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

Study Overview
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Brief Summary
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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.

Official Title
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Effect of Magnesium Treatment on Vitamin D Resistance

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Dietary Supplement: Magnesium glycinate
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants from our parent study (Personalized Prevention of Colorectal Cancer Trial, NCT#01105169, IRB#100106); Participants who had completed the above study before the time of the sample selection (October 2015); 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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GG genotype and magnesium treatment<br>Participants who have the GG genotype will be assigned to magnesium glycinate | Dietary Supplement: Magnesium glycinate<br>* Oral administration of magnesium glycinate daily for 12 weeks<br>|
| Placebo Comparator: GG genotype and placebo<br>Participants who have the GG genotype will be assigned to placebo group | Dietary Supplement: Placebo<br>* Oral administration of identical-appearing placebo daily for 12 weeks<br>|
| Active Comparator: GA/AA genotype and magnesium treatment<br>Participants who have the GA/AA genotype will be assigned to magnesium glycinate | Dietary Supplement: Magnesium glycinate<br>* Oral administration of magnesium glycinate daily for 12 weeks<br>|
| Placebo Comparator: GA/AA genotype and Placebo<br>Participants who have the GA/AA genotype will be assigned to placebo group | Dietary Supplement: Placebo<br>* Oral administration of identical-appearing placebo daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood 25-Hydroxyvitamin D3 | 25-Hydroxyvitamin D3 was extracted from plasma by liquid extraction and measured by using a novel liquid chromatography-mass spectrometry (LC-MS) method. | 12 weeks | 
| Blood 25-Hydroxyvitamin D2 | 25-Hydroxyvitamin D3 was extracted from plasma by liquid extraction, and measured by using a novel liquid chromatography-mass spectrometry (LC-MS) method | 12 weeks | 
| Blood 24,25-Dihydroxycholecalciferol (24,25-dihydroxyvitamin D3) | 24,25-dihydroxyvitamin D3 was extracted from plasma by liquid extraction, and detected by using a novel liquid chromatography-mass spectrometry (LC-MS) method. | 12 weeks | 
| Blood 1,25-dihydroxyvitamin D3 | 1,25-dihydroxyvitamin D3 was extracted from plasma using ALPCO immunoextraction kit following manufacturer's protocols. It was detected by a liquid chromatography-mass spectrometry (LC-MS) method. | 12 weeks | 
| Blood 1,25-dihydroxyvitamin D2 | 1,25-dihydroxyvitamin D2 were extracted from plasma using ALPCO immunoextraction kit following manufacturer's protocols. It was detected by a liquid chromatography-mass spectrometry (LC-MS) method. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Personalized prevention trial, Magnesium, Vitamin D metabolism and synthesis, Magnesium-vitamin D interaction