Precision-Based Magnesium Trial

Colorectal Cancer Clinical Trial

Official title:

Personalized Prevention of Colorectal Cancer Trial (PPCCT)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01105169
• Other study ID #: 100106
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 2010
• Est. completion date: July 2024

Study information

• Verified date: June 2023
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 265
• Est. completion date: July 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Dietary Supplement:
• Magnesium glycinate
Oral administration of magnesium glycinate daily for 12 weeks
• Placebo
Oral administration of identical-appearing placebo daily for 12 weeks

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The protein expression levels of TRPM7, MLKL in colorectal mucosa	TRPM7 and MLKL have been detected using immunohistochemical (IHC) techniques.	12 week (rectal biopsies will be collected at the baseline and the end of the intervention)
Primary	Ratios of Ki67:BAX, Ki67:TUNEL in rectal epithelial	Ki67:BAX and Ki67:TUNEL have been analyzed using immunohistochemical (IHC) techniques.	12 week (rectal biopsies will be collected at the baseline and the end of the intervention)
Primary	Expression of Cox2 in rectal epithelia	Cox2 has been analyzed using immunohistochemical (IHC)	12 week (rectal biopsies will be collected at the baseline and the end of the intervention)
Secondary	Serum magnesium	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.	12 week
Secondary	Post treatment body magnesium status	Body magnesium status obtained using magnesium tolerance test (MTT)	12 week after treatment
Secondary	Circulation 25-Hydroxyvitamin D		12 week
Secondary	Serum C-reactive protein concentration	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	12 week
Secondary	Urine excretion of prostaglandin E2 metabolite (PGE-M)	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.	12 week