Insulin ResistanceDepIVGTTNCT00552500
Effects of Atypical Antipsychotic and Valproate Combination Therapy on Glucose and Lipid Metabolism in Schizophrenia
A study testing Depakote (valproate) in people with Insulin Resistance and Body Composition, run by Washington University School of Medicine at 1 site in United States.
Trial summary
This project aims to a) evaluate the effects of haloperidol, olanzapine, and risperidone in combination with valproate on insulin secretion and insulin actions, b) evaluate medication effects on abdominal fat, total body fat and total fat-free mass, and c) evaluate treatment effects on glucose tolerance, lipid… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Insulin Resistance, Body Composition
- What is being tested?
- Depakote (valproate)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2003to Dec 2005
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Meets DSM-IV criteria for schizophrenia, any type, treated with atypical or high potency typical neuroleptics for at least 3 months
- Aged 18 to 60 years
- 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
- Meets DSM-IV criteria for the diagnoses of substance abuse or dependence within the past 6 months
- Involuntary legal status (as per Missouri law)
- The presence of any serious medical disorder that may (as confirmed by peer-reviewed literature) confound the assessment of symptoms, relevant biologic measures or diagnosis. The following conditions are currently identified:
- Type 1 diabetes mellitus or symptomatic type 2 diabetes mellitus
- Any intra-abdominal or intrathoracic surgery or limb amputation within the prior 6 months
- Any diagnosed cardiac condition causing documented hemodynamic compromise
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- Any diagnosed respiratory condition causing documented or clinically recognized hypoxia
- Pregnancy or high dose estrogens, fever, narcotic therapy, acute sedative hypnotic withdrawal, corticosteroid or spironolactone therapy, dehydration, epilepsy, endocrine disease, high-dose benzodiazepine therapy (> 25 mg/day of diazepam), or any medical condition known to interfere with glucose utilization
- Meets DSM-IV criteria for Mental Retardation (mild or worse).
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
This project aims to a) evaluate the effects of haloperidol, olanzapine, and risperidone in combination with valproate on insulin secretion and insulin actions, b) evaluate medication effects on abdominal fat, total body fat and total fat-free mass, and c) evaluate treatment effects on glucose tolerance, lipid profiles, and plasma levels of leptin, adiponectin, ghrelin and C-reactive protein. Hypotheses will be evaluated by measuring 1) insulin action and secretion using frequently sampled intravenous glucose tolerance tests, 2) body composition using dual energy x-ray absorptiometry, magnetic resonance scans, and anthropomorphic measurements, and 3) changes in hormone levels and lipid profiles. The aims will be addressed in non-diabetic schizophrenia patients chronically treated with haloperidol, olanzapine or risperidone who will have valproate added to their treatment. Relevant data is critically needed to target basic research, identify long-term cardiovascular risks, and plan therapeutic interventions.
Read the detailed description
Schizophrenia is associated with increased rates of obesity, hyperglycemia, dyslipidemia and type 2 diabetes mellitus, causing increased morbidity and mortality due to acute (e.g., diabetic ketoacidosis) and long-term (e.g., vascular disease) complications. The association of type 2 diabetes and hyperglycemia with schizophrenia was first noted prior to the introduction of antipsychotic medications. However, additional glucoregulatory abnormalities, dyslipidemia, and increased adiposity have all been associated with antipsychotics. Risperidone and olanzapine are the most prescribed antipsychotics for schizophrenia in the U.S. In addition, schizophrenia patients in clinical practice are commonly treated with multi-class polypharmacy, with 35% of atypical antipsychotic prescriptions accompanied by co-prescription of valproate. This combination continues to increase in popularity, despite reports that the addition of valproate may further disturb glucose and lipid metabolism and weight regulation. While sensitive and validated measures of glucose and lipid metabolism and weight regulation are available, very few studies have addressed the metabolic consequences of this common type of polypharmacy.
This project aims to a) evaluate the effects of haloperidol, olanzapine, and risperidone in combination with valproate on insulin secretion and insulin actions, b) evaluate medication effects on abdominal fat, total body fat and total fat-free mass, and c) evaluate treatment effects on glucose tolerance, lipid profiles, and plasma levels of leptin, adiponectin, ghrelin and C-reactive protein. Hypotheses will be evaluated by measuring 1) insulin action and secretion using frequently sampled intravenous glucose tolerance tests, 2) body composition using dual energy x-ray absorptiometry, magnetic resonance scans, and anthropomorphic measurements, and 3) changes in hormone levels and lipid profiles. The aims will be addressed in non-diabetic schizophrenia patients chronically treated with haloperidol, olanzapine or risperidone who will have valproate added to their treatment. Relevant data is critically needed to target basic research, identify long-term cardiovascular risks, and plan therapeutic interventions.
- Conditions
- Insulin Resistance, Body Composition
- Being tested
- Depakote (valproate)
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Depakote (valproate)Drug
500 mg -2000 mg QD based on individual tolerance and VPA levels
| Study group | Role | What they receive |
|---|---|---|
| Schizophrenics | Active comparator | i) meets DSM-IV criteria for schizophrenia, any type, treated with atypical or high potency typical neuroleptics for at least 3 months; ii) aged 18 to 60 years; iii) able to give informed consent; iv) no antipsychotic medication changes for 3 months, and no other medication changes for 2 weeks prior to Baseline Evaluations. Receives: Drug: Depakote (valproate) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hypotheses will be evaluated by measuring insulin action and secretion using frequently sampled intravenous glucose tolerance tests
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2007 (estimated)
- Study startFeb 2003
- Primary completionDec 2005
- Study completionDec 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin ResistanceStudies 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
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Daniel W Haupt, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00552500
- Sponsor's protocol ID
- NARSAD 43625
- Other IDs
- NARSAD
- Acronym
- DepIVGTT
- Status last verified
- Jun 2018
- First submitted
- 1 Nov 2007
- Last updated
- 21 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Atypical Antipsychotic and Valproate Combination Therapy on Glucose and Lipid Metabolism in Schizophrenia
- ClinicalTrials.gov ID
- NCT00552500
- Acronym / sponsor ID
- DepIVGTT / NARSAD 43625
- Conditions
- Insulin Resistance, Body Composition
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Feb 2003 (actual)
- Primary completion
- Dec 2005 (actual)
- Study completion
- Dec 2005 (actual)
- First posted
- 2 Nov 2007 (estimated)
- Results
- Not posted in the source record
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 haloperidol, olanzapine, and risperidone in combination with valproate on insulin secretion and insulin actions, b) evaluate medication effects on abdominal fat, total body fat and total fat-free mass, and c) evaluate treatment effects on glucose tolerance, lipid profiles, and plasma levels of leptin, adiponectin, ghrelin and C-reactive protein. Hypotheses will be evaluated by measuring 1) insulin action and secretion using frequently sampled intravenous glucose tolerance tests, 2) body composition using dual energy x-ray absorptiometry, magnetic resonance scans, and anthropomorphic measurements, and 3) changes in hormone levels and lipid profiles. The aims will be addressed in non-diabetic schizophrenia patients chronically treated with haloperidol, olanzapine or risperidone who will have valproate added to their treatment. Relevant data is critically needed to target basic research, identify long-term cardiovascular risks, and plan therapeutic interventions.
Detailed description
Schizophrenia is associated with increased rates of obesity, hyperglycemia, dyslipidemia and type 2 diabetes mellitus, causing increased morbidity and mortality due to acute (e.g., diabetic ketoacidosis) and long-term (e.g., vascular disease) complications. The association of type 2 diabetes and hyperglycemia with schizophrenia was first noted prior to the introduction of antipsychotic medications. However, additional glucoregulatory abnormalities, dyslipidemia, and increased adiposity have all been associated with antipsychotics. Risperidone and olanzapine are the most prescribed antipsychotics for schizophrenia in the U.S. In addition, schizophrenia patients in clinical practice are commonly treated with multi-class polypharmacy, with 35% of atypical antipsychotic prescriptions accompanied by co-prescription of valproate. This combination continues to increase in popularity, despite reports that the addition of valproate may further disturb glucose and lipid metabolism and weight regulation. While sensitive and validated measures of glucose and lipid metabolism and weight regulation are available, very few studies have addressed the metabolic consequences of this common type of polypharmacy.
This project aims to a) evaluate the effects of haloperidol, olanzapine, and risperidone in combination with valproate on insulin secretion and insulin actions, b) evaluate medication effects on abdominal fat, total body fat and total fat-free mass, and c) evaluate treatment effects on glucose tolerance, lipid profiles, and plasma levels of leptin, adiponectin, ghrelin and C-reactive protein. Hypotheses will be evaluated by measuring 1) insulin action and secretion using frequently sampled intravenous glucose tolerance tests, 2) body composition using dual energy x-ray absorptiometry, magnetic resonance scans, and anthropomorphic measurements, and 3) changes in hormone levels and lipid profiles. The aims will be addressed in non-diabetic schizophrenia patients chronically treated with haloperidol, olanzapine or risperidone who will have valproate added to their treatment. Relevant data is critically needed to target basic research, identify long-term cardiovascular risks, and plan therapeutic interventions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Schizophrenics | Active comparator | Drug: Depakote (valproate)i) meets DSM-IV criteria for schizophrenia, any type, treated with atypical or high potency typical neuroleptics for at least 3 months; ii) aged 18 to 60 years; iii) able to give informed consent; iv) no antipsychotic medication changes for 3 months, and no other medication changes for 2 weeks prior to Baseline Evaluations. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Meets DSM-IV criteria for schizophrenia, any type, treated with atypical or high potency typical neuroleptics for at least 3 months
- Aged 18 to 60 years
- 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 (9 listed)
- Meets DSM-IV criteria for the diagnoses of substance abuse or dependence within the past 6 months
- Involuntary legal status (as per Missouri law)
- The presence of any serious medical disorder that may (as confirmed by peer-reviewed literature) confound the assessment of symptoms, relevant biologic measures or diagnosis. The following conditions are currently identified:
- Meets DSM-IV criteria for Mental Retardation (mild or worse).
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 |
|---|---|---|
| Depakote (valproate)500 mg -2000 mg QD based on individual tolerance and VPA levels | Drug | Schizophrenics |
Primary outcome
Hypotheses will be evaluated by measuring insulin action and secretion using frequently sampled intravenous glucose tolerance tests
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2018.
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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.
Daniel W Haupt, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Depakote (valproate) in people with Insulin Resistance and Body Composition, run by Washington University School of Medicine at 1 site 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 4 inclusion and 9 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 21 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Hypotheses will be evaluated by measuring insulin action and secretion using frequently sampled intravenous glucose tolerance tests (time frame: 2 years). 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 21 Jun 2018.