Calcium: Magnesium Balance, Microbiota, and Necroptosis and Inflammation

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).

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Dietary supplement: Magnesium glycinate; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Martha Shrubsole, PhD, Vanderbilt University

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2017
• Primary Completion (Actual): February 28, 2024
• Study Completion (Actual): March 28, 2024

Study Registration Dates

• First Submitted: January 12, 2020
• First Submitted That Met QC Criteria: January 12, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: 100106d

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No