Clinical trial NCT01105169: Precision-Based Magnesium Trial
Official title: Personalized Prevention of Colorectal Cancer Trial (PPCCT)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Colorectal Cancer
Keywords: Personalized prevention
Colorectal cancer
Investigational Nutrigenetic Studies
Magnesium
Gene polymorphism
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2010-04-16
Enrollment: 265
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

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.


Eligibility 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

Primary outcomes:
measure: The protein expression levels of TRPM7, MLKL in colorectal mucosa
timeFrame: 12 week (rectal biopsies will be collected at the baseline and the end of the intervention)
measure: Ratios of Ki67:BAX, Ki67:TUNEL in rectal epithelial
timeFrame: 12 week (rectal biopsies will be collected at the baseline and the end of the intervention)
measure: Expression of Cox2 in rectal epithelia
timeFrame: 12 week (rectal biopsies will be collected at the baseline and the end of the intervention)
Secondary outcomes:
measure: Serum magnesium
timeFrame: 12 week
measure: Post treatment body magnesium status
timeFrame: 12 week after treatment
measure: Circulation 25-Hydroxyvitamin D
timeFrame: 12 week
measure: Serum C-reactive protein concentration
timeFrame: 12 week
measure: Urine excretion of prostaglandin E2 metabolite (PGE-M)
timeFrame: 12 week
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Qi Dai, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University Medical Center
name: Chang Yu, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University Medical Center
name: Martha J Shrubsole, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.