<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03265483</url>
  </required_header>
  <id_info>
    <org_study_id>100106b</org_study_id>
    <nct_id>NCT03265483</nct_id>
  </id_info>
  <brief_title>Magnesium Treatment on Vitamin D Metabolism in Participants Completed Personalized Prevention of Colorectal Cancer Trial</brief_title>
  <official_title>Effect of Magnesium Treatment on Vitamin D Resistance</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      One striking observation is that a large portion of the inter-person variation in serum&#xD;
      25-hydroxyvitamin D (25(OH)D) levels is unexplained. In vitro and in vivo studies indicate&#xD;
      vitamin D synthesizing and metabolizing enzymes are Mg-dependent. Magnesium (Mg)&#xD;
      supplementation substantially reversed the resistance to vitamin D treatment in patients with&#xD;
      magnesium-dependent vitamin-D-resistant rickets. The investigators reported in 2013 from&#xD;
      observational studies conducted in the general US population that Mg intake significantly&#xD;
      interacted with vitamin D intake in affecting vitamin D status as well as interacted with&#xD;
      serum 25(OH)D in risk of cardiovascular disease mortality and, maybe, colorectal cancer&#xD;
      mortality. The potential interaction between Mg and vitamin D was supported by two subsequent&#xD;
      studies, including a Finnish cohort study and a mouse study.&#xD;
&#xD;
      In the parent study (Personalized Prevention of Colorectal Cancer Trial, NCT01105169), the&#xD;
      investigators proposed to measure blood concentration of total 25(OH)D as a secondary aim&#xD;
      using Elisa approach. However, following the novel finding of Mg-vitamin D interaction&#xD;
      published by the investigators in 2013, they submitted a separate grant application to NCI&#xD;
      which was funded in 2014. In the new study, the investigators proposed to use a LC-MS&#xD;
      approach, which is more accurate and specific than an Elisa method, to measure 5 vitamin D&#xD;
      metabolites. This new ancillary study allows the investigators to evaluate whether Mg&#xD;
      supplementation differentially affects vitamin D synthesis and metabolism dependent on&#xD;
      baseline serum 25(OH)D levels using existing biospecimens collected in our double-blind&#xD;
      placebo-controlled randomized chemoprevention trial.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">August 2016</completion_date>
  <primary_completion_date type="Actual">August 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Blood 25-Hydroxyvitamin D3</measure>
    <time_frame>12 weeks</time_frame>
    <description>25-Hydroxyvitamin D3 was extracted from plasma by liquid extraction and measured by using a novel liquid chromatography-mass spectrometry (LC-MS) method.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood 25-Hydroxyvitamin D2</measure>
    <time_frame>12 weeks</time_frame>
    <description>25-Hydroxyvitamin D3 was extracted from plasma by liquid extraction, and measured by using a novel liquid chromatography-mass spectrometry (LC-MS) method</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood 24,25-Dihydroxycholecalciferol (24,25-dihydroxyvitamin D3)</measure>
    <time_frame>12 weeks</time_frame>
    <description>24,25-dihydroxyvitamin D3 was extracted from plasma by liquid extraction, and detected by using a novel liquid chromatography-mass spectrometry (LC-MS) method.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood 1,25-dihydroxyvitamin D3</measure>
    <time_frame>12 weeks</time_frame>
    <description>1,25-dihydroxyvitamin D3 was extracted from plasma using ALPCO immunoextraction kit following manufacturer's protocols. It was detected by a liquid chromatography-mass spectrometry (LC-MS) method.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood 1,25-dihydroxyvitamin D2</measure>
    <time_frame>12 weeks</time_frame>
    <description>1,25-dihydroxyvitamin D2 were extracted from plasma using ALPCO immunoextraction kit following manufacturer's protocols. It was detected by a liquid chromatography-mass spectrometry (LC-MS) method.</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">180</enrollment>
  <condition>Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>GG genotype and magnesium treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants who have the GG genotype will be assigned to magnesium glycinate</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GG genotype and placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants who have the GG genotype will be assigned to placebo group</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GA/AA genotype and magnesium treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants who have the GA/AA genotype will be assigned to magnesium glycinate</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GA/AA genotype and Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants who have the GA/AA genotype will be assigned to placebo group</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Magnesium glycinate</intervention_name>
    <description>Oral administration of magnesium glycinate daily for 12 weeks</description>
    <arm_group_label>GA/AA genotype and magnesium treatment</arm_group_label>
    <arm_group_label>GG genotype and magnesium treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral administration of identical-appearing placebo daily for 12 weeks</description>
    <arm_group_label>GA/AA genotype and Placebo</arm_group_label>
    <arm_group_label>GG genotype and placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Participants from our parent study (Personalized Prevention of Colorectal Cancer&#xD;
             Trial, NCT#01105169, IRB#100106);&#xD;
&#xD;
          2. Participants who had completed the above study before the time of the sample selection&#xD;
             (October 2015);&#xD;
&#xD;
          3. Participants consent to store/share samples for future research in colorectal tumors.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Participants cannot provide their blood samples in the parent study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 25, 2017</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>August 28, 2017</last_update_submitted>
  <last_update_submitted_qc>August 28, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University Medical Center</investigator_affiliation>
    <investigator_full_name>Martha Shrubsole</investigator_full_name>
    <investigator_title>Research Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Personalized prevention trial</keyword>
  <keyword>Magnesium</keyword>
  <keyword>Vitamin D metabolism and synthesis</keyword>
  <keyword>Magnesium-vitamin D interaction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>November 7, 2022</submitted>
    <returned>September 14, 2023</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03265483
org study id: 100106b
nct id: NCT03265483
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
One striking observation is that a large portion of the inter-person variation in serum
      25-hydroxyvitamin D (25(OH)D) levels is unexplained. In vitro and in vivo studies indicate
      vitamin D synthesizing and metabolizing enzymes are Mg-dependent. Magnesium (Mg)
      supplementation substantially reversed the resistance to vitamin D treatment in patients with
      magnesium-dependent vitamin-D-resistant rickets. The investigators reported in 2013 from
      observational studies conducted in the general US population that Mg intake significantly
      interacted with vitamin D intake in affecting vitamin D status as well as interacted with
      serum 25(OH)D in risk of cardiovascular disease mortality and, maybe, colorectal cancer
      mortality. The potential interaction between Mg and vitamin D was supported by two subsequent
      studies, including a Finnish cohort study and a mouse study.

      In the parent study (Personalized Prevention of Colorectal Cancer Trial, NCT01105169), the
      investigators proposed to measure blood concentration of total 25(OH)D as a secondary aim
      using Elisa approach. However, following the novel finding of Mg-vitamin D interaction
      published by the investigators in 2013, they submitted a separate grant application to NCI
      which was funded in 2014. In the new study, the investigators proposed to use a LC-MS
      approach, which is more accurate and specific than an Elisa method, to measure 5 vitamin D
      metabolites. This new ancillary study allows the investigators to evaluate whether Mg
      supplementation differentially affects vitamin D synthesis and metabolism dependent on
      baseline serum 25(OH)D levels using existing biospecimens collected in our double-blind
      placebo-controlled randomized chemoprevention trial.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Blood 25-Hydroxyvitamin D3
time frame: 12 weeks
description: 25-Hydroxyvitamin D3 was extracted from plasma by liquid extraction and measured by using a novel liquid chromatography-mass spectrometry (LC-MS) method.
measure: Blood 25-Hydroxyvitamin D2
time frame: 12 weeks
description: 25-Hydroxyvitamin D3 was extracted from plasma by liquid extraction, and measured by using a novel liquid chromatography-mass spectrometry (LC-MS) method
measure: Blood 24,25-Dihydroxycholecalciferol (24,25-dihydroxyvitamin D3)
time frame: 12 weeks
description: 24,25-dihydroxyvitamin D3 was extracted from plasma by liquid extraction, and detected by using a novel liquid chromatography-mass spectrometry (LC-MS) method.
measure: Blood 1,25-dihydroxyvitamin D3
time frame: 12 weeks
description: 1,25-dihydroxyvitamin D3 was extracted from plasma using ALPCO immunoextraction kit following manufacturer's protocols. It was detected by a liquid chromatography-mass spectrometry (LC-MS) method.
measure: Blood 1,25-dihydroxyvitamin D2
time frame: 12 weeks
description: 1,25-dihydroxyvitamin D2 were extracted from plasma using ALPCO immunoextraction kit following manufacturer's protocols. It was detected by a liquid chromatography-mass spectrometry (LC-MS) method.
arm group label: GG genotype and magnesium treatment
arm group type: Active Comparator
description: Participants who have the GG genotype will be assigned to magnesium glycinate
arm group label: GG genotype and placebo
arm group type: Placebo Comparator
description: Participants who have the GG genotype will be assigned to placebo group
arm group label: GA/AA genotype and magnesium treatment
arm group type: Active Comparator
description: Participants who have the GA/AA genotype will be assigned to magnesium glycinate
arm group label: GA/AA genotype and Placebo
arm group type: Placebo Comparator
description: Participants who have the GA/AA genotype will be assigned to placebo group
intervention type: Dietary Supplement
intervention name: Magnesium glycinate
description: Oral administration of magnesium glycinate daily for 12 weeks
arm group label: GA/AA genotype and magnesium treatment
arm group label: GG genotype and magnesium treatment
intervention type: Dietary Supplement
intervention name: Placebo
description: Oral administration of identical-appearing placebo daily for 12 weeks
arm group label: GA/AA genotype and Placebo
arm group label: GG genotype and placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University Medical Center
investigator full name: Martha Shrubsole
investigator title: Research Associate Professor
mesh term: Colorectal Neoplasms
submitted: November 7, 2022
returned: September 14, 2023