Colorectal Cancer
Conditions
Brief summary
Transient receptor potential melastatin 7 (TRPM7), a magnesium (Mg) -regulated chanzyme possessing both ion channel and kinase activities, has a much stronger affinity to Mg2+ than calcium (Ca)2+. We previously reported that individuals with the TRPM7 GA/AA genotype and consumed diets high in Ca:Mg ratio had an increased risk of colorectal polyps. The TRPM7 gene was also observed to possess driver mutations that contribute to developing multiple cancers. However, the molecular mechanism remains unclear. To identify if the gut microbiota plays a role in this association, we will investigate whether optimizing Ca:Mg intake ratios to 2.3 altered the abundance of the microbes (e.g. associated with TRPM7 genotype and the risk of metachronous polyps) at the genus level in at least one sample type among stool, swab and tissue in a double-blind 2x2 factorial (TRPM7 genotype and Ca:Mg ratios) randomized trial (Personalized Prevention of Colorectal Cancer Trial, NCT01105169).
Interventions
DIETARY_SUPPLEMENTMagnesium glycinate
Oral administration of magnesium glycinate daily for 12 weeks
DIETARY_SUPPLEMENTPlacebo
Oral administration of identical-appearing placebo daily for 12 weeks
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Cancer Institute (NCI)
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
• Participants from the parent study (Personalized Prevention of Colorectal Cancer Trial, NCT#01105169, IRB#100106)
Exclusion criteria
• Participants did not provide any stool/swab/rectal biopsy sample in the parent study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparisons of the Changes of Genera Prevotella by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | 12 weeks | changes=value at 12 weeks minus value at baseline. Difference between post-treatment and baseline, means increase or reduced the abundance of genera Prevotella in the test samples (rectal mucosa or rectal swab or stool). |
| Comparisons of the Changes of Genera Bacteroides by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | 12 weeks | changes=value at 12 weeks minus value at baseline. Difference between post-treatment and baseline, means increase or reduced the abundance of genera Prevotella in the test samples (rectal mucosa or rectal swab or stool). |
Countries
United States
Participant flow
Recruitment details
Participants, aged 40-85 y, with colorectal polyp or polyp-free individuals with high risk of colorectal cancer and had a calcium intake of ≥700 and \<2000 mg/d, and their calcium-to-magnesium intake ratio was \>2.6 (based on baseline two 24-hour dietary recalls) and have blood samples were recruited from Vanderbilt patient sources from March 11, 2011 to Jan 30, 2016 .
Participants by arm
| Arm | Count |
|---|---|
| GG Genotype and Magnesium Treatment Participants who have the GG genotype will be assigned to magnesium glycinate
Magnesium glycinate: Oral administration of magnesium glycinate daily for 12 weeks | 76 |
| GG Genotype and Placebo Participants who have the GG genotype will be assigned to placebo group
Placebo: Oral administration of identical-appearing placebo daily for 12 weeks | 75 |
| GA/AA Genotype and Magnesium Treatment Participants who have the GA/AA genotype will be assigned to magnesium glycinate
Magnesium glycinate: Oral administration of magnesium glycinate daily for 12 weeks | 43 |
| GA/AA Genotype and Placebo Participants who have the GA/AA genotype will be assigned to placebo group
Placebo: Oral administration of identical-appearing placebo daily for 12 weeks | 45 |
| Total | 239 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 3 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 1 | 1 |
Baseline characteristics
| Characteristic | GG Genotype and Placebo | GA/AA Genotype and Magnesium Treatment | GA/AA Genotype and Placebo | GG Genotype and Magnesium Treatment | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 23 Participants | 14 Participants | 19 Participants | 23 Participants | 79 Participants |
| Age, Categorical Between 18 and 65 years | 52 Participants | 29 Participants | 26 Participants | 53 Participants | 160 Participants |
| Age, Continuous | 60.0 years STANDARD_DEVIATION 8.5 | 60.0 years STANDARD_DEVIATION 7 | 61.4 years STANDARD_DEVIATION 7.6 | 60.2 years STANDARD_DEVIATION 8.2 | 60.7 years STANDARD_DEVIATION 7.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 74 Participants | 43 Participants | 45 Participants | 74 Participants | 236 Participants |
| Region of Enrollment United States | 75 participants | 43 participants | 45 participants | 76 participants | 239 participants |
| Sex: Female, Male Female | 35 Participants | 23 Participants | 23 Participants | 32 Participants | 113 Participants |
| Sex: Female, Male Male | 40 Participants | 20 Participants | 22 Participants | 44 Participants | 126 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 78 | 0 / 47 | 0 / 48 |
| other Total, other adverse events | 1 / 77 | 2 / 78 | 3 / 47 | 1 / 48 |
| serious Total, serious adverse events | 0 / 77 | 0 / 78 | 0 / 47 | 0 / 48 |
Outcome results
Primary
Comparisons of the Changes of Genera Bacteroides by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples
changes=value at 12 weeks minus value at baseline. Difference between post-treatment and baseline, means increase or reduced the abundance of genera Prevotella in the test samples (rectal mucosa or rectal swab or stool).
Time frame: 12 weeks
Population: Among participants with with rectal mucosa and rectal swab and stool samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GG Genotype and Magnesium Treatment | Comparisons of the Changes of Genera Bacteroides by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Rectal mucosa | -0.030 percentage of sample | Standard Error 0.205 |
| GG Genotype and Magnesium Treatment | Comparisons of the Changes of Genera Bacteroides by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Stool | -0.063 percentage of sample | Standard Error 0.536 |
| GG Genotype and Magnesium Treatment | Comparisons of the Changes of Genera Bacteroides by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Rectal swab | 0.024 percentage of sample | Standard Error 0.413 |
| GG Genotype and Placebo | Comparisons of the Changes of Genera Bacteroides by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Rectal mucosa | -0.027 percentage of sample | Standard Error 0.252 |
| GG Genotype and Placebo | Comparisons of the Changes of Genera Bacteroides by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Stool | 0.022 percentage of sample | Standard Error 0.41 |
| GG Genotype and Placebo | Comparisons of the Changes of Genera Bacteroides by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Rectal swab | -0.013 percentage of sample | Standard Error 0.465 |
| GA/AA Genotype and Magnesium Treatment | Comparisons of the Changes of Genera Bacteroides by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Rectal swab | -0.041 percentage of sample | Standard Error 0.355 |
| GA/AA Genotype and Magnesium Treatment | Comparisons of the Changes of Genera Bacteroides by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Rectal mucosa | 0.039 percentage of sample | Standard Error 0.208 |
| GA/AA Genotype and Magnesium Treatment | Comparisons of the Changes of Genera Bacteroides by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Stool | -0.105 percentage of sample | Standard Error 0.377 |
| GA/AA Genotype and Placebo | Comparisons of the Changes of Genera Bacteroides by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Rectal mucosa | -0.025 percentage of sample | Standard Error 0.196 |
| GA/AA Genotype and Placebo | Comparisons of the Changes of Genera Bacteroides by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Stool | 0.084 percentage of sample | Standard Error 0.418 |
| GA/AA Genotype and Placebo | Comparisons of the Changes of Genera Bacteroides by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Rectal swab | -0.017 percentage of sample | Standard Error 0.283 |
Comparison: 1. GG genotype and magnesium treatment vs GG genotype and placebo;~2. GA/AA genotype and magnesium treatment vs GA/AA genotype and Placebop-value: <0.05Regression, Linear
Primary
Comparisons of the Changes of Genera Prevotella by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples
changes=value at 12 weeks minus value at baseline. Difference between post-treatment and baseline, means increase or reduced the abundance of genera Prevotella in the test samples (rectal mucosa or rectal swab or stool).
Time frame: 12 weeks
Population: Among participants with with rectal mucosa and rectal swab and stool samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GG Genotype and Magnesium Treatment | Comparisons of the Changes of Genera Prevotella by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Rectal Mucosa | 0.108 percentage of sample | Standard Error 2.268 |
| GG Genotype and Magnesium Treatment | Comparisons of the Changes of Genera Prevotella by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Stool | -0.059 percentage of sample | Standard Error 1.716 |
| GG Genotype and Magnesium Treatment | Comparisons of the Changes of Genera Prevotella by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Rectal Swab | -0.174 percentage of sample | Standard Error 1.954 |
| GG Genotype and Placebo | Comparisons of the Changes of Genera Prevotella by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Rectal Mucosa | 0.245 percentage of sample | Standard Error 2.686 |
| GG Genotype and Placebo | Comparisons of the Changes of Genera Prevotella by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Stool | -0.001 percentage of sample | Standard Error 1.814 |
| GG Genotype and Placebo | Comparisons of the Changes of Genera Prevotella by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Rectal Swab | -0.095 percentage of sample | Standard Error 2.239 |
| GA/AA Genotype and Magnesium Treatment | Comparisons of the Changes of Genera Prevotella by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Rectal Swab | -0.919 percentage of sample | Standard Error 2.165 |
| GA/AA Genotype and Magnesium Treatment | Comparisons of the Changes of Genera Prevotella by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Rectal Mucosa | -0.076 percentage of sample | Standard Error 2.355 |
| GA/AA Genotype and Magnesium Treatment | Comparisons of the Changes of Genera Prevotella by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Stool | 0.363 percentage of sample | Standard Error 1.276 |
| GA/AA Genotype and Placebo | Comparisons of the Changes of Genera Prevotella by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Rectal Mucosa | 0.132 percentage of sample | Standard Error 2.034 |
| GA/AA Genotype and Placebo | Comparisons of the Changes of Genera Prevotella by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Stool | 0.137 percentage of sample | Standard Error 1.639 |
| GA/AA Genotype and Placebo | Comparisons of the Changes of Genera Prevotella by Mg Treatment vs. Placebo in Rectal Mucosa, Swab and Stool Samples | Rectal Swab | 0.364 percentage of sample | Standard Error 2.111 |
Comparison: 1. GG genotype and magnesium treatment vs GG genotype and placebo;~2. GA/AA genotype and magnesium treatment vs GA/AA genotype and Placebo.p-value: <0.05Regression, Linear