Personalized Prevention of Colorectal Cancer Trial (PPCCT)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 250
- 试验地点
- 1
- 主要终点
- TRPM7 Expression Level in Colorectal Mucosa by Mg Treatment Compared With Placebo
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
GG genotype and magnesium treatment
Participants who have the GG genotype will be assigned to magnesium glycinate.
干预措施: Magnesium glycinate (Dietary Supplement)
GG genotype and placebo
Participants who have the GG genotype will be assigned to placebo group
干预措施: Placebo (Dietary Supplement)
GA/AA genotype and magnesium treatment
Participants who have the GA/AA genotype will be assigned to magnesium glycinate
干预措施: Magnesium glycinate (Dietary Supplement)
GA/AA genotype and Placebo
Participants who have the GA/AA genotype will be assigned to placebo group
干预措施: Placebo (Dietary Supplement)
结局指标
主要结局
TRPM7 Expression Level in Colorectal Mucosa by Mg Treatment Compared With Placebo
时间窗: Baseline to 12 weeks
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).
COX2 Expression Level in Colorectal Mucosa by Mg Treatment Compared With Placebo
时间窗: Baseline to 12 week
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).
TUNEL Expression in Colorectal Mucosa by Mg Treatment Compared With Placebo
时间窗: Baseline to 12 week
Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) levels were evaluated quantitatively using a computer-based imaging system composed of an Olympus BX40 Microscope and BioQuant NOVA Prime imaging software (BioQuant) and computed as count of apoptotic cells/mm2 of epithelial cell nuclei area (cells/mm²). Changes (posttreatment-baseline) of TUNEL =log(value at 12 weeks) minus log(value at baseline).
BAX Expression in Colorectal Mucosa by Mg Treatment Compared With Placebo
时间窗: Baseline to 12 week
BCL2-associated X (BAX) 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 BAX=log(value at 12 weeks) minus log(value at baseline).
pMLKL Expression in Colorectal Mucosa by Mg Treatment Compared With Placebo
时间窗: Baseline to 12 week
Phosphorylated Mixed Lineage Kinase Like (pMLKL) 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 pMLKL=log(value at 12 weeks) minus log(value at baseline).
Ki67 Expression in Colorectal Mucosa by Mg Treatment Compared With Placebo
时间窗: Baseline to 12 week
Ki67 levels were evaluated quantitatively using a computer-based imaging system composed of an Olympus BX40 Microscope and BioQuant NOVA Prime imaging software (BioQuant) and calculated as positive nuclei area / epithelial cell nuclei area \* 100 (%). Changes (posttreatment-baseline) of Ki67=log(value at 12 weeks) minus log(value at baseline).
次要结局
- Serum C-reactive protein concentration(12 week)
- Serum magnesium(12 week)
- Post treatment body magnesium status(12 week after treatment)
- Circulation 25-Hydroxyvitamin D(12 week)
- Serum Magnesium by Mg Treatment Compared With Placebo(Baseline to 12 week)
- Post Treatment Body Magnesium Status by Mg Treatment and Placebo(At week 12)
- Serum C-reactive Protein (CRP) by Mg Treatment Compared With Placebo(Baseline to 12 week)
- Urine Prostaglandin E2 Metabolite (PGE-M) by Mg Treatment Compared With Placebo(Baseline to 12 week)
研究者
Qi Dai
Professor
Vanderbilt University Medical Center