Ancillary Study of Methylation Biomarkers in a Randomized Controlled Trial of a Personalized Prevention of Colorectal Cancer
Methylomic Biomarkers, Magnesium Deficiency and Colon Neoplasia Prevention
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Participants from our parent study (Personalized Prevention of Colorectal Cancer Trial, NCT#01105169, IRB#100106);
- 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: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: magnesium treatment
Participants were assigned to magnesium glycinate
|
Oral administration of magnesium glycinate daily for 12 weeks
|
|
Placebo Comparator: placebo
Participants were assigned to placebo group
|
Oral administration of identical-appearing placebo daily for 12 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Changes of Cytosine Modification in TMPRSS2 (5-mC at cg16371860) by Magnesium Treatment Versus Placebo
Time Frame: 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. |
12 Weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Changes of Cytosine Modification in TMPRSS2 (5-hmC at cg16371860) by Magnesium Treatment Versus Placebo
Time Frame: 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. |
12 Weeks
|
|
Changes of Cytosine Modification in TMPRSS2 (5-mC at cg26337277) by Magnesium Treatment Versus Placebo
Time Frame: 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. |
12 Weeks
|
|
Changes of Cytosine Modification in TMPRSS2 (5-hmC at cg26337277) by Magnesium Treatment Versus Placebo
Time Frame: 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. |
12 Weeks
|
Collaborators and Investigators
Publications and helpful links
General Publications
- Zhu X, Borenstein AR, Zheng Y, Zhang W, Seidner DL, Ness R, Murff HJ, Li B, Shrubsole MJ, Yu C, Hou L, Dai Q. Ca:Mg Ratio, APOE Cytosine Modifications, and Cognitive Function: Results from a Randomized Trial. J Alzheimers Dis. 2020;75(1):85-98. doi: 10.3233/JAD-191223.
- Fan L, Zhu X, Zheng Y, Zhang W, Seidner DL, Ness R, Murff HJ, Yu C, Huang X, Shrubsole MJ, Hou L, Dai Q. Magnesium treatment on methylation changes of transmembrane serine protease 2 (TMPRSS2). Nutrition. 2021 Sep;89:111340. doi: 10.1016/j.nut.2021.111340. Epub 2021 May 7.
- Fan L, Zhu X, Rosanoff A, Costello RB, Yu C, Ness R, Seidner DL, Murff HJ, Roumie CL, Shrubsole MJ, Dai Q. Magnesium Depletion Score (MDS) Predicts Risk of Systemic Inflammation and Cardiovascular Mortality among US Adults. J Nutr. 2021 Aug 7;151(8):2226-2235. doi: 10.1093/jn/nxab138.
- Fan L, Zhu X, Sun S, Yu C, Huang X, Ness R, Dugan LL, Shu L, Seidner DL, Murff HJ, Fodor AA, Azcarate-Peril MA, Shrubsole MJ, Dai Q. Ca:Mg ratio, medium-chain fatty acids, and the gut microbiome. Clin Nutr. 2022 Nov;41(11):2490-2499. doi: 10.1016/j.clnu.2022.08.031. Epub 2022 Sep 12.
- Fan L, Yu D, Zhu X, Huang X, Murff HJ, Azcarate-Peril MA, Shrubsole MJ, Dai Q. Magnesium and imidazole propionate. Clin Nutr ESPEN. 2021 Feb;41:436-438. doi: 10.1016/j.clnesp.2020.12.011. Epub 2021 Jan 7.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 100106c
- R01CA149633 (U.S. NIH Grant/Contract)
- R01CA202936 (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
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.