Trial Outcomes & Findings for Vitamin D and Breast Cancer: Does Weight Make a Difference? (NCT NCT01472445)

NCT ID: NCT01472445

Last Updated: 2019-04-19

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 41 participants
• Primary outcome timeframe: up to 6 weeks
• Results posted on: 2019-04-19

Participant Flow

Participant milestones

Measure	Non-obese (Body Mass Index ≤ 25) Non-obese participants receive Vitamin D at 400 or 10,000 IU/day	Obese (Body Mass Index > 25) Obese participants receive Vitamin D at 400 or 10,000 IU/day
Overall Study STARTED	25	16
Overall Study COMPLETED	25	16
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Vitamin D and Breast Cancer: Does Weight Make a Difference?

Baseline characteristics by cohort

Measure	Non-obese (Body Mass Index ≤ 25) n=25 Participants Non-obese participants receive Vitamin D at 400 or 10,000 IU/day	Obese (Body Mass Index > 25) n=16 Participants Obese participants receive Vitamin D at 400 or 10,000 IU/day	Total n=41 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	21 Participants n=5 Participants	7 Participants n=7 Participants	28 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants
Age, Continuous	54.1 years STANDARD_DEVIATION 11.6 • n=5 Participants	62.1 years STANDARD_DEVIATION 7.6 • n=7 Participants	57.3 years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	16 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants	16 participants n=7 Participants	41 participants n=5 Participants

PRIMARY outcome

Timeframe: up to 6 weeks

Population: Study cohorts (non-obese vs obese) are stratified by Vitamin D dose level.

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.

Outcome measures

Measure	Non-obese (Body Mass Index ≤ 25) n=25 Participants Non-obese participants receive Vitamin D at 400 or 10,000 IU/day	Obese (Body Mass Index > 25) n=16 Participants Obese participants receive Vitamin D at 400 or 10,000 IU/day
Expression Level of Insulin-like Growth Factor-binding Protein 3 (IGFBP-3) Gene Vitamin D 400 IU/day	0.02937 ratio baseline:post-treatment (slope) Standard Deviation 0.03792	0.00941 ratio baseline:post-treatment (slope) Standard Deviation 0.00680
Expression Level of Insulin-like Growth Factor-binding Protein 3 (IGFBP-3) Gene Vitamin D 10,000 IU/day	0.0158 ratio baseline:post-treatment (slope) Standard Deviation 0.03645	0.01443 ratio baseline:post-treatment (slope) Standard Deviation 0.01828

SECONDARY outcome

Timeframe: up to 6 weeks

Population: Study cohorts (non-obese vs obese) are stratified by Vitamin D dose level.

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.

Outcome measures

Measure	Non-obese (Body Mass Index ≤ 25) n=25 Participants Non-obese participants receive Vitamin D at 400 or 10,000 IU/day	Obese (Body Mass Index > 25) n=16 Participants Obese participants receive Vitamin D at 400 or 10,000 IU/day
Expression Level of Cyclin-dependent Kinase Inhibitor 1 (CDKI1; p21) Gene Vitamin D 400 IU/day	0.04868 ratio baseline:post-treatment (slope) Standard Deviation 0.07735	0.03465 ratio baseline:post-treatment (slope) Standard Deviation 0.03755
Expression Level of Cyclin-dependent Kinase Inhibitor 1 (CDKI1; p21) Gene Vitamin D 10,000 IU/day	0.02236 ratio baseline:post-treatment (slope) Standard Deviation 0.04859	0.01854 ratio baseline:post-treatment (slope) Standard Deviation 0.01700

SECONDARY outcome

Timeframe: up to 6 weeks

Population: Study cohorts (non-obese vs obese) are stratified by Vitamin D dose level.

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.

Outcome measures

Measure	Non-obese (Body Mass Index ≤ 25) n=25 Participants Non-obese participants receive Vitamin D at 400 or 10,000 IU/day	Obese (Body Mass Index > 25) n=16 Participants Obese participants receive Vitamin D at 400 or 10,000 IU/day
Expression Level of Matrix Metalloproteinase-11 (MMP-11) Gene Vitamin D 400 IU/day	-0.03238 ratio baseline:post-treatment (slope) Standard Deviation 0.04776	-0.00590 ratio baseline:post-treatment (slope) Standard Deviation 0.02441
Expression Level of Matrix Metalloproteinase-11 (MMP-11) Gene Vitamin D 10,000 IU/day	-0.00986 ratio baseline:post-treatment (slope) Standard Deviation 0.05814	-0.02139 ratio baseline:post-treatment (slope) Standard Deviation 0.01961

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 6 weeks

Population: Study cohorts (non-obese vs obese) are stratified by Vitamin D dose level.

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.

Outcome measures

Measure	Non-obese (Body Mass Index ≤ 25) n=25 Participants Non-obese participants receive Vitamin D at 400 or 10,000 IU/day	Obese (Body Mass Index > 25) n=16 Participants Obese participants receive Vitamin D at 400 or 10,000 IU/day
Expression Level of MKI67 Gene Vitamin D 400 IU/day	-0.00958 ratio baseline:post-treatment (slope) Standard Deviation 0.04108	-0.03809 ratio baseline:post-treatment (slope) Standard Deviation 0.02416
Expression Level of MKI67 Gene Vitamin D 10,000 IU/day	-0.01318 ratio baseline:post-treatment (slope) Standard Deviation 0.03231	0.00166 ratio baseline:post-treatment (slope) Standard Deviation 0.01412

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 6 weeks

Population: Study cohorts (non-obese vs obese) are stratified by Vitamin D dose level.

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.

Outcome measures

Measure	Non-obese (Body Mass Index ≤ 25) n=25 Participants Non-obese participants receive Vitamin D at 400 or 10,000 IU/day	Obese (Body Mass Index > 25) n=16 Participants Obese participants receive Vitamin D at 400 or 10,000 IU/day
Expression Level of ESR1 Gene Vitamin D 400 IU/day	0.00526 ratio baseline:post-treatment (slope) Standard Deviation 0.14049	-0.02739 ratio baseline:post-treatment (slope) Standard Deviation 0.02132
Expression Level of ESR1 Gene Vitamin D 10,000 IU/day	-0.05757 ratio baseline:post-treatment (slope) Standard Deviation 0.0747	0.01225 ratio baseline:post-treatment (slope) Standard Deviation 0.04041

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 6 weeks

Population: Study cohorts (non-obese vs obese) are stratified by Vitamin D dose level.

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).

Outcome measures

Measure	Non-obese (Body Mass Index ≤ 25) n=25 Participants Non-obese participants receive Vitamin D at 400 or 10,000 IU/day	Obese (Body Mass Index > 25) n=16 Participants Obese participants receive Vitamin D at 400 or 10,000 IU/day
Leptin to Adiponectin Ratio (Leptin:Adiponectin) in Blood Vitamin D 400 IU/d	0.87 ratio baseline:post-treatment (slope)	1.00 ratio baseline:post-treatment (slope)
Leptin to Adiponectin Ratio (Leptin:Adiponectin) in Blood Vitamin D 10,000 IU/d	0.95 ratio baseline:post-treatment (slope)	1.00 ratio baseline:post-treatment (slope)

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 6 weeks

Population: Study cohorts (non-obese vs obese) are stratified by Vitamin D dose level.

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).

Outcome measures

Measure	Non-obese (Body Mass Index ≤ 25) n=25 Participants Non-obese participants receive Vitamin D at 400 or 10,000 IU/day	Obese (Body Mass Index > 25) n=16 Participants Obese participants receive Vitamin D at 400 or 10,000 IU/day
HOMA-IR to Adiponectin Ratio (HOMA-IR:Adiponectin) in Blood Vitamin D 400 IU/day	0.96 ratio baseline:post-treatment (slope)	0.52 ratio baseline:post-treatment (slope)
HOMA-IR to Adiponectin Ratio (HOMA-IR:Adiponectin) in Blood Vitamin D 10,000 IU/day	1.35 ratio baseline:post-treatment (slope)	0.99 ratio baseline:post-treatment (slope)

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 6 weeks

Population: Study cohorts (non-obese vs obese) are stratified by Vitamin D dose level.

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).

Outcome measures

Measure	Non-obese (Body Mass Index ≤ 25) n=25 Participants Non-obese participants receive Vitamin D at 400 or 10,000 IU/day	Obese (Body Mass Index > 25) n=16 Participants Obese participants receive Vitamin D at 400 or 10,000 IU/day
cRP (C-reactive Protein) to Adiponectin Ratio (cRP:Adiponectin) in Blood Vitamin D 400 IU/day	0.80 ratio baseline:post-treatment (slope)	0.83 ratio baseline:post-treatment (slope)
cRP (C-reactive Protein) to Adiponectin Ratio (cRP:Adiponectin) in Blood Vitamin D 10,000 IU/day	1.33 ratio baseline:post-treatment (slope)	1.00 ratio baseline:post-treatment (slope)

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 6 weeks

Population: All participants are included. Pharmacokinetics results are provided for non-obese vs obese participants, stratified by dose received, and presented as the pre-treatment and post-treatment pharmacokinetic values.

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.

Outcome measures

Measure	Non-obese (Body Mass Index ≤ 25) n=50 Samples for this dose & time Non-obese participants receive Vitamin D at 400 or 10,000 IU/day	Obese (Body Mass Index > 25) n=32 Samples for this dose & time Obese participants receive Vitamin D at 400 or 10,000 IU/day
Pharmacokinetics of Vitamin D Metabolite Calcitriol Pre-treatment, 400 IU/day	30.44 ng/mL Standard Deviation 10.89	34.67 ng/mL Standard Deviation 4.62
Pharmacokinetics of Vitamin D Metabolite Calcitriol Pre-treatment, 10,000 IU/day	30.75 ng/mL Standard Deviation 8.62	37.17 ng/mL Standard Deviation 12.51
Pharmacokinetics of Vitamin D Metabolite Calcitriol Post-treatment, 400 IU/day	30.89 ng/mL Standard Deviation 7.52	31.67 ng/mL Standard Deviation 3.06
Pharmacokinetics of Vitamin D Metabolite Calcitriol Post-treatment, 10,000 IU/day	53.75 ng/mL Standard Deviation 13.82	59.33 ng/mL Standard Deviation 27.74

Adverse Events

Non-obese (Body Mass Index ≤ 25)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Obese (Body Mass Index > 25)

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Non-obese (Body Mass Index ≤ 25) n=25 participants at risk Non-obese participants receive Vitamin D at 400 or 10,000 IU/day	Obese (Body Mass Index > 25) n=16 participants at risk Obese participants receive Vitamin D at 400 or 10,000 IU/day
Metabolism and nutrition disorders Primary hyperparathyroidism (HPT)	0.00% 0/25	6.2% 1/16 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine cancer of the breast, metastatic	0.00% 0/25	6.2% 1/16 • Number of events 1

Other adverse events

Measure	Non-obese (Body Mass Index ≤ 25) n=25 participants at risk Non-obese participants receive Vitamin D at 400 or 10,000 IU/day	Obese (Body Mass Index > 25) n=16 participants at risk Obese participants receive Vitamin D at 400 or 10,000 IU/day
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/25	6.2% 1/16 • Number of events 1
Metabolism and nutrition disorders Plasma chromogranin A level, elevated	0.00% 0/25	6.2% 1/16 • Number of events 1

Additional Information

Melinda Telli, Associate Professor of Medicine (Oncology)

Stanford University

Phone: 650-724-9533

Email: mtelli@stanford.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place