Colorectal CancerNCT04196803
Ancillary Study of Methylation Biomarkers in a Randomized Controlled Trial of a Personalized Prevention of Colorectal Cancer
A study testing Magnesium glycinate in people with Colorectal Cancer, run by Vanderbilt University Medical Center.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Magnesium glycinate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 250 participants
- Where
- No sites listed yet
- Study dates
- 11 Mar 2011to 30 Jun 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participants from our parent study (Personalized Prevention of Colorectal Cancer Trial, NCT#01105169, IRB#100106);
- Participants consent to store/share biospecimens for future research.
Who cannot join
- 1. Participants cannot provide their blood samples in the parent study.
About this study
Official title: 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.
- Conditions
- Colorectal Cancer
- Being tested
- Magnesium glycinate, Placebo
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnesium glycinateDietary supplement
Oral administration of magnesium glycinate daily for 12 weeks
PlaceboDietary supplement
Oral administration of identical-appearing placebo daily for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| magnesium treatment | Active comparator | Participants were assigned to magnesium glycinate Receives: Dietary Supplement: Magnesium glycinate |
| placebo | Placebo comparator | Participants were assigned to placebo group Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 Weeks
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2019
- Study start11 Mar 2011
- Primary completion30 Jun 2023
- Study completion30 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 250 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Principal investigator, Qi Dai, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04196803
- Sponsor's protocol ID
- 100106c
- Other IDs
- R01CA149633, R01CA202936, R01DK110166
- Status last verified
- Jun 2024
- First submitted
- 10 Dec 2019
- Last updated
- 25 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 34116393Fan 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.
PubMed 34038556Zhu 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.
PubMed 32280092Fan 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.
PubMed 36223712Fan 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.
PubMed 33487303
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Methylomic Biomarkers, Magnesium Deficiency and Colon Neoplasia Prevention
- ClinicalTrials.gov ID
- NCT04196803
- Acronym / sponsor ID
- 100106c
- Conditions
- Colorectal Cancer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 250 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 11 Mar 2011 (actual)
- Primary completion
- 30 Jun 2023 (actual)
- Study completion
- 30 Jun 2023 (actual)
- First posted
- 12 Dec 2019 (actual)
- Results
- Posted 25 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| magnesium treatment | Active comparator | Dietary Supplement: Magnesium glycinateParticipants were assigned to magnesium glycinate |
| placebo | Placebo comparator | Dietary Supplement: PlaceboParticipants were assigned to placebo group |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Participants from our parent study (Personalized Prevention of Colorectal Cancer Trial, NCT#01105169, IRB#100106);
- Participants consent to store/share biospecimens for future research.
Key exclusion criteria (1 listed)
- 1. Participants cannot provide their blood samples in the parent study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Magnesium glycinateOral administration of magnesium glycinate daily for 12 weeks | Dietary supplement | magnesium treatment |
| PlaceboOral administration of identical-appearing placebo daily for 12 weeks | Dietary supplement | placebo |
Primary outcome
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.
3 secondary outcomes
Changes of Cytosine Modification in TMPRSS2 (5-hmC at cg16371860) by Magnesium Treatment Versus Placebo
Time frame: 12 Weeks
Changes of Cytosine Modification in TMPRSS2 (5-mC at cg26337277) by Magnesium Treatment Versus Placebo
Time frame: 12 Weeks
Changes of Cytosine Modification in TMPRSS2 (5-hmC at cg26337277) by Magnesium Treatment Versus Placebo
Time frame: 12 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 34116393Fan 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.
- Background: PubMed 34038556Fan 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.
- Background: PubMed 32280092Zhu 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.
- Background: PubMed 36223712Fan 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.
- Background: PubMed 33487303Fan 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Magnesium glycinate in people with Colorectal Cancer, run by Vanderbilt University Medical Center.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes of Cytosine Modification in TMPRSS2 (5-mC at cg16371860) by Magnesium Treatment Versus Placebo (time frame: 12 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04196803, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2024.