Precision-Based Magnesium Trial

Vanderbilt University Medical Center250 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

250

Conditions

Colorectal Cancer

Eligibility

Sex: ALLMin age: 40 YearsMax age: 85 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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 * Individuals with Inflammatory bowel disease * Individuals if creatinine clearance is \< 50 * Currently institutionalized * Homeless individual (address, telephone etc.) * Unable to provide informed consent * Any condition that in the opinion of the investigator raises concerns about protocol compliance

Outcomes

Primary Outcomes

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).

Time frame: 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).