Calcium: Magnesium Balance, Microbiota, and Necroptosis and Inflammation

Transient receptor potential melastatin 7 (TRPM7), a magnesium (Mg) -regulated chanzyme possessing both ion channel and kinase activities, has a much stronger affinity to Mg2+ than calcium (Ca)2+. We previously reported that individuals with the TRPM7 GA/AA genotype and consumed diets high in Ca:Mg ratio had an increased risk of colorectal polyps. The TRPM7 gene was also observed to possess "driver" mutations that contribute to developing multiple cancers. However, the molecular mechanism remains unclear.

To identify if the gut microbiota plays a role in this association, we will investigate whether optimizing Ca:Mg intake ratios to 2.3 altered the abundance of the microbes (e.g. associated with TRPM7 genotype and the risk of metachronous polyps) at the genus level in at least one sample type among stool, swab and tissue in a double-blind 2x2 factorial (TRPM7 genotype and Ca:Mg ratios) randomized trial (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): 250
• 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
Comparisons of the Changes of Genera Prevotella by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples	changes=value at 12 weeks minus value at baseline. Difference between post-treatment and baseline, means increase or reduced the abundance of genera Prevotella in the test samples (rectal mucosa or rectal swab or stool).	12 weeks
Comparisons of the Changes of Genera Bacteroides by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples	changes=value at 12 weeks minus value at baseline. Difference between post-treatment and baseline, means increase or reduced the abundance of genera Prevotella in the test samples (rectal mucosa or rectal swab or stool).	12 weeks

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Cancer Institute (NCI); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• 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): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 3, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: 100106d; R01CA149633 (U.S. NIH Grant/Contract); R01DK110166 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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