Comparison of Aripiprazole Versus Higher Metabolic Risk Antipsychotic Drugs on Adiposity Using MRI

Completed

• Conditions: Psychotic Disorders; Metabolic Syndrome X; Bipolar Disorder
• Interventions: Drug: Risperidone/Quetiapine; Drug: Aripiprazole

• Registration Number: NCT01739127
• Lead Sponsor: University of British Columbia

Brief Summary

The purpose of this study is to compare abdominal weight gain and fat distribution in people taking aripiprazole versus risperidone or quetiapine, to people not taking any of these antipsychotic medications.

Detailed Description

Second generation antipsychotic drugs have much greater efficacy for refractory schizophrenia and have much lower propensity to induce motor side-effects. These medications are seeing increased use for indications other than psychosis, and greater use in populations such as adolescents. However, one of the most critical issues in the field of psychiatry today is the overwhelming evidence that chronic use of the second generation antipsychotics can result in metabolic dysregulation, which includes weight gain, hyperlipidemia, and insulin resistance. A recent meta-analysis indicated that switching from other second generation antipsychotics to the antipsychotic drug aripiprazole consistently resulted in significant weight loss and may be an optimal treatment for patients who exhibit drug-induced weight gain. Therefore, we aim to compare metabolic dysregulation (namely abdominal weight gain and fat distribution)in participants taking aripiprazole, to participants who are taking higher-metabolic propensity antipsychotic drugs (such as risperidone or quetiapine), and to healthy participants.

Study Timeline

• Study Start: 2012-11
• Study First Submitted: 2012-11-27
• Study First Submitted QC: 2012-11-29
• Study First Posted: 2012-12-03
• Primary Completion: 2016-02
• Study Completion: 2016-02
• Status Verified: 2016-05
• Last Update Submitted: 2016-05-24
• Last Update Posted: 2016-05-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 83

Inclusion Criteria

• Male or female, aged 12+ years for healthy participants or participants with bipolar disorder; or aged 15+ years for participants with non-affective psychosis.
• Recent admission to hospital for psychiatric services related to first-episode psychosis or first-episode bipolar disorder.
• Participants being treated with an antipsychotic medication principally for psychosis or for bipolar disorder.
• Participants taking aripiprazole must be taking a dose of at least 10mg/day for the duration of the study.
• Participants must have received no more than 12 weeks of total lifetime exposure to antipsychotics.
• Participants may be in- or outpatients.
• Participants able to give informed consent, or informed consent through legally authorized representative.

Exclusion Criteria

• Previous total lifetime exposure to antipsychotics of more than 12 weeks.
• Previously diagnosed with diabetes mellitus, seizure disorders, mental retardation (IQ < 70), or pregnancy (current or within 3 months postpartum).
• Participants who have been treated/are currently being treated with mood stabilizers (paroxetine, lithium, or valproic acid). Prior or concurrent use of Selective Serotonin Reuptake Inhibitor antidepressants (other than paroxetine) is acceptable.
• Received chemotherapy for cancer treatment in the 4 weeks prior to baseline or 16-week follow-up visit.
• Participants who are not able to fluently communicate in English.
• Contraindicated for MRI scan (i.e., has had major surgery in the last 6 months, morbid obesity, claustrophobia, and/or has metal in their bodies from a surgical intervention or working in metalwork, or is unsure if metal is present in their bodies, etc.).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Risperidone/Quetiapine	Risperidone/Quetiapine	Participants receiving treatment with either risperidone or quetiapine, as prescribed to them by their psychiatrists.
Aripiprazole	Aripiprazole	Participants receiving treatment with at least 10mg aripiprazole per day, as prescribed to them by their psychiatrists.

Primary Outcome Measures

Name	Time	Method
Abdominal distribution of visceral fat versus subcutaneous fat	Baseline (within 12 weeks of starting antipsychotic treatment), and 16 weeks later	Change over time, and between groups, in amounts of visceral and subcutaneous fat as measured by automated segmentation of a magnetic resonance image (MRI).

Secondary Outcome Measures

Name	Time	Method
Metabolic measures	Baseline (within 12 weeks of starting an antipsychotic), and 16 weeks later	Comparing change in the levels of hemoglobin, fasting lipid levels, adiponectin, leptin, insulin, and glucagon-like peptide 1 (GLP-1).
Potential genetic factors of antipsychotic-induced weight gain	Sample to be taken after 16 weeks of participation in the study	DNA will be extracted and amplified using polymerase chain reaction (PCR), and the presence or absence of certain single nucleotide polymorphisms will be identified by using primers.
Fat content of the liver	Baseline (within 12 weeks of starting an antipsychotic), and 16 weeks later	Change over time, and between groups, in the amount of fat accumulation in the liver as measured by magnetic resonance spectroscopy (MRS).
Glucose intolerance	Baseline (within 12 weeks of starting an antipsychotic), and 16 weeks later	Change over time, and between groups, in ability to tolerate a glucose challenge as measured by an oral glucose tolerance test (OGTT).

Trial Locations

Locations (1)

BC Mental Health & Addictions Research Institute; 🇨🇦 Vancouver, British Columbia, Canada