search
Back to results

Precision-Based Magnesium Trial

Primary Purpose

Colorectal Cancer

Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Magnesium glycinate
Placebo
Sponsored by
Vanderbilt University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Colorectal Cancer focused on measuring Personalized prevention, Colorectal cancer, Investigational Nutrigenetic Studies, Magnesium, Gene polymorphism

Eligibility Criteria

40 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Arm Label

GG genotype and magnesium treatment

GG genotype and placebo

GA/AA genotype and magnesium treatment

GA/AA genotype and Placebo

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

The protein expression levels of TRPM7, MLKL in colorectal mucosa
TRPM7 and MLKL have been detected using immunohistochemical (IHC) techniques.
Ratios of Ki67:BAX, Ki67:TUNEL in rectal epithelial
Ki67:BAX and Ki67:TUNEL have been analyzed using immunohistochemical (IHC) techniques.
Expression of Cox2 in rectal epithelia
Cox2 has been analyzed using immunohistochemical (IHC)

Secondary Outcome Measures

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.
Post treatment body magnesium status
Body magnesium status obtained using magnesium tolerance test (MTT)
Circulation 25-Hydroxyvitamin D
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
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.

Full Information

First Posted
April 14, 2010
Last Updated
June 26, 2023
Sponsor
Vanderbilt University Medical Center
search

1. Study Identification

Unique Protocol Identification Number
NCT01105169
Brief Title
Precision-Based Magnesium Trial
Official Title
Personalized Prevention of Colorectal Cancer Trial (PPCCT)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 2010 (undefined)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center

4. Oversight

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
Personalized prevention, Colorectal cancer, Investigational Nutrigenetic Studies, Magnesium, Gene polymorphism

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
265 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GG genotype and magnesium treatment
Arm Type
Active Comparator
Arm Description
Participants who have the GG genotype will be assigned to magnesium glycinate.
Arm Title
GG genotype and placebo
Arm Type
Placebo Comparator
Arm Description
Participants who have the GG genotype will be assigned to placebo group
Arm Title
GA/AA genotype and magnesium treatment
Arm Type
Active Comparator
Arm Description
Participants who have the GA/AA genotype will be assigned to magnesium glycinate
Arm Title
GA/AA genotype and Placebo
Arm Type
Placebo Comparator
Arm Description
Participants who have the GA/AA genotype will be assigned to placebo group
Intervention Type
Dietary Supplement
Intervention Name(s)
Magnesium glycinate
Intervention Description
Oral administration of magnesium glycinate daily for 12 weeks
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Oral administration of identical-appearing placebo daily for 12 weeks
Primary Outcome Measure Information:
Title
The protein expression levels of TRPM7, MLKL in colorectal mucosa
Description
TRPM7 and MLKL have been detected using immunohistochemical (IHC) techniques.
Time Frame
12 week (rectal biopsies will be collected at the baseline and the end of the intervention)
Title
Ratios of Ki67:BAX, Ki67:TUNEL in rectal epithelial
Description
Ki67:BAX and Ki67:TUNEL have been analyzed using immunohistochemical (IHC) techniques.
Time Frame
12 week (rectal biopsies will be collected at the baseline and the end of the intervention)
Title
Expression of Cox2 in rectal epithelia
Description
Cox2 has been analyzed using immunohistochemical (IHC)
Time Frame
12 week (rectal biopsies will be collected at the baseline and the end of the intervention)
Secondary Outcome Measure Information:
Title
Serum magnesium
Description
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.
Time Frame
12 week
Title
Post treatment body magnesium status
Description
Body magnesium status obtained using magnesium tolerance test (MTT)
Time Frame
12 week after treatment
Title
Circulation 25-Hydroxyvitamin D
Time Frame
12 week
Title
Serum C-reactive protein concentration
Description
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
Time Frame
12 week
Title
Urine excretion of prostaglandin E2 metabolite (PGE-M)
Description
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.
Time Frame
12 week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qi Dai, MD, PhD
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Chang Yu, PhD
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Martha J Shrubsole, Ph.D.
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
34038556
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.
Results Reference
derived
PubMed Identifier
33487303
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.
Results Reference
derived

Learn more about this trial

Precision-Based Magnesium Trial

We'll reach out to this number within 24 hrs