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

NCT04196803 | Completed Results

• 4 other identifiers: 100106cR01CA149633R01CA202936R01DK110166
• Study Type: interventional
• Target: 250
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Changes of Cytosine Modification in TMPRSS2 (5-mC at cg16371860) by Magnesium Treatment Versus Placebo

  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 Outcomes (3)

• Changes of Cytosine Modification in TMPRSS2 (5-hmC at cg16371860) by Magnesium Treatment Versus Placebo

  12 Weeks

• Changes of Cytosine Modification in TMPRSS2 (5-mC at cg26337277) by Magnesium Treatment Versus Placebo

  12 Weeks

• Changes of Cytosine Modification in TMPRSS2 (5-hmC at cg26337277) by Magnesium Treatment Versus Placebo

  12 Weeks

Study Arms (2)

magnesium treatment

ACTIVE COMPARATOR

Participants were assigned to magnesium glycinate

Dietary Supplement: Magnesium glycinate

placebo

PLACEBO COMPARATOR

Participants were assigned to placebo group

Dietary Supplement: Placebo

Interventions

Magnesium glycinate DIETARY_SUPPLEMENT

Oral administration of magnesium glycinate daily for 12 weeks

magnesium treatment

Placebo DIETARY_SUPPLEMENT

Oral administration of identical-appearing placebo daily for 12 weeks

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

You may not qualify if:

• \. Participants cannot provide their blood samples in the parent study.

Sponsors & Collaborators

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

Related Publications (5)

• 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.

  PMID: 34116393 BACKGROUND

• 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.

  PMID: 34038556 BACKGROUND

• 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.

  PMID: 32280092 BACKGROUND

• 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.

  PMID: 36223712 BACKGROUND

• 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.

  PMID: 33487303 BACKGROUND

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. Qi Dai
• Organization: Vanderbilt University Medical Center

qi.dai@vanderbilt.edu

615)936-0707

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: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: December 12, 2019
• Study Start: March 11, 2011
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: June 25, 2024
• Results First Posted: June 25, 2024

Record last verified: 2024-06