Body Mass Index (BMI) and Metabolic Changes Following Switch to Aripiprazole From Olanzapine, Risperidone and Quetiapine

NCT ID: NCT00312598

Last Updated: 2014-01-13

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2010-04-30

Brief Summary

Weight gain is a serious, common side effect of many antipsychotic medications. On average, the highest amounts of weight gain are found to occur in people taking clozaril and olanzapine, but with significant weight gain occuring in those on the other atypical antipsychotics as well.

We, the researchers at the University of North Carolina, propose an open-label observational, pilot study of the changes in weight, BMI, body composition, and lipids, glucose, insulin and other metabolic parameters occurring in subjects as they switch from treatment with olanzapine, risperidone or quetiapine to aripiprazole. This medication switch will be determined prior to their entering this study by their treating psychiatrist. We also will determine resting energy expenditure (REE) and respiratory quotient (RQ) as measured by metabolic cart to determine if either energy expenditure or the propensity to store energy as fat may be involved in any changes to weight that are detected. Food intake, hunger, and physical activity will also be assessed.

Detailed Description

Weight gain is a serious, common side effect of many antipsychotic medications. It is a frequent cause of poor adherence to antipsychotic medications and a major contributor to medical problems including Syndrome X, various cancers, osteoarthritis and sleep apnea. Syndrome X, also called the Metabolic Syndrome, is a constellation of abnormalities of metabolism that confer a high risk of coronary heart disease. Syndrome X includes glucose intolerance, dyslipidemia, hypertension, and central obesity. Long-term patients on antipsychotic medications have markedly increased rates of Syndrome X that are consistent with increased cardiovascular morbidity and decreased life expectancy.

A recent meta-analysis estimated weight gain at 10 weeks of treatment for a variety of antipsychotics and found that clozapine had the highest average weight gain (4.45 kg), followed by olanzapine (4.15 kg), quetiapine (2.2 kg), risperidone (2.18 kg), and ziprasidone (0.04 kg) . For some drugs weight gain continues over many months, with the time to plateau being directly related to the initial degree of weight gain. Early data for the most recently approved antipsychotic, aripiprazole, shows it to be weight neutral but the characteristics of its effects on weight are still to be determined. A recent publication of 224 subjects switching by three different switching strategies from haloperidol, thioridazine, risperidone or olanzapine to aripiprazole found weight loss of between 1.3 and 1.7 kg after 8 weeks on aripiprazole. Cholesterol levels improved in subjects switching from olanzapine to aripiprazole.

Atypical antipsychotic medications that can improve the factors associated with Syndrome X could offer a very attractive alternative for patients who have already developed this constellation of symptoms during treatment with other antipsychotics. It is not known if a switch to aripiprazole from an atypical antipsychotic medication that has caused excessive weight gain and/or abnormalities of glucose, lipids or blood pressure will result in significant improvement in these factors or simply halt worsening. If worsening is only halted, then switch from a weight-inducing drug to aripiprazole should be done early. If factors associated with Syndrome X can be reversed, then switch to aripiprazole would be very beneficial even after abnormalities have developed.

We propose an open-label pilot study of the changes in weight, BMI, body composition, and lipids, glucose, insulin and other metabolic parameters occurring in subjects as they switch from treatment with olanzapine, risperidone or quetiapine to aripiprazole. We also will determine resting energy expenditure (REE) and respiratory quotient (RQ) as measured by metabolic cart to determine if either energy expenditure or the propensity to store energy as fat may be involved in any changes to weight that are detected. Food intake, hunger, and physical activity will also be assessed.

Recruited subjects will enter a screening phase where patient eligibility is determined through assessments of psychiatric and physical health, including physical examination, blood tests and urine drug screen. Subjects not meeting eligibility criteria will be discontinued.

Thirty subjects will be enrolled into this open label study. At entry into the study, anthropometric measures (wt, ht, waist, hip), body composition, respiratory quotient (RQ), resting energy expenditure (REE), and measures of food intake, hunger, and physical activity will be assessed. Additionally, the Positive and Negative Symptom Scale (PANSS) will be used to assess clinical status and all women will have a blood pregnancy test as required prior to having a DXA scan. Following completion of these assessments, subjects will begin a two week cross-taper from their current antipsychotic to aripiprazole. Psychiatric symptoms, weight, medical status and medication query will be reassessed after 2, 4, 8 and 12 weeks. RQ and hunger will be reassessed at the 4 week time point. Fasting bloodwork, pregnancy test, urine drug screen, vital signs, and all baseline assessments will be repeated at the 12 week time point or at early termination. During the study, dosage of aripiprazole will be tailored to each subject's need based on symptoms and side effects, and will remain at or below the maximum recommended dosage.

Conditions

Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder; Mood Disorders

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

aripiprazole

observational measures of metabolic parameters of subjects who are making clinically determined medication switch to aripiprazole

Aripiprazole

Intervention Type: DRUG

Interventions

Aripiprazole

Intervention Type: DRUG

Other Intervention Names

Abilify

Eligibility Criteria

Inclusion Criteria

• Any ethnicity
• Antipsychotic monotherapy with olanzapine, risperidone or quetiapine for minimum of 1 month at entry into study and with weight gain of 2 BMI units while on this medication or development of abnormalities of glucose (greater than 110 mg/dl fasting), lipids (total cholesterol [TC], high-density lipoprotein [HDL], triglycerides [TG], or low-density lipoprotein [LDL] greater than 10% change) or blood pressure (greater than 20 mmHg change in systolic or diastolic)
• Antipsychotic monotherapy with aripiprazole is planned by the subject's treating psychiatrist.
• Subjects able to fully participate in the informed consent process
• Female subjects of childbearing potential must be using a medically accepted means of contraception which includes tubal ligation, hysterectomy, condoms, oral contraceptives, intrauterine device (IUD), cervical cap, diaphragm, transdermal contraceptive patch, and abstinence.

Exclusion Criteria

• Subjects have had a previous trial of aripiprazole
• Serious or unstable medical illness which requires ongoing treatment with medication. This does not include non-insulin dependent diabetes, dyslipidemia or hypertension.
• At serious suicidal risk.
• Subjects with substance abuse or dependence.
• Female subjects who are either pregnant or nursing.
• Known history of mental retardation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Karen Graham, MD

associate professor of psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Karen A Graham, MSc MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Other Identifiers

GCRC 2086

Identifier Type: -

Identifier Source: secondary_id

IND 70,111

Identifier Type: -

Identifier Source: org_study_id