Magnesium Variations and Cardiometabolic Risk in Patients With Antipsychotic Drugs

Sponsor

University Hospital, Montpellier (Other)

Overall Status

Unknown status

CT.gov ID

NCT02986490

Collaborator

(none)

100

Enrollment

Location

Arm

Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Schizoaffective Disorder Bipolar Disorder	Biological: Blood sample	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

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

Study Start Date :

Sep 1, 2014

Anticipated Primary Completion Date :

Jan 1, 2017

Anticipated Study Completion Date :

Dec 1, 2017

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Proportion of patients with changes from baseline cardiometabolic risk [At 12 months]
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.

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)