Ancillary Study of Methylation Biomarkers in a Randomized Controlled Trial of a Personalized Prevention of Colorectal Cancer

Not Applicable

Completed

• Conditions: Colorectal Cancer
• Interventions: Dietary Supplement: Placebo; Dietary Supplement: Magnesium glycinate

• Registration Number: NCT04196803
• Lead Sponsor: Vanderbilt University Medical Center

Brief Summary

Based on the magnesium tolerance test (MTT, "gold standard" for assessing magnesium (Mg) status), it was found that over 50% of participants in the US exhibited Mg deficiency. Studies suggest that the relationship between high Mg intake and disease risks may be varied by an individual's Mg status. Despite its importance, MTT is not commonly employed in routine clinical practice or research studies. Instead, serum Mg levels are typically used for clinical diagnosis, although this method has shown limited efficacy in identifying Mg deficiency accurately. Consequently, there is a pressing need to develop practical, sensitive, and specific biomarkers that can efficiently identify individuals with Mg deficiency.

It is known that DNA methylation changes are inducible by environmental exposures, including nutrients, and reversible when the exposure disappears. There are two major types of DNA methylation modifications, 5-hydroxymethylcytosine (5-hmC) and 5-methylcytosine (5-mC). 5-mC is often associated with suppressed gene expression. 5-hmC, generated by the oxidation of 5-mC, is specifically enriched in expressed genes and play a critical role in activating and/or maintaining gene expression. We plan identify 5-hmC and 5-mC for Mg deficiency by a 4- phase comprehensive epigenome-wide association study (EWAS) using the samples collected in the "Personalized Prevention of Colorectal Cancer Trial \[PPCCT, R01CA149633; PI, Dai \& Yu\]" .

The parent trial \[NCT04196023\] that supports this ancillary research is a randomized controlled trial to evaluate the efficacy of reducing the Ca:Mg ratio among those who consume high Ca:Mg ratio diets to decrease the risk of colorectal cancer. For this ancillary trial research, the investigators are examining ancillary measures of Changes of Cytosine Modification in TMPRSS2.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study Start: 2011-03-11
• Study First Submitted: 2019-12-10
• Study First Submitted QC: 2019-12-10
• Study First Posted: 2019-12-12
• Primary Completion: 2023-06-30
• Study Completion: 2023-06-30
• Results First Submitted: 2024-04-09
• Status Verified: 2024-06
• Results First Submitted QC: 2024-06-21
• Last Update Submitted: 2024-06-21
• Results First Posted: 2024-06-25
• Last Update Posted: 2024-06-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 250

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.

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Exclusion Criteria

1. Participants cannot provide their blood samples in the parent study.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	Participants were assigned to placebo group
magnesium treatment	Magnesium glycinate	Participants were assigned to magnesium glycinate

Primary Outcome Measures

Name	Time	Method
Changes of Cytosine Modification in TMPRSS2 (5-mC at cg16371860) by Magnesium Treatment Versus Placebo	12 Weeks	Increases in 5-mC methylation at cg16371860 (the promoter) indicate a hindered process of transcription initiation and, subsequently, lower levels of TMPRSS2 expression.; 5-mC methylation changes=value at 12 weeks minus value at baseline.

Secondary Outcome Measures

Name	Time	Method
Changes of Cytosine Modification in TMPRSS2 (5-hmC at cg16371860) by Magnesium Treatment Versus Placebo	12 Weeks	Decreases in 5-hmC methylation at cg16371860 (the promoter) indicate a hindered process of transcription initiation and, subsequently, lower levels of TMPRSS2 expression.; 5-hmC methylation changes=value at 12 weeks minus value at baseline.
Changes of Cytosine Modification in TMPRSS2 (5-mC at cg26337277) by Magnesium Treatment Versus Placebo	12 Weeks	Increases in 5-mC methylation at cg26337277 (the promoter) indicate a hindered process of transcription initiation and, subsequently, lower levels of TMPRSS2 expression.; 5-mC methylation changes=value at 12 weeks minus value at baseline.
Changes of Cytosine Modification in TMPRSS2 (5-hmC at cg26337277) by Magnesium Treatment Versus Placebo	12 Weeks	Decreases in 5-hmC methylation at cg26337277 (the promoter) indicate a hindered process of transcription initiation and, subsequently, lower levels of TMPRSS2 expression.; 5-hmC methylation changes=value at 12 weeks minus value at baseline.