Precision-Based Magnesium Trial

NCT01105169 | Completed Results

• 1 other identifier: 100106
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

Colorectal cancer is the fourth most common incident cancer and the second most common cause of cancer death in the United States, with approximately 150,000 new cases and 57,000 deaths per year. High calcium intake and magnesium may protect against colorectal cancer and adenoma, however, results have been inconsistent. We found that genetic makeup, associated with magnesium absorption and re-absorption, significantly interacted with the calcium and magnesium ratio in relation to the both adenomatous and hyperplastic polyps. Participants who carried at least one 1482Ile allele (G-\>A)of TRPM7 and who consumed diets with a high calcium/magnesium ratio were at a higher risk of adenoma and hyperplastic polyps than were participants who did not carry the polymorphism. We hypothesize that the reduction in the dietary Ca/Mg ratio may change the markers directly related to tumorigenesis. The primary aims of this study are to conduct a randomized placebo-controlled intervention trial to test whether reducing the Ca/mg intake ratio through magnesium supplementation has effects on the related biomarkers. We will also examine whether the effect of modulating Ca/Mg intake ratio may be more pronounced among those who carry the 1482Ile allele compared those who don't carry the 1482Ile allele. Results from our study will help to identify people at a high risk of colorectal adenoma and to develop personalized strategies to prevent occurrence of colorectal adenoma, and thus, colorectal cancer through dietary change or nutritional fortification.

Conditions

Colorectal Cancer

Keywords

Personalized prevention; Colorectal cancer; Investigational Nutrigenetic Studies; Magnesium; Gene polymorphism

Outcome Measures

Primary Outcomes (6)

• TRPM7 Expression Level in Colorectal Mucosa by Mg Treatment Compared With Placebo

  Transient Receptor Potential Melastatin 7 (TRPM7) levels were evaluated quantitatively using a computer-based imaging system composed of an Olympus BX40 Microscope and BioQuant NOVA Prime imaging software (BioQuant). The staining score was computed as "positive cell percentage x reciprocal staining intensity (RSI)", yielding values from 0 to 255, where higher score denoted stronger staining. . Changes (posttreatment-baseline) of TRPM7=log(value at 12 weeks) minus log(value at baseline).

  Baseline to 12 weeks

• COX2 Expression Level in Colorectal Mucosa by Mg Treatment Compared With Placebo

  Cyclooxygenase (COX2) levels were evaluated quantitatively using a computer-based imaging system composed of an Olympus BX40 Microscope and BioQuant NOVA Prime imaging software (BioQuant). The staining score was computed as "positive cell percentage x reciprocal staining intensity (RSI)", yielding values from 0 to 255, where higher score denoted stronger staining. . Changes (posttreatment-baseline) of COX2=log(value at 12 weeks) minus log(value at baseline).

  Baseline to 12 week

• TUNEL Expression in Colorectal Mucosa by Mg Treatment Compared With Placebo

  Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) levels were evaluated quantitatively using a computer-based imaging system composed of an Olympus BX40 Microscope and BioQuant NOVA Prime imaging software (BioQuant) and computed as count of apoptotic cells/mm2 of epithelial cell nuclei area (cells/mm²). Changes (posttreatment-baseline) of TUNEL =log(value at 12 weeks) minus log(value at baseline).

  Baseline to 12 week

• BAX Expression in Colorectal Mucosa by Mg Treatment Compared With Placebo

  BCL2-associated X (BAX) levels were evaluated quantitatively using a computer-based imaging system composed of an Olympus BX40 Microscope and BioQuant NOVA Prime imaging software (BioQuant). The staining score was computed as "positive cell percentage x reciprocal staining intensity (RSI)", yielding values from 0 to 255, where higher score denoted stronger staining. Changes (posttreatment-baseline) of BAX=log(value at 12 weeks) minus log(value at baseline).

  Baseline to 12 week

• pMLKL Expression in Colorectal Mucosa by Mg Treatment Compared With Placebo

  Phosphorylated Mixed Lineage Kinase Like (pMLKL) levels were evaluated quantitatively using a computer-based imaging system composed of an Olympus BX40 Microscope and BioQuant NOVA Prime imaging software (BioQuant). The staining score was computed as "positive cell percentage x reciprocal staining intensity (RSI)", yielding values from 0 to 255, where higher score denoted stronger staining. Changes (posttreatment-baseline) of pMLKL=log(value at 12 weeks) minus log(value at baseline).

  Baseline to 12 week

• Ki67 Expression in Colorectal Mucosa by Mg Treatment Compared With Placebo

  Ki67 levels were evaluated quantitatively using a computer-based imaging system composed of an Olympus BX40 Microscope and BioQuant NOVA Prime imaging software (BioQuant) and calculated as positive nuclei area / epithelial cell nuclei area \* 100 (%). Changes (posttreatment-baseline) of Ki67=log(value at 12 weeks) minus log(value at baseline).

  Baseline to 12 week

Secondary Outcomes (4)

• Serum Magnesium by Mg Treatment Compared With Placebo

  Baseline to 12 week

• Post Treatment Body Magnesium Status by Mg Treatment and Placebo

  At week 12

• Serum C-reactive Protein (CRP) by Mg Treatment Compared With Placebo

  Baseline to 12 week

• Urine Prostaglandin E2 Metabolite (PGE-M) by Mg Treatment Compared With Placebo

  Baseline to 12 week

Study Arms (4)

GG genotype and magnesium treatment

ACTIVE COMPARATOR

Participants who have the GG genotype will be assigned to magnesium glycinate.

Dietary Supplement: Magnesium glycinate

GG genotype and placebo

PLACEBO COMPARATOR

Participants who have the GG genotype will be assigned to placebo group

Dietary Supplement: Placebo

GA/AA genotype and magnesium treatment

ACTIVE COMPARATOR

Participants who have the GA/AA genotype will be assigned to magnesium glycinate

Dietary Supplement: Magnesium glycinate

GA/AA genotype and Placebo

PLACEBO COMPARATOR

Participants who have the GA/AA genotype will be assigned to placebo group

Dietary Supplement: Placebo

Interventions

Placebo DIETARY_SUPPLEMENT

Oral administration of identical-appearing placebo daily for 12 weeks

GA/AA genotype and Placebo; GG genotype and placebo

Magnesium glycinate DIETARY_SUPPLEMENT

Oral administration of magnesium glycinate daily for 12 weeks

GA/AA genotype and magnesium treatment; GG genotype and magnesium treatment

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hyperplastic polyp or/and Adenoma cases
• Polyps free participants with any of the following high risk of colorectal polyps or cancer: (1) family history of colorectal cancer or polyps; (2) current cigarette smoker; (3) obesity (BMI≥30 kg/m2); (4) low intake of fiber (lowest fiber intake quartile: daily intake \<16.6g); (5) high intake of red meat and well-done or processed meat (mutageneity index ≥5852).
• Participants from the TCPS (IRB # 090235), the TIARS (IRB # 090235), from Vanderbilt University Hospital or from other resources
• Consent to be contacted for future studies in TCPS (IRB # 020462), TIARS (IRB#090235)
• Participants with a calcium intake ≥ 700 mg/day measuring with 24 hour dietary recalls
• Participants with a calcium intake \< 2000 mg/day measuring with 24 hour dietary recalls
• Participants with a calcium/magnesium intake ratio \> 2.6
• Participants with known genotype for Thr1482Ile polymorphism in TRPM7
• Will live in Nashville or surrounding area in the next 6 months

You may not qualify if:

• Intolerance to magnesium glycinate or microcrystalline cellulose (placebo)
• Chronic renal diseases and hepatic cirrhosis
• Chronic ischemic heart disease with unstable angina, chronic heart failure at class III or IV and acute myocardial infarction in the last 6 months
• Chronic diarrhea
• Current breastfeeding
• Current or planned pregnancy
• Type I diabetes mellitus
• Pituitary dwarfism
• Use of digoxin and licorice
• Current use of blood anticoagulant drugs such as Dicumarol(Warfarin), Clopidogrel (Plavix), Prasugrel HCl (Efficent), Ticlopidine (Ticlid), Lovenox (Enoxaparin), Fragmin (Dalteparin), Innohep (Tinzaparin), Eptifibatide (Integrilin), Tyrofiban (Aggrastat), and Abciximab (Reopro)
• Current use of lithium carbonate therapy (Eskalith, Lithobid, Lithonate, Lithotabs, Apo-Lithium carbonate, Apo-Lithium carbonate SR, Carbolth, Duralith, PMS-Lithium carbonate, PMS-Lithium citrate)
• Individuals with a history of colon resection or colectomy due to any reason
• Individuals with any history of cancer other than non-melanoma skin cancer
• Individual with history of any organ transplantation
• Individual with a history of gastric bypass due to any reason

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37203, United States

Location

Related Publications (5)

• Sun E, Zhu X, Ness RM, Murff HJ, Sun S, Yu C, Fan L, Azcarate-Peril MA, Shrubsole MJ, Dai Q. Magnesium treatment increases gut microbiome synthesizing vitamin D and inhibiting colorectal cancer: results from a double-blind precision-based randomized placebo-controlled trial. Am J Clin Nutr. 2025 Nov;122(5):1185-1194. doi: 10.1016/j.ajcnut.2025.09.011. Epub 2025 Sep 12.

  PMID: 40946805 DERIVED

• Sun S, Zhu X, Huang X, Yu C, Su T, Murff HJ, Ness RM, Azcarate-Peril MA, Shrubsole MJ, Dai Q. The Association of Gut Microbiota With TRPM7 Genotype, Colorectal Polyps, and Magnesium. J Nutr. 2025 Nov;155(11):3713-3725. doi: 10.1016/j.tjnut.2025.07.015. Epub 2025 Jul 30.

  PMID: 40750038 DERIVED

• 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 DERIVED

• 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 DERIVED

• 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 DERIVED

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

Study Officials

• Qi Dai, MD, PhD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Chang Yu, PhD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Martha J Shrubsole, Ph.D.

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

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: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 14, 2010
• First Posted: April 16, 2010
• Study Start: March 11, 2011
• Primary Completion: December 30, 2024
• Study Completion: July 8, 2025
• Last Updated: February 20, 2026
• Results First Posted: February 20, 2026

Record last verified: 2026-02

Locations

US (1)