Magnesium Variations and Cardiometabolic Risk in Patients With Antipsychotic Drugs

Schizophrenia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02986490
• Other study ID #: UF 9362
• Secondary ID: 2014-A00381-46
• Status: Recruiting
• Phase: N/A
• First received: July 8, 2016
• Last updated: December 5, 2016
• Start date: September 2014
• Est. completion date: December 2017

Study information

• Verified date: July 2016
• Source: University Hospital, Montpellier
• Contact: Jean-Luc FAILLIE, MD PhD
• Phone: +33 4 67 33 67 52
• Email: jl-faillie[@]chu-montpellier.fr
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bipolar Disorder
• Disease
• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia

Intervention

Biological:
• Blood sample
Blood sample

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Montpellier

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Proportion of patients with changes from baseline cardiometabolic risk		At 3 months	No
Secondary	Proportion of patients with changes from baseline cardiometabolic risk		At 6 months	No
Secondary	Proportion of patients with 15% increase in fasting plasma glucose		From baseline at 12 months	No
Secondary	Proportion of patients with 15% increase in plasma fasting insulin		From baseline at 12 months	No
Secondary	Proportion of patients with 15% increase in HOMA-IR [Ins (uU / mL) x Gly (mmol / L) / 22.5]		From baseline at 12 months	No
Secondary	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	No
Secondary	Proportion of patients with 2 points increased in BMI and/or increase of 5 cm in waist circumference		From baseline at 12 months	No
Secondary	9. Proportion of patients with 10 msec increase in the QTc interval of the ECG		From baseline at 12 months	No
Secondary	Change in zincemia		From baseline at 12 months	No
Secondary	Change in zincemia		From baseline at 3 months	No
Secondary	Change in zincemia		From baseline at 6 months	No