclusion Criteria:
- Presence of any Metastatic lesion.
- History of parathyroid disease, hypercalcemia, or kidney stones.
- History of Selective estrogen receptor modulator (SERM) or aromatase inhibitor therapy.
- Receiving metformin.
- History of renal failure requiring dialysis or kidney transplantation.
- Women who are known to be pregnant or who are nursing. (As vitamin D does not have toxicity to the fetus, a negative pregnancy test is not a requirement to participate in the study.)
- Patients planned for surgical therapy of their breast cancer or initiation of systemic chemotherapy, that would not allow for at least 7 days of vitamin D intervention
- Any condition potentially interfering with subjects ability to comply with taking study medication.
- Any medical condition that would potentially interfere with vitamin D absorption.
- Current participation in another research study that would increase risk to subject, in the opinion of the investigators.
- Patients currently taking more than 2000 IU of Vitamin D.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Non-obese (Body Mass Index ≤ 25)
Non-obese participants receive Vitamin D at 400 or 10,000 IU/day
|
Other Names:
|
Experimental: Obese (Body Mass Index > 25)
Obese participants receive Vitamin D at 400 or 10,000 IU/day
|
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Expression Level of Insulin-like Growth Factor-binding Protein 3 (IGFBP-3) Gene
Time Frame: up to 6 weeks
|
To determine whether dietary vitamin D can reverse the negative effects of obesity and insulin resistance as reflected by changes in breast cancer gene expression patterns in obese and non-obese subjects diagnosed with breast cancer. IGFBP-3 is an endocrine factors. Insulin-like growth factor-binding protein 3 (IGFBP-3) gene expression was assessed at baseline and after treatment in participants with body mass index (BMI) ≤ 25 and > 25. By design, the outcome was determined for non-obese vs obese participants stratified between 400 IU/day (control) and 10,000 IU/day (experimental), and is reported as the mean of the slope (a measure of magnitude of difference) between baseline and post-treatment, with standard deviation. A positive slope indicates increased expression, and a negative slope indicates decreasing values, with the larger values (positive or negative) indicating greater effect, and smaller values indicating lesser effect. |
up to 6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Expression Level of Cyclin-dependent Kinase Inhibitor 1 (CDKI1; p21) Gene
Time Frame: up to 6 weeks
|
p21 [aka p21Cip1; p21Waf1, cyclin-dependent kinase inhibitor 1 (CDKI1) or cyclin-dependent kinase (CDK)-interacting protein 1 (CDKIP1)] gene expression was assessed at baseline and after treatment in participants with body mass index (BMI) ≤ 25 and > 25.
By design, the outcome was determined for non-obese vs obese participants stratified between 400 IU/day (control) and 10,000 IU/day (experimental), and is reported as the mean of the slope (a measure of magnitude of difference) between baseline and post-treatment, with standard deviation.
A positive slope indicates increased expression, and a negative slope indicates decreasing values, with the larger values (positive or negative) indicating greater effect, and smaller values indicating lesser effect.
|
up to 6 weeks
|
Expression Level of Matrix Metalloproteinase-11 (MMP-11) Gene
Time Frame: up to 6 weeks
|
Matrix metalloproteinase-11 (MMP-11), aka Stromelysin-3 (SL-3), gene expression was assessed at baseline and after treatment in participants with body mass index (BMI) ≤ 25 and > 25.
By design, the outcome was determined for non-obese vs obese participants stratified between 400 IU/day (control) and 10,000 IU/day (experimental), and is reported as the mean of the slope (a measure of magnitude of difference) between baseline and post-treatment, with standard deviation.
A positive slope indicates increased expression, and a negative slope indicates decreasing values, with the larger values (positive or negative) indicating greater effect, and smaller values indicating lesser effect.
|
up to 6 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Expression Level of MKI67 Gene
Time Frame: up to 6 weeks
|
Ki 67 gene expression was assessed at baseline and after treatment in participants with body mass index (BMI) ≤ 25 and > 25.
By design, the outcome was determined for non-obese vs obese participants stratified between 400 IU/day (control) and 10,000 IU/day (experimental), and is reported as the mean of the slope (a measure of magnitude of difference) between baseline and post-treatment, with standard deviation.
A positive slope indicates increased expression, and a negative slope indicates decreasing values, with the larger values (positive or negative) indicating greater effect, and smaller values indicating lesser effect.
|
up to 6 weeks
|
Expression Level of ESR1 Gene
Time Frame: up to 6 weeks
|
ESR1 gene expression was assessed at baseline and after treatment in participants with body mass index (BMI) ≤ 25 and > 25.
By design, the outcome was determined for non-obese vs obese participants stratified between 400 IU/day (control) and 10,000 IU/day (experimental), and is reported as the mean of the slope (a measure of magnitude of difference) between baseline and post-treatment, with standard deviation.
A positive slope indicates increased expression, and a negative slope indicates decreasing values, with the larger values (positive or negative) indicating greater effect, and smaller values indicating lesser effect.
|
up to 6 weeks
|
Leptin to Adiponectin Ratio (Leptin:Adiponectin) in Blood
Time Frame: up to 6 weeks
|
Levels in blood of leptin & adiponectin were assessed at baseline & after treatment in participants with body mass index ≤25 and >25.
By protocol design, the outcome was determined for non-obese vs obese participants stratified between 400 IU/day and 10,000 IU/day.
For all serum protein levels, the outcome is reported as the ratio of the baseline to post-treatment values (baseline:post-treatment) of the ratio of the mean serum levels of leptin and adiponectin, (ie, lepton:adiponectin).
As a ratio of the ratio of means, the outcome is reported as a number without dispersion.
The outcome value expresses the treatment effect on both leptin and adiponectin collectively, with a value <1.00 meaning that the effect on leptin levels was reduced relative to the effect on adiponectin levels, and a value >1.00 that the effect on leptin levels was increased relative to the effect on adiponectin levels, with a larger difference from 1.00 indicating a greater effect (1.00 means no measure change).
|
up to 6 weeks
|
HOMA-IR to Adiponectin Ratio (HOMA-IR:Adiponectin) in Blood
Time Frame: up to 6 weeks
|
The Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR) was used to assess fasting insulin & glucose levels.
HOMA-IR & adiponectin were assessed at baseline & after treatment in participants with body mass index ≤25 and >25.
By protocol design, the outcome is for non-obese vs obese participants stratified between 400 & 10,000 IU/day.
For all serum protein levels, the outcome is reported as the ratio of the baseline to post-treatment values (baseline:post-treatment) of the ratio of the mean serum levels of leptin & adiponectin, (ie, lepton:adiponectin).
As a ratio of the ratio of means, the outcome is reported as a number without dispersion.
The outcome expresses the treatment effect on HOMA-IR & adiponectin collectively, with <1.00 meaning effect on HOMA-IR levels is reduced relative to the effect on adiponectin levels, & >1.00 meaning the effect is increased relative, with a greater difference meaning greater effect (1.00 represents no measure change).
|
up to 6 weeks
|
cRP (C-reactive Protein) to Adiponectin Ratio (cRP:Adiponectin) in Blood
Time Frame: up to 6 weeks
|
Levels in blood of cRP (C-reactive protein) & adiponectin were assessed at baseline & after treatment in participants with body mass index (BMI) ≤25 and >25.
By protocol design, the outcome was determined for non-obese vs obese participants stratified between 400 IU/day & 10,000 IU/day.
For all serum protein levels, the outcome is the ratio of the baseline to post-treatment values (baseline:post-treatment) of the ratio of the mean serum levels of leptin & adiponectin, (ie, lepton:adiponectin).
As a ratio of the ratio of means, the outcome is reported as a number without dispersion.
The outcome value expresses the treatment effect on cRP and adiponectin collectively, with a value < 1.00 meaning effect on cRP levels was reduced relative to the effect on adiponectin levels, and a value > 1.00 meaning effect on cRP levels was increased relative to the effect on adiponectin levels, with a larger difference from 1.00 indicating a greater effect (1.00 represents no measure change).
|
up to 6 weeks
|
Pharmacokinetics of Vitamin D Metabolite Calcitriol
Time Frame: up to 6 weeks
|
Blood levels (pharmacokinetics) of Vitamin D were evaluated as the blood levels of Vitamin D metabolite calcitriol (also known as 1,25-dihydroxycholecalciferol or 1,25(OH)2D) in participants receiving 400 IU/day Vitamin D. The outcome is reported as the mean calcitriol level pre-treatment and post-treatment, with standard deviation.
|
up to 6 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Melinda Telli, MD, Stanford University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB-21034
- SU-09262011-8486 (Other Identifier: Stanford University)
- BRSADJ0024 (Other Identifier: OnCore)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Breast Cancer
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); Rutgers Cancer Institute of New JerseyActive, not recruitingStage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative Breast CancerUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedMale Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
University of WashingtonTerminatedBreast Cancer | Breast Cancer Stage I | Breast Cancer Stage II | Breast Cancer Stage III | Breast Cancer Stage IIB | Breast Cancer Stage IIA | Breast Cancer Stage IIIA | Breast Cancer Stage IIIB | Breast Cancer Stage IIIcUnited States
-
CelgeneCompletedBreast Cancer | Metastatic Breast Cancer | Stage IV Breast Cancer | Triple-negative Breast Cancer | Recurrent Breast Cancer | Breast Tumor | Cancer of the Breast | Triple-negative Metastatic Breast Cancer | Estrogen Receptor- Negative Breast Cancer | HER2- Negative Breast Cancer | Progesterone Receptor- Negative...United States, United Kingdom, Italy, Germany, Spain, Canada, Portugal, Australia, Austria, Greece, Brazil, France
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedHER2-positive Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Estrogen Receptor-negative Breast Cancer | Estrogen Receptor-positive Breast Cancer | Progesterone Receptor-negative Breast Cancer | Progesterone Receptor-positive Breast...United States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Male Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Susan G. Komen Breast Cancer FoundationCompletedStage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative Breast CancerUnited States
-
Northwestern UniversityEisai Inc.UnknownMale Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative...United States
-
Ohio State University Comprehensive Cancer CenterCompletedStage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Stage III Breast CancerUnited States
Clinical Trials on Vitamin D
-
PfizerTerminated
-
Umeå UniversityRegion SkaneCompleted
-
Khon Kaen UniversityNot yet recruiting
-
Fundación Cardiovascular de ColombiaUniversidad Industrial de Santander; Farma de Colombia SACompletedVitamin D Deficiency | Overweight and Obesity | Overweight AdolescentsColombia
-
Nutrition Institute, SloveniaSlovenian Research Agency; Higher School of Applied Sciences (VIST); Valens Int...CompletedVitamin D DeficiencySlovenia
-
USDA, Western Human Nutrition Research CenterCompletedVitamin D DeficiencyUnited States
-
University of AarhusNot yet recruitingImmune System Diseases | Growth | Child Development | Vitamin D Supplementation
-
Cornell UniversityArogyavaram Medical CentreNot yet recruiting
-
University Hospital, Basel, SwitzerlandCompleted
-
Brigham and Women's HospitalNational Heart, Lung, and Blood Institute (NHLBI)Active, not recruiting