Precision-Based Magnesium Trial

• ClinicalTrials.gov Identifier: NCT01105169
• Recruitment Status: Active, not recruiting
• First Posted: April 16, 2010
• Last Update Posted: July 14, 2022
• Sponsor: Vanderbilt University Medical Center
• Information provided by (Responsible Party): Qi Dai, Vanderbilt University Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer	Dietary Supplement: Magnesium glycinate; Dietary Supplement: Placebo	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 250 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Personalized Prevention of Colorectal Cancer Trial
• Study Start Date: August 2010
• Estimated Primary Completion Date: July 2023
• Estimated Study Completion Date: July 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: GG genotype and magnesium treatment; Participants who have the GG genotype will be assigned to magnesium glycinate.	Dietary Supplement: Magnesium glycinate; Oral administration of magnesium glycinate daily for 12 weeks
Placebo Comparator: GG genotype and placebo; Participants who have the GG genotype will be assigned to placebo group	Dietary Supplement: Placebo; Oral administration of identical-appearing placebo daily for 12 weeks
Active Comparator: GA/AA genotype and magnesium treatment; Participants who have the GA/AA genotype will be assigned to magnesium glycinate	Dietary Supplement: Magnesium glycinate; Oral administration of magnesium glycinate daily for 12 weeks
Placebo Comparator: GA/AA genotype and Placebo; Participants who have the GA/AA genotype will be assigned to placebo group	Dietary Supplement: Placebo; Oral administration of identical-appearing placebo daily for 12 weeks

Outcome Measures

Primary Outcome Measures :

1. The protein expression levels of TRPM7, MLKL in colorectal mucosa [ Time Frame: 12 week (rectal biopsies will be collected at the baseline and the end of the intervention) ]
   TRPM7 and MLKL have been detected using immunohistochemical (IHC) techniques.
2. Ratios of Ki67:BAX, Ki67:TUNEL in rectal epithelial [ Time Frame: 12 week (rectal biopsies will be collected at the baseline and the end of the intervention) ]
   Ki67:BAX and Ki67:TUNEL have been analyzed using immunohistochemical (IHC) techniques.
3. Expression of Cox2 in rectal epithelia [ Time Frame: 12 week (rectal biopsies will be collected at the baseline and the end of the intervention) ]
   Cox2 has been analyzed using immunohistochemical (IHC)

Secondary Outcome Measures :

1. Serum magnesium [ Time Frame: 12 week ]
   Serum magnesium concentration was determined using 7D70 Magnesium Reagent Kit from Abbot Laboratories (Abbott Park, IL) the assay was conducted at the Vanderbilt Pathology Laboratory Services.
2. Post treatment body magnesium status [ Time Frame: 12 week after treatment ]
   Body magnesium status obtained using magnesium tolerance test (MTT)
3. Circulation 25-Hydroxyvitamin D [ Time Frame: 12 week ]
4. Serum C-reactive protein concentration [ Time Frame: 12 week ]
   Assays of CRP for 180 participants were performed using immuno turbidimetric immunoassay based commercial assay kits (Pointe Scientific, Inc, Canton, MI) at Vanderbilt Lipid Laboratory
5. Urine excretion of prostaglandin E2 metabolite (PGE-M) [ Time Frame: 12 week ]
   Urinary PGE-M level was measured using a liquid chromatography/tandem mass spectrometric method at the Integrated Health Sciences Facility Core of the Vanderbilt Center in Molecular Toxicology.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37203

Sponsors and Collaborators

Vanderbilt University Medical Center

Investigators

• Principal Investigator: 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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Qi Dai, Professor, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT01105169
• Other Study ID Numbers: 100106
• First Posted: April 16, 2010
• Last Update Posted: July 14, 2022
• Last Verified: July 2022

Keywords provided by Qi Dai, Vanderbilt University Medical Center:

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

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases