Magnesium Variations and Cardiometabolic Risk in Patients With Antipsychotic Drugs

Influence of Magnesium Variations (Serum and Intra-erythrocyte) on Markers of Cardiometabolic Risk in Long-term Prescription of Antipsychotic Drugs: a Prospective Cohort Study

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.

Study Overview

• Status: Unknown
• Conditions: Schizophrenia; Schizoaffective Disorder; Bipolar Disorder
• Intervention / Treatment: Biological: Blood sample

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jean-Luc FAILLIE, MD PhD; Phone Number: +33 4 67 33 67 52; Email: jl-faillie@chu-montpellier.fr

Study Locations

• France
  • Montpellier, France, 34295
    • Recruiting
    • Contact: Jean-Luc FAILLIE, MD PhD; Phone Number: +33 4 67 33 67 52; Email: jl-faillie@chu-montpellier.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Patient with severe mental illness (schizophrenia and other disorders chronic psychotic, schizoaffective disorder and bipolar disorder.
• Patient naive to antipsychotic treatment or stopped for more than 3 months (more than 6 months for antipsychotic action extended) and requiring the introduction of antipsychotic therapy
• Patient informed and accepting the proposed follow-up (himself or his/her legal representative)
• Patient available for one year monitoring
• Patient affiliated or beneficiary of a social security insurance

Exclusion criteria:

• patient's opposition
• Pregnant or breastfeeding patient
• Patients on anti-psychotic or treatment stopped for less than 3 months (6 months for antipsychotic prolonged action)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: patient with antipsychotic/neuroleptic; Blood sample performed on patients requiring the establishment of treatment with antipsychotic / neuroleptic	Biological: Blood sample; Blood sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with changes from baseline cardiometabolic risk	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.	At 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with changes from baseline cardiometabolic risk	At 3 months
Proportion of patients with changes from baseline cardiometabolic risk	At 6 months
Proportion of patients with 15% increase in fasting plasma glucose	From baseline at 12 months
Proportion of patients with 15% increase in plasma fasting insulin	From baseline at 12 months
Proportion of patients with 15% increase in HOMA-IR [Ins (uU / mL) x Gly (mmol / L) / 22.5]	From baseline at 12 months
Proportion of patients with 15% increase in total cholesterol levels, or LDL-cholesterol and/or reduction of 15% of HDL-cholesterol	From baseline at 12 months
Proportion of patients with 2 points increased in BMI and/or increase of 5 cm in waist circumference	From baseline at 12 months
9. Proportion of patients with 10 msec increase in the QTc interval of the ECG	From baseline at 12 months
Change in zincemia	From baseline at 12 months
Change in zincemia	From baseline at 3 months
Change in zincemia	From baseline at 6 months

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Jean-Luc FAILLIE, MD PhD, Montpellier University Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Anticipated): January 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: July 8, 2016
• First Submitted That Met QC Criteria: December 5, 2016
• First Posted (Estimate): December 8, 2016

Study Record Updates

• Last Update Posted (Estimate): December 8, 2016
• Last Update Submitted That Met QC Criteria: December 5, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Metabolic syndrome; Mental disorders; Magnesium; Antipsychotic agents; Cardiovascular risk factor
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Schizophrenia Spectrum and Other Psychotic Disorders; Bipolar and Related Disorders; Schizophrenia; Disease; Psychotic Disorders; Bipolar Disorder
• Other Study ID Numbers: UF 9362; 2014-A00381-46 (Other Identifier: FRANCE: Agence Nationale de Sécurité des Médicaments)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO