Methylomic Biomarkers for Magnesium Deficiency in the Personalized Prevention of Colorectal Cancer Trial

Methylomic Biomarkers for Magnesium Deficiency and Colon Neoplasia Prevention

Based on the magnesium (Mg) tolerance test, the "gold standard" test of Mg status, more than 50% US participants had Mg deficiency. Observations suggest that the associations between high Mg intake and disease risks may completely differ by the underlying Mg status. Due to major limitations, the Mg tolerance test is not used in conventional clinical practice and rarely used in research. Instead, serum Mg is used for clinical diagnosis. However, serum Mg performs very poorly at identifying those with Mg deficiency. There is a great need to develop implementable, sensitive, and specific biomarkers which can be easily used for identifying people with Mg deficiency.

It is known that DNA methylation changes are inducible by environmental exposures, including nutrients, and reversible when the exposure disappears. We propose to identify 5-hmC/5-mC biomarkers for Mg deficiency by a 4- phase EWAS study in the "Personalized Prevention of Colorectal Cancer Trial [PPCCT, R01CA149633; PI, Dai & Yu]" with a total of 240 participants. Mg tolerance test will be used as the gold standard. Finally, using newly identified biomarkers, we will evaluate if 12-week Mg treatment reduces TRPM7 expression, essential in Mg homeostasis and colorectal carcinogenesis, in rectal tissues only among those with Mg deficiency.

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Participants from our parent study (Personalized Prevention of Colorectal Cancer Trial, NCT#01105169, IRB#100106);
2. Participants consent to store/share biospecimens for future research.

Exclusion Criteria:

1. Participants cannot provide their blood samples 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
5-mC and 5-hmC assays	DNA was extract from WBC samples and measured by using TAB-Seq & TAB-Array protocol	12 Weeks
Serum magnesium		12 Weeks
Plasma methionine cycle metabolites	Plasma SAM, SAH, homocysteine and methionine measured by stable-isotope dilution liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS)	12 Weeks

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: December 10, 2019
• First Submitted That Met QC Criteria: December 10, 2019
• First Posted (Actual): December 12, 2019

Study Record Updates

• Last Update Posted (Actual): August 2, 2023
• Last Update Submitted That Met QC Criteria: August 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Nutrition Disorders; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Deficiency Diseases; Malnutrition; Colorectal Neoplasms; Magnesium Deficiency
• Other Study ID Numbers: 100106c

Drug and device information, study documents

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