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| ID | Type | Description | Link |
|---|---|---|---|
| R01CA149633 | U.S. NIH Grant/Contract | View source | |
| R01CA202936 | U.S. NIH Grant/Contract | View source | |
| R01DK110166 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| magnesium treatment | Active Comparator | Participants were assigned to magnesium glycinate |
|
| placebo | Placebo Comparator | Participants were assigned to placebo group |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Magnesium glycinate | Dietary Supplement | Oral administration of magnesium glycinate daily for 12 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Changes of Cytosine Modification in TMPRSS2 (5-hmC at cg16371860) by Magnesium Treatment Versus Placebo | 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 |
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Inclusion Criteria:
Exclusion Criteria:
1. Participants cannot provide their blood samples in the parent study.
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34116393 | Background | 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. | |
| 34038556 | 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. |
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Participants, aged 40-85 y, with colorectal polyp or polyp-free individuals with high risk of colorectal cancer and had a calcium intake of ≥700 and <2000 mg/d, and their calcium-to-magnesium intake ratio was >2.6 (based on baseline two 24-hour dietary recalls) and have blood samples were recruited from Vanderbilt patient sources from March 11, 2011 to Jan 30, 2016 .
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| ID | Title | Description |
|---|---|---|
| FG000 | Magnesium Treatment | Participants were assigned to magnesium glycinate Magnesium glycinate: Oral administration of magnesium glycinate daily for 12 weeks |
| FG001 | Placebo | Participants were assigned to placebo group Placebo: Oral administration of identical-appearing placebo daily for 12 weeks |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Magnesium Treatment | Participants were assigned to magnesium glycinate Magnesium glycinate: Oral administration of magnesium glycinate daily for 12 weeks |
| BG001 | Placebo | Participants were assigned to placebo group Placebo: Oral administration of identical-appearing placebo daily for 12 weeks |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Overall analysis and stratified analysis by age (<65 years, ≥ 65 years) | Posted | Mean | Standard Deviation | units on CpG sites | 12 Weeks |
|
In the 12 weeks trial, we conducted safety and compliance calls to collect adverse event data.
The definition of adverse event and/or serious adverse event is from the clinicaltrials.gov Definitions.
We conducted safety and compliance calls to collect adverse event data.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Magnesium Treatment | Participants were assigned to magnesium glycinate Magnesium glycinate: Oral administration of magnesium glycinate daily for 12 weeks |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment | abdominal pain, stomach hurt |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Qi Dai | Vanderbilt University Medical Center | 615)936-0707 | qi.dai@vanderbilt.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 8, 2022 | May 28, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| C091418 | magnesium diglycinate |
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| Placebo | Dietary Supplement | Oral administration of identical-appearing placebo daily for 12 weeks |
|
| Changes of Cytosine Modification in TMPRSS2 (5-mC at cg26337277) by Magnesium Treatment Versus Placebo | 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 | 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 |
| 32280092 | 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. |
| 36223712 | 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. |
| 33487303 | 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. |
| Lost to Follow-up |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Participants were assigned to placebo group
Placebo: Oral administration of identical-appearing placebo daily for 12 weeks
|
|
|
| Secondary | Changes of Cytosine Modification in TMPRSS2 (5-hmC at cg16371860) by Magnesium Treatment Versus Placebo | 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. | Overall analysis and stratified analysis by age (<65 years, ≥ 65 years) | Posted | Mean | Standard Deviation | units on CpG sites | 12 Weeks |
|
|
|
|
| Secondary | Changes of Cytosine Modification in TMPRSS2 (5-mC at cg26337277) by Magnesium Treatment Versus Placebo | 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. | Overall analysis and stratified analysis by age (<65 years, ≥ 65 years) | Posted | Mean | Standard Deviation | units on CpG sites | 12 Weeks |
|
|
|
|
| Secondary | Changes of Cytosine Modification in TMPRSS2 (5-hmC at cg26337277) by Magnesium Treatment Versus Placebo | 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. | Overall analysis and stratified analysis by age (<65 years, ≥ 65 years) | Posted | Mean | Standard Deviation | units on CpG sites | 12 Weeks |
|
|
|
|
| 0 |
| 124 |
| 0 |
| 124 |
| 4 |
| 124 |
| EG001 | Placebo | Participants were assigned to placebo group Placebo: Oral administration of identical-appearing placebo daily for 12 weeks | 0 | 126 | 0 | 126 | 3 | 126 |
|
| Bleeding after the rectal biopsy procedure | Gastrointestinal disorders | Systematic Assessment |
|
| Feel sick | General disorders | Systematic Assessment |
|
| Arthritic pain in fingers | General disorders | Systematic Assessment |
|
| Weight gain | General disorders | Systematic Assessment | 10 pound weight gain |
|
| Interaction with blood pressure medication | Vascular disorders | Systematic Assessment | may be having an adverse effect on blood pressure medication |
|
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| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| Age<65 |
|
|
| Age≥65 |
|
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| Age<65 |
|
|
| Age≥65 |
|
|
| Age<65 |
|
|
| Age≥65 |
|
|