Calcium: Magnesium Balance, Microbiota, and Necroptosis and Inflammation

Study Overview
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Brief Summary
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In addition to microbiota-host interaction on inflammatory response, many enzymes, including three enzymes critical in gluconeogenesis and transport of amino acids and carbohydrates in energy metabolism, are dependent on the Ca/Mg ratio, indicating critical roles of the Ca/Mg ratio in carbohydrate fermentation and energy metabolism in bacteria. In pilot metagenomic study conducted by the investigators, they found all the significantly changed biologic functions within the microbial community caused by a reduction in the Ca/Mg ratio are biologically dependent on the Ca/Mg ratio or Mg. It is striking that the functions with significant changes in stool samples were centered on the fermentation of carbohydrates and energy metabolism while the functions in rectal swabs were related to immune response. Tissue also had a distinct profile from stool and swab. These findings have very broad clinical and public health significance for many inflammation-related diseases or metabolic disorders. Due to the small sample size in the pilot study, the investigators plan to confirm these findings using the biospecimens collected in the parent study (Personalized Prevention of Colorectal Cancer Trial, NCT01105169).

Official Title
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Calcium: Magnesium Balance, Microbiota, and Necroptosis and Inflammation

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 the parent study (Personalized Prevention of Colorectal Cancer Trial, NCT#01105169, IRB#100106) Exclusion Criteria: • Participants did not provide any stool/swab/rectal biopsy sample 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 |
| --- | --- | --- |
| Quantitative PCR for Bifidobacterium and Lactobacillus | Conduct high-throughput quantitative PCR for Bifidobacterium and Lactobacillus in stool, rectal swab, and rectal mucosa samples | 12 weeks | 
| Immunohistochemistry for necroptosis-related biomarkers | Conduct immunohistochemistry for necroptosis-related biomarkers in rectal mucosa samples | 12 weeks | 
| Conduct metagenomic analysis of stool, rectal swab, and rectal mucosa samples |  | 12 weeks |