Calcium: Magnesium Balance, Microbiota, and Necroptosis and Inflammation

NCT04229992 | Completed Results

• 3 other identifiers: 100106dR01DK110166R01CA149633
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (4)

GG genotype and magnesium treatment

ACTIVE COMPARATOR

Participants who have the GG genotype will be assigned to magnesium glycinate

Dietary Supplement: Magnesium glycinate

GG genotype and placebo

PLACEBO COMPARATOR

Participants who have the GG genotype will be assigned to placebo group

Dietary Supplement: Placebo

GA/AA genotype and magnesium treatment

ACTIVE COMPARATOR

Participants who have the GA/AA genotype will be assigned to magnesium glycinate

Dietary Supplement: Magnesium glycinate

GA/AA genotype and Placebo

PLACEBO COMPARATOR

Participants who have the GA/AA genotype will be assigned to placebo group

Dietary Supplement: Placebo

Interventions

Magnesium glycinate DIETARY_SUPPLEMENT

Oral administration of magnesium glycinate daily for 12 weeks

GA/AA genotype and magnesium treatment; GG genotype and magnesium treatment

Placebo DIETARY_SUPPLEMENT

Oral administration of identical-appearing placebo daily for 12 weeks

GA/AA genotype and Placebo; GG genotype and placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants from the parent study (Personalized Prevention of Colorectal Cancer Trial, NCT#01105169, IRB#100106)

You may not qualify if:

• Participants did not provide any stool/swab/rectal biopsy sample in the parent study

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37203, United States

Location

Related Publications (1)

• Sun E, Zhu X, Ness RM, Murff HJ, Sun S, Yu C, Fan L, Azcarate-Peril MA, Shrubsole MJ, Dai Q. Magnesium treatment increases gut microbiome synthesizing vitamin D and inhibiting colorectal cancer: results from a double-blind precision-based randomized placebo-controlled trial. Am J Clin Nutr. 2025 Nov;122(5):1185-1194. doi: 10.1016/j.ajcnut.2025.09.011. Epub 2025 Sep 12.

  PMID: 40946805 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

magnesium diglycinate

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Dr. Martha Shrubsole, Dr. Qi Dai
• Organization: Vanderbilt University Medical Center

Martha.shrubsole@vanderbilt.edu, qi.dai@vanderbilt.edu

(615)936-0707

Study Officials

• Martha Shrubsole, PhD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Professor

Study Record Dates

• First Submitted: January 12, 2020
• First Posted: January 18, 2020
• Study Start: May 5, 2017
• Primary Completion: February 28, 2024
• Study Completion: March 28, 2024
• Last Updated: January 28, 2025
• Results First Posted: January 28, 2025

Record last verified: 2025-01

Locations

US (1)