Ca:Mg Ratio and Cognitive Function

Ca:Mg Ratio and Cognitive Function in the Personalized Prevention of Colorectal Cancer Trial

Between 2000 and 2015, mortality due to Alzheimer's disease (AD) increased by 123%. No drugs have yet been approved to stop or slow the progression of AD. A delay of five years in the expression of AD would reduce the incidence rate by half. Thus, it is critical to develop novel prevention strategies to delay the onset of this common disease.

As an ancillary study conducted within a precision-based randomized trial (R01CA149633; PI, Dai & Yu]"), the investigators reduced Ca:Mg ratios to 2.3 through 3-month personalized Mg supplementation among those who consumed high Ca:Mg ratio diet, but otherwise in good general health. The investigators test the hypothesis that actively reducing the Ca:Mg ratio among those aged >65 years who consume high Ca:Mg ratio diets improves cognitive function compared to the placebo arm. The investigators further conduct molecular epidemiologic studies to understand the molecular mechanisms.

Study Overview

• Status: Completed
• Conditions: Cognitive Function
• Intervention / Treatment: Dietary supplement: Magnesium glycinate; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Participants from our parent study (Personalized Prevention of Colorectal Cancer Trial, NCT#01105169, IRB#100106);
2. Participants who completed the MoCA

Exclusion Criteria:

1. Participants did not 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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: magnesium treatment; Participants will be assigned to magnesium glycinate	Dietary supplement: Magnesium glycinate; Oral administration of magnesium glycinate daily for 12 weeks; Dietary supplement: Placebo; Oral administration of identical-appearing placebo daily for 12 weeks
Placebo Comparator: placebo; Participants will be assigned to placebo group	Dietary supplement: Magnesium glycinate; Oral administration of magnesium glycinate daily for 12 weeks; Dietary supplement: Placebo; Oral administration of identical-appearing placebo daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Score Changes From Baseline by Magnesium Treatment vs. Placebo	Montreal Cognitive Assessment (MoCA) Scoring: The test consists of 30 items, and each item is worth one point, resulting in a maximum score of 30. A higher score indicates better cognitive functioning. The changes of MoCA score=Score at 12 weeks minus Score at baseline.	12 weeks
Overall Score Changes From Baseline by Magnesium Treatment vs. Placebo (Aged ≤65 Years Old)	Montreal Cognitive Assessment (MoCA) Scoring: The test consists of 30 items, and each item is worth one point, resulting in a maximum score of 30. A higher score indicates better cognitive functioning. The changes of MoCA score=Score at 12 weeks minus Score at baseline.	12 weeks
Overall Score Changes From Baseline by Magnesium Treatment vs. Placebo (Aged >65 Years Old)	Montreal Cognitive Assessment (MoCA) Scoring: The test consists of 30 items, and each item is worth one point, resulting in a maximum score of 30. A higher score indicates better cognitive functioning. The changes of MoCA score=Score at 12 weeks minus Score at baseline.	12 weeks
Changes From Baseline of 5-mC Methylation (CpG Sites) in Apolipoprotein E (APOE) by Magnesium Treatment vs. Placebo	5-mC methylation (CpG sites) in Apolipoprotein E (APOE) were measure by TET-assisted bisulfite (TAB)-Array. 5-mC methylation changes=value at 12 weeks minus value at baseline.	12 weeks

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Cancer Institute (NCI)

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.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2012
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: December 10, 2019
• First Submitted That Met QC Criteria: December 10, 2019
• First Posted (Actual): December 12, 2019

Study Record Updates

• Last Update Posted (Actual): May 21, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 100106a; R01CA149633 (U.S. NIH Grant/Contract); R01CA202936 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No