Ignite Creation Date:
2024-05-05 @ 4:52 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00337350
Status:
COMPLETED
Last Update Posted:
2015-05-08
First Post:
2006-06-13
Brief Title:
Rosiglitazone for Clozapine Induced Glucose Metabolism Impairment
Sponsor:
Massachusetts General Hospital
Organization:
Massachusetts General Hospital
Study Overview
Official Title:
A Double-Blind Placebo-Controlled Trial of Rosiglitazone for Clozapine Induced Glucose Metabolism Impairment Bergmans Minimal Model Analysis
Status:
COMPLETED
Status Verified Date:
2015-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
We propose an eight-week double-blind placebo-controlled trial of rosiglitazone in schizophrenia subjects treated with clozapine using Bergmans Minimal Model MINMOD intravenous glucose tolerance test Bergmans Minimal Model analysis with frequent sampled intravenous glucose tolerance test FSIVGTT provides a sensitive and reliable method to measure glucose effectiveness insulin secretion and insulin sensitivity The MINMOD determines the relationship between insulin sensitivity insulin secretion and the degree of obesity and can be used to study drug effects upon these variables
Detailed Description:
This study is an eight-week double-blind placebo-controlled trial of rosiglitazone in schizophrenia subjects treated with clozapine using Bergmans Minimal Model Analysis MINMOD frequent sampled intravenous glucose tolerance test FSIVGTT for examination of glucose metabolism Rosiglitazone used for the treatment of type 2 diabetes improves glycemic control by improving insulin sensitivity in target tissues while increase glucose uptake and improving signaling between insulin and glucose transporters The MINMOD determines the relationship between insulin sensitivity insulin secretion and the degree of obesity and can be used to study drug effects upon these variables The computer program estimates glucose effectiveness SG insulin sensitivity SI and the acute insulin response to glucose AIRG from glucose and insulin values measured during the FSIVGTT
The site for subject enrollment clinical assessment and collection of blood samples at weeks 2 4 and 6 will be at the Freedom Trail Clinic of the Erich Lindemann Mental Health Center The FSIVGTT and blood samples at baseline and week 8 will be conducted at the Mallinckrodt General Clinical Research Center at Massachusetts General Hospital Subjects will include 50 clozapine treated patients with the diagnosis of schizophrenia or schizoaffective disorder Subjects will be matched according to baseline fasting glucose
Subjects will be maintained on their pre-study medication During the baseline assessment a member of the research team will conduct the PANSS Positive and Negative Symptom Subscale and HAM-D Hamilton Rating Scale for Depression which will be repeated at weeks 4 and 8 to determine baseline and subsequent changes in psychopathology The neuropsychological battery will be administered at baseline and week 8 and will consist of North America Adult Reading Test Trail Making Degraded Stimulus Continuous Performance Test California Verbal Learning Test Faces and Family Picture subtests from WMS-III Wisconsin Card Sorting Test Letter and Category Fluency Letter-Number Sequencing and Grooved Peg Board Baseline medical evaluation will include weight height vital signs AIMS score a 12-lead EKG and a physical examination
Subjects will be instructed to eat a diet high in carbohydrates for three days before the FSIVGTT They are instructed to fast for 12 hours preceding the test On the morning of the test subjects will be admitted to the General Clinical Research Center at Massachusetts General Hospital A nutritional assessment will be performed Baseline blood samples for fasting glucose basic chemistry profiles liver enzymes complete blood count cbc insulin prolactin lipid profile glycohemoglobin leptin clozapine serum levels and cortisol will be drawn Glucose 03 gkg body weight will be infused Approximately 35 2 cc blood samples will be withdrawn for measurement of glucose and insulin concentration At minute 20 005 unitskg of insulin will be administered as an intravenous bolus injection
Following baseline FSIVGTT subjects will be randomized double-blind to either rosiglitazone or placebo Subjects randomized to receive medication will receive rosiglitazone 4mg po qd for eight weeks or until study end Subjects will be monitored for symptoms of diabetes at weeks 2 4 and 8 Subjects will be evaluated at weeks 2 4 and 8 including measurements of blood pressure pulse and weight Adverse events will be monitored at weeks 2 4 and 8 with the AMDP-5 a survey of side effects and somatic symptoms The Medical Outcomes Study Short Form-12 SF-12 will be used to measure general health status and function The SF-12 will be performed at baseline weeks 4 and 8 or study end
A cbc will be performed every two weeks consistent with the requirements for treatment with clozapine At week four a fasting glucose insulin level and liver function tests will be performed At the end of the eighth week the FSIVGTT will be repeated and blood samples will be obtained for fasting glucose basic chemistry profiles liver enzymes complete blood count cbc insulin prolactin lipid profile glycohemoglobin leptin clozapine serum levels and cortisol All other aspects of the subjects care will be treatment as usual
Potential risks associated with an intravenous line include bruising at the site bleeding and the risk of infection During the procedure patient may experience symptoms of low blood glucose including lightheadedness dizziness weakness irritability sweating tremor tachycardia anxiety and hunger The amount of blood drawn with each FSIVGTT is approximately 150 cc A low risk of anemia exists secondary to the FSIVGTT anemia has also been a side effect of treatment with rosiglitazone Treatment with rosiglitazone has been associated with side effects including accidental injury cuts and abrasions headache back pain anemia edema weight gain decreased white blood cell count increases in total cholesterol LDL and HDL and decreases in free fatty acids Phlebotomy may produce discomfort bruising and rarely infection While the clinical assessment may be stressful the questions contained in the SCID and PANSS do not differ from those asked in routine clinical evaluations
Potential benefits to the subject include a comprehensive diagnostic re-evaluation screening blood tests and estimation of risk of diabetes The results of the tests will be shared with patients and clinicians and may contribute to medical management by helping the patients physician in deciding if an intervention is required to reduce the risk of diabetes An increased understanding of the process by which clozapine induces glucose intolerance and the awareness that diabetes and its complications can be prevented with concomitant treatment with an insulin sensitizer are potential benefits to this population
The site for subject enrollment clinical assessment and collection of blood samples at weeks 2 4 and 6 will be at the Freedom Trail Clinic of the Erich Lindemann Mental Health Center The FSIVGTT and blood samples at baseline and week 8 will be conducted at the Mallinckrodt General Clinical Research Center at Massachusetts General Hospital Subjects will include 50 clozapine treated patients with the diagnosis of schizophrenia or schizoaffective disorder Subjects will be matched according to baseline fasting glucose
Subjects will be maintained on their pre-study medication During the baseline assessment a member of the research team will conduct the PANSS Positive and Negative Symptom Subscale and HAM-D Hamilton Rating Scale for Depression which will be repeated at weeks 4 and 8 to determine baseline and subsequent changes in psychopathology The neuropsychological battery will be administered at baseline and week 8 and will consist of North America Adult Reading Test Trail Making Degraded Stimulus Continuous Performance Test California Verbal Learning Test Faces and Family Picture subtests from WMS-III Wisconsin Card Sorting Test Letter and Category Fluency Letter-Number Sequencing and Grooved Peg Board Baseline medical evaluation will include weight height vital signs AIMS score a 12-lead EKG and a physical examination
Subjects will be instructed to eat a diet high in carbohydrates for three days before the FSIVGTT They are instructed to fast for 12 hours preceding the test On the morning of the test subjects will be admitted to the General Clinical Research Center at Massachusetts General Hospital A nutritional assessment will be performed Baseline blood samples for fasting glucose basic chemistry profiles liver enzymes complete blood count cbc insulin prolactin lipid profile glycohemoglobin leptin clozapine serum levels and cortisol will be drawn Glucose 03 gkg body weight will be infused Approximately 35 2 cc blood samples will be withdrawn for measurement of glucose and insulin concentration At minute 20 005 unitskg of insulin will be administered as an intravenous bolus injection
Following baseline FSIVGTT subjects will be randomized double-blind to either rosiglitazone or placebo Subjects randomized to receive medication will receive rosiglitazone 4mg po qd for eight weeks or until study end Subjects will be monitored for symptoms of diabetes at weeks 2 4 and 8 Subjects will be evaluated at weeks 2 4 and 8 including measurements of blood pressure pulse and weight Adverse events will be monitored at weeks 2 4 and 8 with the AMDP-5 a survey of side effects and somatic symptoms The Medical Outcomes Study Short Form-12 SF-12 will be used to measure general health status and function The SF-12 will be performed at baseline weeks 4 and 8 or study end
A cbc will be performed every two weeks consistent with the requirements for treatment with clozapine At week four a fasting glucose insulin level and liver function tests will be performed At the end of the eighth week the FSIVGTT will be repeated and blood samples will be obtained for fasting glucose basic chemistry profiles liver enzymes complete blood count cbc insulin prolactin lipid profile glycohemoglobin leptin clozapine serum levels and cortisol All other aspects of the subjects care will be treatment as usual
Potential risks associated with an intravenous line include bruising at the site bleeding and the risk of infection During the procedure patient may experience symptoms of low blood glucose including lightheadedness dizziness weakness irritability sweating tremor tachycardia anxiety and hunger The amount of blood drawn with each FSIVGTT is approximately 150 cc A low risk of anemia exists secondary to the FSIVGTT anemia has also been a side effect of treatment with rosiglitazone Treatment with rosiglitazone has been associated with side effects including accidental injury cuts and abrasions headache back pain anemia edema weight gain decreased white blood cell count increases in total cholesterol LDL and HDL and decreases in free fatty acids Phlebotomy may produce discomfort bruising and rarely infection While the clinical assessment may be stressful the questions contained in the SCID and PANSS do not differ from those asked in routine clinical evaluations
Potential benefits to the subject include a comprehensive diagnostic re-evaluation screening blood tests and estimation of risk of diabetes The results of the tests will be shared with patients and clinicians and may contribute to medical management by helping the patients physician in deciding if an intervention is required to reduce the risk of diabetes An increased understanding of the process by which clozapine induces glucose intolerance and the awareness that diabetes and its complications can be prevented with concomitant treatment with an insulin sensitizer are potential benefits to this population
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None