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CompletedNCT03265483Updated Aug 23, 2024Results posted

Magnesium Treatment on Vitamin D Metabolism in Participants Completed Personalized Prevention of Colorectal Cancer Trial

An interventional study of Magnesium glycinate and Placebo in Colorectal Cancer, sponsored by Vanderbilt University Medical Center. Completed at 1 site in United States. Open to participants aged 40 Years to 85 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-08-23.

Sponsored by Vanderbilt University Medical Center · Not applicable, Interventional, and Prevention

Phase
Not applicable
Study type
Interventional
Enrollment
180
Allocation
Randomized
Ages
40 Years to 85 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Colorectal Cancer

Keywords

  • Personalized prevention trial
  • Magnesium
  • Vitamin D metabolism and synthesis
  • Magnesium-vitamin D interaction
03

Who can participate

Ages eligible
40 Years to 85 Years
Sexes eligible
All
Accepts 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

Exclusion Criteria:

  1. Participants cannot provide their blood samples in the parent study.
04

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
180 participants (actual)

Study arms

  • Active comparator
    Magnesium treatment

    Participants will be assigned to magnesium glycinate

    Dietary Supplement: Magnesium glycinate

  • Placebo comparator
    Placebo

    Participants will be assigned to placebo group

    Dietary Supplement: Placebo

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

05

What researchers measure

Primary outcomes

  1. 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

  2. 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

  3. 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

06

Results

Posted Aug 23, 2024

Participant flow

Participant flow — Overall Study
MilestoneMagnesium Glycinate SupplementsPlacebo
Started8793
Completed8793
Not completed00

Outcome measures

PrimaryComparisons 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
Reported as:
Mean · ng/mL
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
ng/mLThe Changes in Magnesium Treatment ArmThe Changes in Placebo Arm
Baseline 25(OH)D=3032.20 ± 1.5629.41 ± 1.61
Baseline 25(OH)D=2030.95 ± 2.1829.37 ± 2.08
Baseline 25(OH)D=4029.76 ± 1.8430.31 ± 1.80
Baseline 25(OH)D=5024.89 ± 2.7431.76 ± 2.00
PrimaryComparisons 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
Reported as:
Mean · ng/mL (log-transformed)
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
ng/mL (log-transformed)The Changes in Magnesium Treatment ArmThe Changes in Placebo Arm
Baseline 25(OH)D=20-2.22 ± 0.57-1.65 ± 0.55
Baseline 25(OH)D=30-1.94 ± 0.45-1.38 ± 0.46
Baseline 25(OH)D=40-1.68 ± 0.44-2.13 ± 0.45
Baseline 25(OH)D=50-1.43 ± 0.55-3.56 ± 0.57
PrimaryComparisons 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
Reported as:
Mean · ng/mL
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
ng/mLThe Changes in Magnesium Treatment ArmThe Changes in Placebo Arm
Baseline 25(OH)D=204.35 ± 0.413.96 ± 0.39
Baseline 25(OH)D=304.31 ± 0.323.90 ± 0.32
Baseline 25(OH)D=403.47 ± 0.323.91 ± 0.32
Baseline 25(OH)D=502.12 ± 0.443.97 ± 0.36

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Magnesium Supplements0/87 (0%)0/87 (0%)0/87 (0%)
Placebo0/93 (0%)0/93 (0%)0/93 (0%)

Baseline characteristics

This is an NCI-funded ancillary study nested in the parent study (registered at clinicaltrials.gov as NCT01105169). For the current study, 180 participants who had completed the parent study by October 2015 were selected, including 87 participants in the treatment arm and 93 in the placebo arm. Based on the proposal, we compared the vitamin D metabolites between the two arms (magnesium treatment vs placebo).

Age, Continuous
Age, Continuous(years)Magnesium Glycinate SupplementsPlaceboTotal
Mean60.4 ± 8.361.7 ± 8.361.1 ± 8.3
Sex: Female, Male
Sex: Female, Male(Participants)Magnesium Glycinate SupplementsPlaceboTotal
Female424890
Male454590
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Magnesium Glycinate SupplementsPlaceboTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American213
White8592177
More than one race000
Unknown or Not Reported000
07

Study locations

1 site
  • Vanderbilt University Medical Center
    Nashville, Tennessee 37203, United States
08

References and documents

Publications

  • Zhu X, Borenstein AR, Zheng Y, Zhang W, Seidner DL, Ness R, Murff HJ, Li B, Shrubsole MJ, Yu C, Hou L, Dai Q. Ca:Mg Ratio, APOE Cytosine Modifications, and Cognitive Function: Results from a Randomized Trial. J Alzheimers Dis. 2020;75(1):85-98. doi: 10.3233/JAD-191223. PubMed 32280092 ↗
  • Dai Q, Zhu X, Manson JE, Song Y, Li X, Franke AA, Costello RB, Rosanoff A, Nian H, Fan L, Murff H, Ness RM, Seidner DL, Yu C, Shrubsole MJ. Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial. Am J Clin Nutr. 2018 Dec 1;108(6):1249-1258. doi: 10.1093/ajcn/nqy274. PubMed 30541089 ↗
09

Registry details

Key details

Study ID
NCT03265483
Lead sponsor
Vanderbilt University Medical Center
Responsible party
Martha Shrubsole (Research rofessor, Vanderbilt University Medical Center) — Principal investigator
First posted
Aug 29, 2017
Start date
Sep 2014
Primary completion
Aug 2016
Completion
Aug 2016
Results posted
Aug 23, 2024
Last update
Aug 23, 2024

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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