<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/NCT02986490</url>
  </required_header>
  <id_info>
    <org_study_id>UF 9362</org_study_id>
    <secondary_id>2014-A00381-46</secondary_id>
    <nct_id>NCT02986490</nct_id>
  </id_info>
  <brief_title>Magnesium Variations and Cardiometabolic Risk in Patients With Antipsychotic Drugs</brief_title>
  <official_title>Influence of Magnesium Variations (Serum and Intra-erythrocyte) on Markers of Cardiometabolic Risk in Long-term Prescription of Antipsychotic Drugs: a Prospective Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Montpellier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Montpellier</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: Antipsychotics can induce metabolic disorders such as obesity, hyperglycemia,&#xD;
      dyslipidemia or metabolic syndrome. It has been observed that treatment with antipsychotic&#xD;
      could be accompanied by a decrease in the concentration of serum magnesium. Low serum&#xD;
      concentrations of magnesium are potentially a risk factor of cardiac sudden death (Peacock,&#xD;
      2010). Hypotheses linking magnesium and pathogenesis of cardiovacuscular diseases are&#xD;
      multiple. Also, it seems to exist a close relationship between magnesium and carbohydrate&#xD;
      metabolism. Most studies on the subject have generally studied plasmatic magnesium.&#xD;
&#xD;
      Objective : Describe the relationship between changes in serum and intra-erythrocyte&#xD;
      magnesium and cardiometabolic risk in patients innitiating an antipsychotic treatment. A&#xD;
      secondary objective is to specify the frequency, magnitude and time to onset of changes in&#xD;
      plasma of magnesium levels under antipsychotic treatment.&#xD;
&#xD;
      Methods : This is a pilot single-center prospective cohort. After inclusion, patients status&#xD;
      (including magnesium levels) will be evaluated (1 and 3 months of treatment) and that status&#xD;
      will define the exposure criterion. Included patients will be followed for 1 year during&#xD;
      which cardiometabolic markers will be measured.&#xD;
&#xD;
      Population : patients who are more than 18 years old with schizophrenia schizoaffective&#xD;
      disorder or bipolar disorder, naive to antipsychotic treatment or off for more than 3 months&#xD;
      and requiring the introduction of antipsychotic drug therapy. Patients will be recruited&#xD;
      during consultations and stays in care units of Adult Psychiatry Unit of Montpellier&#xD;
      University Hospital.&#xD;
&#xD;
      Factor studied: serum and intra-erythrocytic magnesium levels at beginning and during the&#xD;
      antipsychotic treatment measured by a unique analyzer center. Changes in levels of&#xD;
      hypomagnesemia expected during the treatment will determine exposure groups.&#xD;
&#xD;
      Outcome: cardiometabolic risk markers measured at the beginning and during the treatment will&#xD;
      be fasting blood glucose, fasting plasma insulin, HOMA-IR [Ins (uU / mL) x Gly (mmol / L) /&#xD;
      22.5], lipid profile (total cholesterol, LDL, HDL), BMI, waist circumference and ECG (QTc).&#xD;
&#xD;
      Cofactors: age, sex, personal and family medical history, blood pressure, smoking, diet,&#xD;
      physical activity, psychiatric disease, Global Impressions, anti-psychotic treatment and&#xD;
      comedications.&#xD;
&#xD;
      Perspectives : to show that decreased in magnesium levels observed among patients starting&#xD;
      antipsychotic treatment is associated with deterioration of cardiometabolic risk markers. The&#xD;
      demonstration of this association could explain at least part the increased cardiovascular&#xD;
      risk observed in this population. In the longer term, the results of this study would argue&#xD;
      the implementation of an intervention research project studying magnesium supplementation to&#xD;
      minimize the metabolic effects of antipsychotic medications.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a pilot single-center prospective cohort. After inclusion, patients status (including&#xD;
      magnesium levels) will be evaluated (1 and 3 months of treatment) and that status will define&#xD;
      the exposure criterion. Included patients will be followed for 1 year during which&#xD;
      cardiometabolic markers will be measured.&#xD;
&#xD;
      Patients will be recruited during consultations and stays in care units of Adult Psychiatry&#xD;
      Unit of Montpellier University Hospital.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">December 2017</completion_date>
  <primary_completion_date type="Anticipated">January 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients with changes from baseline cardiometabolic risk</measure>
    <time_frame>At 12 months</time_frame>
    <description>Changes from baseline cardiometabolic risk is defined the following composite outcome : 15% increase in fasting plasma glucose and/or 15% increase in plasma fasting insulin and/or 15% increase in HOMA-IR [Ins (uU / mL) x Gly (mmol / L) / 22.5] and/or 15% increase in total cholesterol levels, or LDL-cholesterol and/or reduction of 15% of HDL-cholesterol and/or 2 points increased in BMI and/or increase of 5 cm in waist circumference and/or 10 msec increase in the QTc interval of the ECG.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with changes from baseline cardiometabolic risk</measure>
    <time_frame>At 3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with changes from baseline cardiometabolic risk</measure>
    <time_frame>At 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with 15% increase in fasting plasma glucose</measure>
    <time_frame>From baseline at 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with 15% increase in plasma fasting insulin</measure>
    <time_frame>From baseline at 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with 15% increase in HOMA-IR [Ins (uU / mL) x Gly (mmol / L) / 22.5]</measure>
    <time_frame>From baseline at 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with 15% increase in total cholesterol levels, or LDL-cholesterol and/or reduction of 15% of HDL-cholesterol</measure>
    <time_frame>From baseline at 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with 2 points increased in BMI and/or increase of 5 cm in waist circumference</measure>
    <time_frame>From baseline at 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>9. Proportion of patients with 10 msec increase in the QTc interval of the ECG</measure>
    <time_frame>From baseline at 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in zincemia</measure>
    <time_frame>From baseline at 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in zincemia</measure>
    <time_frame>From baseline at 3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in zincemia</measure>
    <time_frame>From baseline at 6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Schizophrenia</condition>
  <condition>Schizoaffective Disorder</condition>
  <condition>Bipolar Disorder</condition>
  <arm_group>
    <arm_group_label>patient with antipsychotic/neuroleptic</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Blood sample performed on patients requiring the establishment of treatment with antipsychotic / neuroleptic</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Blood sample</intervention_name>
    <description>Blood sample</description>
    <arm_group_label>patient with antipsychotic/neuroleptic</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Patient with severe mental illness (schizophrenia and other disorders chronic&#xD;
             psychotic, schizoaffective disorder and bipolar disorder.&#xD;
&#xD;
          -  Patient naive to antipsychotic treatment or stopped for more than 3 months (more than&#xD;
             6 months for antipsychotic action extended) and requiring the introduction of&#xD;
             antipsychotic therapy&#xD;
&#xD;
          -  Patient informed and accepting the proposed follow-up (himself or his/her legal&#xD;
             representative)&#xD;
&#xD;
          -  Patient available for one year monitoring&#xD;
&#xD;
          -  Patient affiliated or beneficiary of a social security insurance&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  patient's opposition&#xD;
&#xD;
          -  Pregnant or breastfeeding patient&#xD;
&#xD;
          -  Patients on anti-psychotic or treatment stopped for less than 3 months (6 months for&#xD;
             antipsychotic prolonged action)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jean-Luc FAILLIE, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Montpellier University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jean-Luc FAILLIE, MD PhD</last_name>
    <phone>+33 4 67 33 67 52</phone>
    <email>jl-faillie@chu-montpellier.fr</email>
  </overall_contact>
  <location>
    <facility>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean-Luc FAILLIE, MD PhD</last_name>
      <phone>+33 4 67 33 67 52</phone>
      <email>jl-faillie@chu-montpellier.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2016</verification_date>
  <study_first_submitted>July 8, 2016</study_first_submitted>
  <study_first_submitted_qc>December 5, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 8, 2016</study_first_posted>
  <last_update_submitted>December 5, 2016</last_update_submitted>
  <last_update_submitted_qc>December 5, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 8, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mental disorders</keyword>
  <keyword>Antipsychotic agents</keyword>
  <keyword>Magnesium</keyword>
  <keyword>Cardiovascular risk factor</keyword>
  <keyword>Metabolic syndrome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
    <mesh_term>Bipolar Disorder</mesh_term>
    <mesh_term>Psychotic Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02986490
org study id: UF 9362
secondary id: 2014-A00381-46
nct id: NCT02986490
lead sponsor: 
has dmc: No
Background: Antipsychotics can induce metabolic disorders such as obesity, hyperglycemia,
      dyslipidemia or metabolic syndrome. It has been observed that treatment with antipsychotic
      could be accompanied by a decrease in the concentration of serum magnesium. Low serum
      concentrations of magnesium are potentially a risk factor of cardiac sudden death (Peacock,
      2010). Hypotheses linking magnesium and pathogenesis of cardiovacuscular diseases are
      multiple. Also, it seems to exist a close relationship between magnesium and carbohydrate
      metabolism. Most studies on the subject have generally studied plasmatic magnesium.

      Objective : Describe the relationship between changes in serum and intra-erythrocyte
      magnesium and cardiometabolic risk in patients innitiating an antipsychotic treatment. A
      secondary objective is to specify the frequency, magnitude and time to onset of changes in
      plasma of magnesium levels under antipsychotic treatment.

      Methods : This is a pilot single-center prospective cohort. After inclusion, patients status
      (including magnesium levels) will be evaluated (1 and 3 months of treatment) and that status
      will define the exposure criterion. Included patients will be followed for 1 year during
      which cardiometabolic markers will be measured.

      Population : patients who are more than 18 years old with schizophrenia schizoaffective
      disorder or bipolar disorder, naive to antipsychotic treatment or off for more than 3 months
      and requiring the introduction of antipsychotic drug therapy. Patients will be recruited
      during consultations and stays in care units of Adult Psychiatry Unit of Montpellier
      University Hospital.

      Factor studied: serum and intra-erythrocytic magnesium levels at beginning and during the
      antipsychotic treatment measured by a unique analyzer center. Changes in levels of
      hypomagnesemia expected during the treatment will determine exposure groups.

      Outcome: cardiometabolic risk markers measured at the beginning and during the treatment will
      be fasting blood glucose, fasting plasma insulin, HOMA-IR [Ins (uU / mL) x Gly (mmol / L) /
      22.5], lipid profile (total cholesterol, LDL, HDL), BMI, waist circumference and ECG (QTc).

      Cofactors: age, sex, personal and family medical history, blood pressure, smoking, diet,
      physical activity, psychiatric disease, Global Impressions, anti-psychotic treatment and
      comedications.

      Perspectives : to show that decreased in magnesium levels observed among patients starting
      antipsychotic treatment is associated with deterioration of cardiometabolic risk markers. The
      demonstration of this association could explain at least part the increased cardiovascular
      risk observed in this population. In the longer term, the results of this study would argue
      the implementation of an intervention research project studying magnesium supplementation to
      minimize the metabolic effects of antipsychotic medications.
This is a pilot single-center prospective cohort. After inclusion, patients status (including
      magnesium levels) will be evaluated (1 and 3 months of treatment) and that status will define
      the exposure criterion. Included patients will be followed for 1 year during which
      cardiometabolic markers will be measured.

      Patients will be recruited during consultations and stays in care units of Adult Psychiatry
      Unit of Montpellier University Hospital.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Proportion of patients with changes from baseline cardiometabolic risk
time frame: At 12 months
description: Changes from baseline cardiometabolic risk is defined the following composite outcome : 15% increase in fasting plasma glucose and/or 15% increase in plasma fasting insulin and/or 15% increase in HOMA-IR [Ins (uU / mL) x Gly (mmol / L) / 22.5] and/or 15% increase in total cholesterol levels, or LDL-cholesterol and/or reduction of 15% of HDL-cholesterol and/or 2 points increased in BMI and/or increase of 5 cm in waist circumference and/or 10 msec increase in the QTc interval of the ECG.
measure: Proportion of patients with changes from baseline cardiometabolic risk
time frame: At 3 months
measure: Proportion of patients with changes from baseline cardiometabolic risk
time frame: At 6 months
measure: Proportion of patients with 15% increase in fasting plasma glucose
time frame: From baseline at 12 months
measure: Proportion of patients with 15% increase in plasma fasting insulin
time frame: From baseline at 12 months
measure: Proportion of patients with 15% increase in HOMA-IR [Ins (uU / mL) x Gly (mmol / L) / 22.5]
time frame: From baseline at 12 months
measure: Proportion of patients with 15% increase in total cholesterol levels, or LDL-cholesterol and/or reduction of 15% of HDL-cholesterol
time frame: From baseline at 12 months
measure: Proportion of patients with 2 points increased in BMI and/or increase of 5 cm in waist circumference
time frame: From baseline at 12 months
measure: 9. Proportion of patients with 10 msec increase in the QTc interval of the ECG
time frame: From baseline at 12 months
measure: Change in zincemia
time frame: From baseline at 12 months
measure: Change in zincemia
time frame: From baseline at 3 months
measure: Change in zincemia
time frame: From baseline at 6 months
arm group label: patient with antipsychotic/neuroleptic
arm group type: Other
description: Blood sample performed on patients requiring the establishment of treatment with antipsychotic / neuroleptic
intervention type: Biological
intervention name: Blood sample
description: Blood sample
arm group label: patient with antipsychotic/neuroleptic
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean-Luc FAILLIE, MD PhD
role: Principal Investigator
affiliation: Montpellier University Hospital
last name: Jean-Luc FAILLIE, MD PhD
phone: +33 4 67 33 67 52
email: jl-faillie@chu-montpellier.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Schizophrenia
mesh term: Bipolar Disorder
mesh term: Psychotic Disorders
sharing ipd: No