SchizophreniaGlulipidNCT00515723
Glucose and Lipid Metabolism on Antipsychotic Medication
A study testing risperidone, olanzapine and quetiapine in people with Schizophrenia and Schizoaffective Disorder, run by Washington University School of Medicine at 2 sites in United States.
Trial summary
This project aims to a) evaluate the effects of selected antipsychotic medications on insulin action in skeletal muscle (glucose disposal), liver (glucose production) and adipose tissue (whole-body lipolysis), b) evaluate the effects of selected antipsychotic medications on abdominal adipose tissue mass, total body… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder, Type 2 Diabetes Mellitus
- What is being tested?
- risperidone, olanzapine and quetiapine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2001to Dec 2008
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Aged 18-60 years
- Patients: otherwise healthy and meets DSM-IV criteria for schizophrenia or schizoaffective disorder, any type, treated with haloperidol, olanzapine, clozapine, quetiapine, ziprasidone, aripiprazole, or risperidone for at least 3 months
- Controls: healthy
- Able to give informed consent
- No antipsychotic medication changes for 3 months, and no other medication changes for 2 weeks prior to Baseline Evaluations.
Who cannot join
- Axis I psychiatric disorder criteria met in self except for substance use disorders as below
- Patients and controls: meets DSM-IV criteria for the diagnoses of substance abuse within the past 3 months
- Involuntary legal status (as per Missouri law)
- The presence of any serious medical disorder that may confound the assessment of relevant biologic measures or diagnosis, including: significant organ system dysfunction, metabolic diseases, type 1 diabetes mellitus, symptomatic type 2 diabetes mellitus (see below), pregnancy, endocrine disease, coagulopathy, clinically significant anemia, that would preclude blood sampling (as determined by the PI) or acute infection;
- Patients taking more than one atypical antipsychotic medication;
- Subjects taking certain prescription medications (as determined by PI on a case by case basis).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Washington Univeristy School of Medicine
St Louis, Missouri, 63110
Washington University School of Medicine, Psychiatry Dept.
St Louis, Missouri, 63110
About this study
This project aims to a) evaluate the effects of selected antipsychotic medications on insulin action in skeletal muscle (glucose disposal), liver (glucose production) and adipose tissue (whole-body lipolysis), b) evaluate the effects of selected antipsychotic medications on abdominal adipose tissue mass, total body fat and total fat-free mass, and c) explore the longitudinal effects of treatment with selected antipsychotics on glucose tolerance, lipid profiles, abdominal adipose tissue mass, total body fat and total fat-free mass. These hypotheses will be evaluated by measuring 1) whole-body glucose and lipid kinetics with the use of "gold-standard" stable isotope tracer methodology, 2) body composition using dual energy x-ray absorptiometry and magnetic resonance imaging, and 3) longitudinal changes in glucose tolerance and lipid profiles. The aims will be addressed in non-diabetic schizophrenia patients chronically treated with risperidone, olanzapine, clozapine, quetiapine, ziprasidone, or haloperidol, and untreated healthy controls. Re-evaluations will also be performed in patients who are randomized to switch from their current antipsychotic (from the above groups) to risperidone, olanzapine, quetiapine, or ziprasidone for 6 months. Relevant data is critically needed to target basic research, identify long-term cardiovascular consequences, and plan therapeutic interventions.
Read the detailed description
Hyperglycemia and type 2 diabetes mellitus are more common in schizophrenia than in the general population. Type 2 diabetes mellitus is characterized by disturbances in insulin action on skeletal muscle, liver and adipose tissue. Diabetes causes increased morbidity and mortality due to acute (e.g., diabetic ketoacidosis) and long-term (e.g., cardiovascular disease) complications. The combination of hyperglycemia, dyslipidemia and abdominal adiposity is even more strongly associated with increased cardiovascular morbidity and mortality. The association of type 2 diabetes and hyperglycemia with schizophrenia was first noted prior to the introduction of antipsychotic medications, suggesting that these patients may be at increased risk. Since then, however, additional glucoregulatory abnormalities (e.g., new onset diabetes), dyslipidemia, and increased weight and adiposity have all been associated with antipsychotic medications. Concern about antipsychotic effects on glucose, lipids and adiposity has increased recently, focusing on the widely-used newer medications, clozapine and olanzapine. Increased abdominal adiposity can secondarily decrease insulin sensitivity and antipsychotics can increase adiposity. However, medication effects on glucose control and insulin action may also occur independent of differences in adiposity. This project aims to a) evaluate the effects of selected antipsychotic medications on insulin action in skeletal muscle (glucose disposal), liver (glucose production) and adipose tissue (whole-body lipolysis), b) evaluate the effects of selected antipsychotic medications on abdominal adipose tissue mass, total body fat and total fat-free mass, and c) explore the longitudinal effects of treatment with selected antipsychotics on glucose tolerance, lipid profiles, abdominal adipose tissue mass, total body fat and total fat-free mass. These hypotheses will be evaluated by measuring 1) whole-body glucose and lipid kinetics with the use of "gold-standard" stable isotope tracer methodology, 2) body composition using dual energy x-ray absorptiometry and magnetic resonance imaging, and 3) longitudinal changes in glucose tolerance and lipid profiles. The aims will be addressed in non-diabetic schizophrenia patients chronically treated with risperidone, olanzapine, clozapine, quetiapine, ziprasidone, or haloperidol, and untreated healthy controls. Re-evaluations will also be performed in patients who are randomized to switch from their current antipsychotic (from the above groups) to risperidone, olanzapine, quetiapine, or ziprasidone for 6 months. Relevant data is critically needed to target basic research, identify long-term cardiovascular consequences, and plan therapeutic interventions.
- Being tested
- risperidone, olanzapine, quetiapine, ziprasidone
- Keywords
- control, risperidone, olanzapine, quetiapine, ziprasidone
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Diabetes Mellitus, Type 2, Hyperglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
risperidoneDrug
Also called Risperdal
randomized to 12 week trial of risperidone.
olanzapineDrug
Also called Zyprexa
randomized to 12 week trial of olanzapine.
quetiapineDrug
Also called Seroquel
randomized to 12 week trial of quetiapine.
ziprasidoneDrug
Also called Geodon
randomized to 12 week trial of ziprasidone.
| Study group | Role | What they receive |
|---|---|---|
| Olanzapine | Active comparator | Participants in this group were randomized to flexibly-dosed treatment with olanzapine. Receives: Drug: olanzapine |
| Risperidone | Active comparator | Participants in this group were randomized to flexibly-dosed treatment with risperidone. Receives: Drug: risperidone |
| Quetiapine | Active comparator | Participants in this group were randomized to flexibly-dosed treatment with quetiapine. Receives: Drug: quetiapine |
| Ziprasidone | Active comparator | Participants in this group were randomized to flexibly-dosed treatment with ziprasidone. Receives: Drug: ziprasidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
DEXA Total Fat
This study hypothesized that antipsychotic treatment would increase total body fat, as measured by whole body dual energy x-ray absorptiometry (DEXA), with larger adverse effects for olanzapine.
Measured: The relevant time points include baseline, week 6 and week 12.
Clamp Derived Insulin Sensitivity (mg/kg/Min)
This study hypothesized that antipsychotic treatment would decrease insulin sensitivity, with larger adverse effects for olanzapine. Insulin sensitivity describes how sensitive the body is to the effects of insulin.
Measured: The relevant time points include baseline and week 12.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2007 (estimated)
- Study startSep 2001
- Primary completionDec 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- John W Newcomer, MD, Principal investigator, Washington Univerisity School of Medicine and Florida Atlantic University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00515723
- Sponsor's protocol ID
- R01MH063985-04
- Other IDs
- R01MH063985-04
- Acronym
- Glulipid
- Status last verified
- Oct 2019
- First submitted
- 13 Aug 2007
- Last updated
- 2 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glucose and Lipid Metabolism on Antipsychotic Medication
- ClinicalTrials.gov ID
- NCT00515723
- Acronym / sponsor ID
- Glulipid / R01MH063985-04
- Keywords
- control, risperidone, olanzapine, quetiapine, ziprasidone
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Sep 2001
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 14 Aug 2007 (estimated)
- Results
- Posted 2 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This project aims to a) evaluate the effects of selected antipsychotic medications on insulin action in skeletal muscle (glucose disposal), liver (glucose production) and adipose tissue (whole-body lipolysis), b) evaluate the effects of selected antipsychotic medications on abdominal adipose tissue mass, total body fat and total fat-free mass, and c) explore the longitudinal effects of treatment with selected antipsychotics on glucose tolerance, lipid profiles, abdominal adipose tissue mass, total body fat and total fat-free mass. These hypotheses will be evaluated by measuring 1) whole-body glucose and lipid kinetics with the use of "gold-standard" stable isotope tracer methodology, 2) body composition using dual energy x-ray absorptiometry and magnetic resonance imaging, and 3) longitudinal changes in glucose tolerance and lipid profiles. The aims will be addressed in non-diabetic schizophrenia patients chronically treated with risperidone, olanzapine, clozapine, quetiapine, ziprasidone, or haloperidol, and untreated healthy controls. Re-evaluations will also be performed in patients who are randomized to switch from their current antipsychotic (from the above groups) to risperidone, olanzapine, quetiapine, or ziprasidone for 6 months. Relevant data is critically needed to target basic research, identify long-term cardiovascular consequences, and plan therapeutic interventions.
Detailed description
Hyperglycemia and type 2 diabetes mellitus are more common in schizophrenia than in the general population. Type 2 diabetes mellitus is characterized by disturbances in insulin action on skeletal muscle, liver and adipose tissue. Diabetes causes increased morbidity and mortality due to acute (e.g., diabetic ketoacidosis) and long-term (e.g., cardiovascular disease) complications. The combination of hyperglycemia, dyslipidemia and abdominal adiposity is even more strongly associated with increased cardiovascular morbidity and mortality. The association of type 2 diabetes and hyperglycemia with schizophrenia was first noted prior to the introduction of antipsychotic medications, suggesting that these patients may be at increased risk. Since then, however, additional glucoregulatory abnormalities (e.g., new onset diabetes), dyslipidemia, and increased weight and adiposity have all been associated with antipsychotic medications. Concern about antipsychotic effects on glucose, lipids and adiposity has increased recently, focusing on the widely-used newer medications, clozapine and olanzapine. Increased abdominal adiposity can secondarily decrease insulin sensitivity and antipsychotics can increase adiposity. However, medication effects on glucose control and insulin action may also occur independent of differences in adiposity. This project aims to a) evaluate the effects of selected antipsychotic medications on insulin action in skeletal muscle (glucose disposal), liver (glucose production) and adipose tissue (whole-body lipolysis), b) evaluate the effects of selected antipsychotic medications on abdominal adipose tissue mass, total body fat and total fat-free mass, and c) explore the longitudinal effects of treatment with selected antipsychotics on glucose tolerance, lipid profiles, abdominal adipose tissue mass, total body fat and total fat-free mass. These hypotheses will be evaluated by measuring 1) whole-body glucose and lipid kinetics with the use of "gold-standard" stable isotope tracer methodology, 2) body composition using dual energy x-ray absorptiometry and magnetic resonance imaging, and 3) longitudinal changes in glucose tolerance and lipid profiles. The aims will be addressed in non-diabetic schizophrenia patients chronically treated with risperidone, olanzapine, clozapine, quetiapine, ziprasidone, or haloperidol, and untreated healthy controls. Re-evaluations will also be performed in patients who are randomized to switch from their current antipsychotic (from the above groups) to risperidone, olanzapine, quetiapine, or ziprasidone for 6 months. Relevant data is critically needed to target basic research, identify long-term cardiovascular consequences, and plan therapeutic interventions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Olanzapine | Active comparator | Drug: olanzapineParticipants in this group were randomized to flexibly-dosed treatment with olanzapine. |
| Risperidone | Active comparator | Drug: risperidoneParticipants in this group were randomized to flexibly-dosed treatment with risperidone. |
| Quetiapine | Active comparator | Drug: quetiapineParticipants in this group were randomized to flexibly-dosed treatment with quetiapine. |
| Ziprasidone | Active comparator | Drug: ziprasidoneParticipants in this group were randomized to flexibly-dosed treatment with ziprasidone. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Aged 18-60 years
- Patients: otherwise healthy and meets DSM-IV criteria for schizophrenia or schizoaffective disorder, any type, treated with haloperidol, olanzapine, clozapine, quetiapine, ziprasidone, aripiprazole, or risperidone for at least 3 months
- Controls: healthy
- Able to give informed consent
- No antipsychotic medication changes for 3 months, and no other medication changes for 2 weeks prior to Baseline Evaluations.
Key exclusion criteria (6 listed)
- Axis I psychiatric disorder criteria met in self except for substance use disorders as below
- Patients and controls: meets DSM-IV criteria for the diagnoses of substance abuse within the past 3 months
- Involuntary legal status (as per Missouri law)
- The presence of any serious medical disorder that may confound the assessment of relevant biologic measures or diagnosis, including: significant organ system dysfunction, metabolic diseases, type 1 diabetes mellitus, symptomatic type 2 diabetes mellitus (see below), pregnancy, endocrine disease, coagulopathy, clinically significant anemia, that would preclude blood sampling (as determined by the PI) or acute infection;
- Patients taking more than one atypical antipsychotic medication;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| risperidoneAlso: Risperdalrandomized to 12 week trial of risperidone. | Drug | Risperidone |
| olanzapineAlso: Zyprexarandomized to 12 week trial of olanzapine. | Drug | Olanzapine |
| quetiapineAlso: Seroquelrandomized to 12 week trial of quetiapine. | Drug | Quetiapine |
| ziprasidoneAlso: Geodonrandomized to 12 week trial of ziprasidone. | Drug | Ziprasidone |
Primary outcome
DEXA Total Fat
Time frame: The relevant time points include baseline, week 6 and week 12.
This study hypothesized that antipsychotic treatment would increase total body fat, as measured by whole body dual energy x-ray absorptiometry (DEXA), with larger adverse effects for olanzapine.
Clamp Derived Insulin Sensitivity (mg/kg/Min)
Time frame: The relevant time points include baseline and week 12.
This study hypothesized that antipsychotic treatment would decrease insulin sensitivity, with larger adverse effects for olanzapine. Insulin sensitivity describes how sensitive the body is to the effects of insulin.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Schizophrenia
RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
Not yet recruiting
Deep Brain Stimulation for Treatment-Resistant Schizophrenia
Treatment Resistant Disorders
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Designing and Evaluating a Classroom-Based Mental Health Programme for Adolescents.
Mental Health Promotion
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John W Newcomer, MD principal investigator
Washington Univerisity School of Medicine and Florida Atlantic University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing risperidone, olanzapine and quetiapine in people with Schizophrenia and Schizoaffective Disorder, run by Washington University School of Medicine at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DEXA Total Fat (time frame: The relevant time points include baseline, week 6 and week 12.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2019.