Colorectal Cancer
Conditions
Keywords
Personalized prevention trial, Magnesium, Vitamin D metabolism and synthesis, Magnesium-vitamin D interaction
Brief summary
One striking observation is that a large portion of the inter-person variation in serum 25-hydroxyvitamin D (25(OH)D) levels is unexplained. In vitro and in vivo studies indicate vitamin D synthesizing and metabolizing enzymes are Mg-dependent. Magnesium (Mg) supplementation substantially reversed the resistance to vitamin D treatment in patients with magnesium-dependent vitamin-D-resistant rickets. The investigators reported in 2013 from observational studies conducted in the general US population that Mg intake significantly interacted with vitamin D intake in affecting vitamin D status as well as interacted with serum 25(OH)D in risk of cardiovascular disease mortality and, maybe, colorectal cancer mortality. The potential interaction between Mg and vitamin D was supported by two subsequent studies, including a Finnish cohort study and a mouse study. In the parent study (Personalized Prevention of Colorectal Cancer Trial, NCT01105169), the investigators proposed to measure blood concentration of total 25(OH)D as a secondary aim using Elisa approach. However, following the novel finding of Mg-vitamin D interaction published by the investigators in 2013, they submitted a separate grant application to NCI which was funded in 2014. In the new study, the investigators proposed to use a LC-MS approach, which is more accurate and specific than an Elisa method, to measure 5 vitamin D metabolites. This new ancillary study allows the investigators to evaluate whether Mg supplementation differentially affects vitamin D synthesis and metabolism dependent on baseline serum 25(OH)D levels using existing biospecimens collected in our double-blind placebo-controlled randomized chemoprevention trial.
Interventions
DIETARY_SUPPLEMENTMagnesium glycinate
Oral administration of magnesium glycinate daily for 12 weeks
DIETARY_SUPPLEMENTPlacebo
Oral administration of identical-appearing placebo daily for 12 weeks
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participants from our parent study (Personalized Prevention of Colorectal Cancer Trial, NCT#01105169, IRB#100106); 2. Participants who had completed the above study before the time of the sample selection (October 2015); 3. Participants consent to store/share samples for future research in colorectal tumors.
Exclusion criteria
1\. Participants cannot provide their blood samples in the parent study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparisons of the Changes of Blood 25-Hydroxyvitamin D3 (25(OH)D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | 12 weeks | 25(OH)D3 was extracted from plasma by liquid extraction and measured by using a novel liquid chromatography-mass spectrometry (LC-MS) method. The baseline 25(OH)D were measured by: the baseline value of 25(OH)D2 + the baseline value of 25(OH)D3. The changes of 25(OH)D3 were measured as: the post-treatment value of 25(OH)D3 (at Week 12) - the pre-treatment value of 25(OH)D3 (at baseline). |
| Comparisons of the Changes of Blood 25-Hydroxyvitamin D2 (25(OH)D2) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | 12 weeks | 25(OH)D2 was extracted from plasma by liquid extraction and measured by using a novel liquid chromatography-mass spectrometry (LC-MS) method. The baseline 25(OH)D were measured by: the baseline value of 25(OH)D2 + the baseline value of 25(OH)D3. The changes of 25(OH)D2 were measured as: the post-treatment value of 25(OH)D2 (at Week 12) - the pre-treatment value of 25(OH)D2 (at baseline). |
| Comparisons of the Changes of Blood 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | 12 weeks | 24,25(OH)2D3 was extracted from plasma by liquid extraction and detected by using a novel liquid chromatography-mass spectrometry (LC-MS) method. The baseline 25(OH)D were measured by: the baseline value of 25(OH)D2 + the baseline value of 25(OH)D3. The changes of 24,25(OH)2D3 were measured as: the post-treatment value of 24,25(OH)2D3 (at Week 12) - the pre-treatment value of 24,25(OH)2D3 (at baseline). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Magnesium Glycinate Supplements Participants will be assigned to magnesium glycinate
Magnesium glycinate: Oral administration of magnesium glycinate daily for 12 weeks | 87 |
| Placebo Participants will be assigned to placebo group
Placebo: Oral administration of identical-appearing placebo daily for 12 weeks | 93 |
| Total | 180 |
Baseline characteristics
| Characteristic | Placebo | Total | Magnesium Glycinate Supplements |
|---|---|---|---|
| Age, Continuous | 61.7 years STANDARD_DEVIATION 8.3 | 61.1 years STANDARD_DEVIATION 8.3 | 60.4 years STANDARD_DEVIATION 8.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 92 Participants | 177 Participants | 85 Participants |
| Sex: Female, Male Female | 48 Participants | 90 Participants | 42 Participants |
| Sex: Female, Male Male | 45 Participants | 90 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 87 | 0 / 93 |
| other Total, other adverse events | 0 / 87 | 0 / 93 |
| serious Total, serious adverse events | 0 / 87 | 0 / 93 |
Outcome results
Primary
Comparisons of the Changes of Blood 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels
24,25(OH)2D3 was extracted from plasma by liquid extraction and detected by using a novel liquid chromatography-mass spectrometry (LC-MS) method. The baseline 25(OH)D were measured by: the baseline value of 25(OH)D2 + the baseline value of 25(OH)D3. The changes of 24,25(OH)2D3 were measured as: the post-treatment value of 24,25(OH)2D3 (at Week 12) - the pre-treatment value of 24,25(OH)2D3 (at baseline).
Time frame: 12 weeks
Population: What we include in Rows are not estimates in subgroups, but model-based predictions given specific values of baseline 25-hydroxyvitamin D (25(OH)D) levels. The mean prediction and its standard error are calculated using model coefficient estimates and its variance-covariance matrix, and the sample size is equal to the number of subjects used to fit the model, i.e., overall number of participants analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| The Changes in Magnesium Treatment Arm | Comparisons of the Changes of Blood 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=20 | 4.35 ng/mL | Standard Deviation 0.41 |
| The Changes in Magnesium Treatment Arm | Comparisons of the Changes of Blood 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=30 | 4.31 ng/mL | Standard Deviation 0.32 |
| The Changes in Magnesium Treatment Arm | Comparisons of the Changes of Blood 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=40 | 3.47 ng/mL | Standard Deviation 0.32 |
| The Changes in Magnesium Treatment Arm | Comparisons of the Changes of Blood 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=50 | 2.12 ng/mL | Standard Deviation 0.44 |
| The Changes in Placebo Arm | Comparisons of the Changes of Blood 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=50 | 3.97 ng/mL | Standard Deviation 0.36 |
| The Changes in Placebo Arm | Comparisons of the Changes of Blood 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=20 | 3.96 ng/mL | Standard Deviation 0.39 |
| The Changes in Placebo Arm | Comparisons of the Changes of Blood 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=40 | 3.91 ng/mL | Standard Deviation 0.32 |
| The Changes in Placebo Arm | Comparisons of the Changes of Blood 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=30 | 3.90 ng/mL | Standard Deviation 0.32 |
Primary
Comparisons of the Changes of Blood 25-Hydroxyvitamin D2 (25(OH)D2) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels
25(OH)D2 was extracted from plasma by liquid extraction and measured by using a novel liquid chromatography-mass spectrometry (LC-MS) method. The baseline 25(OH)D were measured by: the baseline value of 25(OH)D2 + the baseline value of 25(OH)D3. The changes of 25(OH)D2 were measured as: the post-treatment value of 25(OH)D2 (at Week 12) - the pre-treatment value of 25(OH)D2 (at baseline).
Time frame: 12 weeks
Population: What we include in Rows are not estimates in subgroups, but model-based predictions given specific values of baseline 25-hydroxyvitamin D (25(OH)D) levels. The mean prediction and its standard error are calculated using model coefficient estimates and its variance-covariance matrix, and the sample size is equal to the number of subjects used to fit the model, i.e., overall number of participants analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| The Changes in Magnesium Treatment Arm | Comparisons of the Changes of Blood 25-Hydroxyvitamin D2 (25(OH)D2) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=20 | -2.22 ng/mL (log-transformed) | Standard Deviation 0.57 |
| The Changes in Magnesium Treatment Arm | Comparisons of the Changes of Blood 25-Hydroxyvitamin D2 (25(OH)D2) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=30 | -1.94 ng/mL (log-transformed) | Standard Deviation 0.45 |
| The Changes in Magnesium Treatment Arm | Comparisons of the Changes of Blood 25-Hydroxyvitamin D2 (25(OH)D2) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=40 | -1.68 ng/mL (log-transformed) | Standard Deviation 0.44 |
| The Changes in Magnesium Treatment Arm | Comparisons of the Changes of Blood 25-Hydroxyvitamin D2 (25(OH)D2) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=50 | -1.43 ng/mL (log-transformed) | Standard Deviation 0.55 |
| The Changes in Placebo Arm | Comparisons of the Changes of Blood 25-Hydroxyvitamin D2 (25(OH)D2) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=50 | -3.56 ng/mL (log-transformed) | Standard Deviation 0.57 |
| The Changes in Placebo Arm | Comparisons of the Changes of Blood 25-Hydroxyvitamin D2 (25(OH)D2) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=20 | -1.65 ng/mL (log-transformed) | Standard Deviation 0.55 |
| The Changes in Placebo Arm | Comparisons of the Changes of Blood 25-Hydroxyvitamin D2 (25(OH)D2) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=40 | -2.13 ng/mL (log-transformed) | Standard Deviation 0.45 |
| The Changes in Placebo Arm | Comparisons of the Changes of Blood 25-Hydroxyvitamin D2 (25(OH)D2) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=30 | -1.38 ng/mL (log-transformed) | Standard Deviation 0.46 |
Primary
Comparisons of the Changes of Blood 25-Hydroxyvitamin D3 (25(OH)D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels
25(OH)D3 was extracted from plasma by liquid extraction and measured by using a novel liquid chromatography-mass spectrometry (LC-MS) method. The baseline 25(OH)D were measured by: the baseline value of 25(OH)D2 + the baseline value of 25(OH)D3. The changes of 25(OH)D3 were measured as: the post-treatment value of 25(OH)D3 (at Week 12) - the pre-treatment value of 25(OH)D3 (at baseline).
Time frame: 12 weeks
Population: What we include in Rows are not estimates in subgroups, but model-based predictions given specific values of baseline 25-hydroxyvitamin D (25(OH)D) levels. The mean prediction and its standard error are calculated using model coefficient estimates and its variance-covariance matrix, and the sample size is equal to the number of subjects used to fit the model, i.e., overall number of participants analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| The Changes in Magnesium Treatment Arm | Comparisons of the Changes of Blood 25-Hydroxyvitamin D3 (25(OH)D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=30 | 32.20 ng/mL | Standard Error 1.56 |
| The Changes in Magnesium Treatment Arm | Comparisons of the Changes of Blood 25-Hydroxyvitamin D3 (25(OH)D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=20 | 30.95 ng/mL | Standard Error 2.18 |
| The Changes in Magnesium Treatment Arm | Comparisons of the Changes of Blood 25-Hydroxyvitamin D3 (25(OH)D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=40 | 29.76 ng/mL | Standard Error 1.84 |
| The Changes in Magnesium Treatment Arm | Comparisons of the Changes of Blood 25-Hydroxyvitamin D3 (25(OH)D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=50 | 24.89 ng/mL | Standard Error 2.74 |
| The Changes in Placebo Arm | Comparisons of the Changes of Blood 25-Hydroxyvitamin D3 (25(OH)D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=50 | 31.76 ng/mL | Standard Error 2 |
| The Changes in Placebo Arm | Comparisons of the Changes of Blood 25-Hydroxyvitamin D3 (25(OH)D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=30 | 29.41 ng/mL | Standard Error 1.61 |
| The Changes in Placebo Arm | Comparisons of the Changes of Blood 25-Hydroxyvitamin D3 (25(OH)D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=40 | 30.31 ng/mL | Standard Error 1.8 |
| The Changes in Placebo Arm | Comparisons of the Changes of Blood 25-Hydroxyvitamin D3 (25(OH)D3) Between Magnesium Treatment and Placebo Arm, Stratified by the Baseline 25-hydroxyvitamin D (25(OH)D) Levels | Baseline 25(OH)D=20 | 29.37 ng/mL | Standard Error 2.08 |