SchizophreniaPhase 4NCT00337350
Rosiglitazone for Clozapine Induced Glucose Metabolism Impairment
A Phase 4 study testing rosiglitazone in people with Schizophrenia, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
We propose an eight-week, double-blind, placebo-controlled trial of rosiglitazone in schizophrenia subjects treated with clozapine using Bergman's Minimal Model (MINMOD) intravenous glucose tolerance test. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- rosiglitazone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2003to Jan 2011
- Phase
- Phase 4
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female
- Age 18-65 years
- Diagnosis of schizophrenia, any subtype, schizoaffective disorder, any subtype or schizophreniform disorder
- Well established compliance with out-patient medications
- Current treatment with clozapine for a minimum of one year
- Evidence of insulin resistance: impaired fasting glucose (glucose ≥100 mg/dl) or hyperinsulinemia (fasting insulin ≥ 15 ng/dl) or a HOMA-IR (homeostasis model assessment for insulin resistance) (fasting glucose X fasting insulin/22.5) ≥2 or a SI (insulin sensitivity index)
Who cannot join
- Inability to provide informed consent
- Current substance abuse
- Significant medical illness, including congestive heart failure, severe cardiovascular disease, renal disease (serum creatinine > 1.5), anemia (Hemoglobin < 11.0 gm/dL) or psychiatrically unstable
- Severe hepatic impairment, active liver disease or increased serum transaminase levels (ALT>2.0X upper limit of normal) If at any time, ALT increases to 2X ULN, the subject's participation in the study will be terminated.
- Women of child bearing potential who are pregnant, breastfeeding, or who are unwilling or unable to use an effective form of birth control during the entire study
- Treatment with agents that induce weight loss
Show all 10Show fewer
- History of diabetes mellitus or thyroid disease
- Current treatment with an oral hypoglycemic agent or insulin
- Known hypersensitivity to rosiglitazone or any of its components
- Fasting Glucose >126 mg/dL11. Treatment with other atypical antipsychotic agents thought to impair glucose metabolism (olanzapine) or low potency conventional agents (thioridazine, chlorpromazine)
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital Schizophrenia Program
Boston, Massachusetts, 02114
About this study
Official title: A Double-Blind, Placebo-Controlled Trial of Rosiglitazone for Clozapine Induced Glucose Metabolism Impairment: Bergman's Minimal Model Analysis
We propose an eight-week, double-blind, placebo-controlled trial of rosiglitazone in schizophrenia subjects treated with clozapine using Bergman's Minimal Model (MINMOD) intravenous glucose tolerance test. Bergman's 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.
Read the detailed description
This study is an eight-week, double-blind, placebo-controlled trial of rosiglitazone in schizophrenia subjects treated with clozapine using Bergman's 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 0.3 g/kg body weight will be infused. Approximately 35 2 cc blood samples will be withdrawn for measurement of glucose and insulin concentration. At minute 20, 0.05 units/kg 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 patient's 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.
- Conditions
- Schizophrenia
- Being tested
- rosiglitazone, placebo
- Keywords
- Schizophrenia, Glucose Metabolism, Insulin Resistance
- Medical subject headings
- Schizophrenia, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rosiglitazoneDrug
Rosiglitazone 4mg, one capsule per day for eight weeks
placeboDrug
matched placebo for rosiglitazone 4mg/day
| Study group | Role | What they receive |
|---|---|---|
| rosiglitazone | Active comparator | rosiglitazone 4mg/day Receives: Drug: rosiglitazone |
| placebo | Placebo comparator | matched placebo for 4mg rosiglitazone Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Insulin Sensitivity
Insulin Sensitivity (IS) was assessed using a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT), performed at Baseline and at week 8 (study endpoint). Subjects in the Rosiglitazone treatment arm were compared to subjects in the placebo treatment arm on their change in IS between Baseline and week 8. SI was calculated from plasma glucose and serum insulin values using the MINMOD Millennium computer program. SI represents the increase in net fractional glucose clearance rate per unit change in serum insulin concentration after the intravenous glucose load (microUnits/mL).
Measured: baseline, week 8
Change From Baseline on Glucose Utilization (SG)
Glucose utilization (SG) was assessed using a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT), performed at Baseline and at week 8 (study endpoint). Subjects in the Rosiglitazone treatment arm were compared to subjects in the placebo treatment arm on their change in SG between Baseline and week 8. SG was calculated from plasma glucose and serum insulin values using the MINMOD Millennium computer program. SG represents the net fractional glucose clearance rate because of the increase in glucose independent of any increase in circulating insulin concentrations above baseline.
Measured: baseline, week 8
Change From Baseline in Acute Insulin Response to Glucose (AIRG)
Acute insulin response to glucose (AIRG) was assessed using a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT), performed at Baseline and at week 8 (study endpoint). Subjects in the Rosiglitazone treatment arm were compared to subjects in the placebo treatment arm on their change in SG between Baseline and week 8. AIRG was calculated from plasma glucose and serum insulin values using the MINMOD Millennium computer program. AIRG measures the acute(0-10 min) beta\ cell response to a glucose load calculated by the areas under the curve higher than basal insulin values. The AIRG was assessed as the incremental area under the curve (calculated by the trapezoid rule) from 0 to 10 min of the FSIVGTT.
Measured: baseline, week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2006 (estimated)
- Study startSep 2003
- Primary completionJan 2011
- Study completionJan 2011
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.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression, Stanley Medical Research Institute
- Responsible party
- Principal investigator, David C. Henderson, Massachusetts General Hospital
- Investigators
- David C Henderson, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00337350
- Sponsor's protocol ID
- 2003-P-000014
- Status last verified
- Apr 2015
- First submitted
- 13 Jun 2006
- Last updated
- 8 May 2015
- Results posted
- Yes, on ClinicalTrials.gov
Publications
AMDISEN A. DRUG-PRODUCED OBESITY. EXPERIENCES WITH CHLORPROMAZINE, PERPHENAZINE AND CLOPENTHIXOL. Dan Med Bull. 1964 Oct;11:182-9. No abstract available.
PubMed 14209068Bergman RN. Lilly lecture 1989. Toward physiological understanding of glucose tolerance. Minimal-model approach. Diabetes. 1989 Dec;38(12):1512-27. doi: 10.2337/diab.38.12.1512.
PubMed 2684710Cohen S, Chiles J, MacNaughton A. Weight gain associated with clozapine. Am J Psychiatry. 1990 Apr;147(4):503-4. doi: 10.1176/ajp.147.4.503.
PubMed 2316740Cosway R, Strachan MW, Dougall A, Frier BM, Deary IJ. Cognitive function and information processing in type 2 diabetes. Diabet Med. 2001 Oct;18(10):803-10. doi: 10.1046/j.1464-5491.2001.00577.x.
PubMed 11678970Dwyer DS, Liu Y, Bradley RJ. Dopamine receptor antagonists modulate glucose uptake in rat pheochromocytoma (PC12) cells. Neurosci Lett. 1999 Oct 29;274(3):151-4. doi: 10.1016/s0304-3940(99)00712-0.
PubMed 10548412Dwyer DS, Pinkofsky HB, Liu Y, Bradley RJ. Antipsychotic drugs affect glucose uptake and the expression of glucose transporters in PC12 cells. Prog Neuropsychopharmacol Biol Psychiatry. 1999 Jan;23(1):69-80. doi: 10.1016/s0278-5846(98)00092-x.
PubMed 10368857Goldstein LE, Sporn J, Brown S, Kim H, Finkelstein J, Gaffey GK, Sachs G, Stern TA. New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment. Psychosomatics. 1999 Sep-Oct;40(5):438-43. doi: 10.1016/S0033-3182(99)71210-7. No abstract available.
PubMed 10479950Hagg S, Joelsson L, Mjorndal T, Spigset O, Oja G, Dahlqvist R. Prevalence of diabetes and impaired glucose tolerance in patients treated with clozapine compared with patients treated with conventional depot neuroleptic medications. J Clin Psychiatry. 1998 Jun;59(6):294-9. doi: 10.4088/jcp.v59n0604.
PubMed 9671341HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23(1):56-62. doi: 10.1136/jnnp.23.1.56. No abstract available.
PubMed 14399272Henderson DC, Cagliero E, Gray C, Nasrallah RA, Hayden DL, Schoenfeld DA, Goff DC. Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study. Am J Psychiatry. 2000 Jun;157(6):975-81. doi: 10.1176/appi.ajp.157.6.975.
PubMed 10831479Kay SR, Opler LA, Lindenmayer JP. Reliability and validity of the positive and negative syndrome scale for schizophrenics. Psychiatry Res. 1988 Jan;23(1):99-110. doi: 10.1016/0165-1781(88)90038-8.
PubMed 3363019Khandoudi N, Delerive P, Berrebi-Bertrand I, Buckingham RE, Staels B, Bril A. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma, inhibits the Jun NH(2)-terminal kinase/activating protein 1 pathway and protects the heart from ischemia/reperfusion injury. Diabetes. 2002 May;51(5):1507-14. doi: 10.2337/diabetes.51.5.1507.
PubMed 11978649Lamberti JS, Bellnier T, Schwarzkopf SB. Weight gain among schizophrenic patients treated with clozapine. Am J Psychiatry. 1992 May;149(5):689-90. doi: 10.1176/ajp.149.5.689.
PubMed 1349460Nuechterlein KH, Dawson ME, Gitlin M, Ventura J, Goldstein MJ, Snyder KS, Yee CM, Mintz J. Developmental Processes in Schizophrenic Disorders: longitudinal studies of vulnerability and stress. Schizophr Bull. 1992;18(3):387-425. doi: 10.1093/schbul/18.3.387.
PubMed 1411329Newcomer JW, Haupt DW, Fucetola R, Melson AK, Schweiger JA, Cooper BP, Selke G. Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry. 2002 Apr;59(4):337-45. doi: 10.1001/archpsyc.59.4.337.
PubMed 11926934
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo-Controlled Trial of Rosiglitazone for Clozapine Induced Glucose Metabolism Impairment: Bergman's Minimal Model Analysis
- ClinicalTrials.gov ID
- NCT00337350
- Acronym / sponsor ID
- 2003-P-000014
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, Glucose Metabolism, Insulin Resistance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression, Stanley Medical Research Institute
- Study start
- Sep 2003
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 15 Jun 2006 (estimated)
- Results
- Posted 6 Mar 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We propose an eight-week, double-blind, placebo-controlled trial of rosiglitazone in schizophrenia subjects treated with clozapine using Bergman's Minimal Model (MINMOD) intravenous glucose tolerance test. Bergman's 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 Bergman's 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 0.3 g/kg body weight will be infused. Approximately 35 2 cc blood samples will be withdrawn for measurement of glucose and insulin concentration. At minute 20, 0.05 units/kg 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 patient's 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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rosiglitazone | Active comparator | Drug: rosiglitazonerosiglitazone 4mg/day |
| placebo | Placebo comparator | Drug: placebomatched placebo for 4mg rosiglitazone |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female
- Age 18-65 years
- Diagnosis of schizophrenia, any subtype, schizoaffective disorder, any subtype or schizophreniform disorder
- Well established compliance with out-patient medications
- Current treatment with clozapine for a minimum of one year
Key exclusion criteria (10 listed)
- Inability to provide informed consent
- Current substance abuse
- Significant medical illness, including congestive heart failure, severe cardiovascular disease, renal disease (serum creatinine > 1.5), anemia (Hemoglobin < 11.0 gm/dL) or psychiatrically unstable
- Severe hepatic impairment, active liver disease or increased serum transaminase levels (ALT>2.0X upper limit of normal) If at any time, ALT increases to 2X ULN, the subject's participation in the study will be terminated.
- Women of child bearing potential who are pregnant, breastfeeding, or who are unwilling or unable to use an effective form of birth control during the entire study
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 |
|---|---|---|
| rosiglitazoneRosiglitazone 4mg, one capsule per day for eight weeks | Drug | rosiglitazone |
| placebomatched placebo for rosiglitazone 4mg/day | Drug | placebo |
Primary outcome
Change From Baseline in Insulin Sensitivity
Time frame: baseline, week 8
Insulin Sensitivity (IS) was assessed using a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT), performed at Baseline and at week 8 (study endpoint). Subjects in the Rosiglitazone treatment arm were compared to subjects in the placebo treatment arm on their change in IS between Baseline and week 8. SI was calculated from plasma glucose and serum insulin values using the MINMOD Millennium computer program. SI represents the increase in net fractional glucose clearance rate per unit change in serum insulin concentration after the intravenous glucose load (microUnits/mL).
Change From Baseline on Glucose Utilization (SG)
Time frame: baseline, week 8
Glucose utilization (SG) was assessed using a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT), performed at Baseline and at week 8 (study endpoint). Subjects in the Rosiglitazone treatment arm were compared to subjects in the placebo treatment arm on their change in SG between Baseline and week 8. SG was calculated from plasma glucose and serum insulin values using the MINMOD Millennium computer program. SG represents the net fractional glucose clearance rate because of the increase in glucose independent of any increase in circulating insulin concentrations above baseline.
Change From Baseline in Acute Insulin Response to Glucose (AIRG)
Time frame: baseline, week 8
Acute insulin response to glucose (AIRG) was assessed using a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT), performed at Baseline and at week 8 (study endpoint). Subjects in the Rosiglitazone treatment arm were compared to subjects in the placebo treatment arm on their change in SG between Baseline and week 8. AIRG was calculated from plasma glucose and serum insulin values using the MINMOD Millennium computer program. AIRG measures the acute(0-10 min) beta\ cell response to a glucose load calculated by the areas under the curve higher than basal insulin values. The AIRG was assessed as the incremental area under the curve (calculated by the trapezoid rule) from 0 to 10 min of the FSIVGTT.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 14209068AMDISEN A. DRUG-PRODUCED OBESITY. EXPERIENCES WITH CHLORPROMAZINE, PERPHENAZINE AND CLOPENTHIXOL. Dan Med Bull. 1964 Oct;11:182-9. No abstract available.
- Background: PubMed 2684710Bergman RN. Lilly lecture 1989. Toward physiological understanding of glucose tolerance. Minimal-model approach. Diabetes. 1989 Dec;38(12):1512-27. doi: 10.2337/diab.38.12.1512.
- Background: PubMed 2316740Cohen S, Chiles J, MacNaughton A. Weight gain associated with clozapine. Am J Psychiatry. 1990 Apr;147(4):503-4. doi: 10.1176/ajp.147.4.503.
- Background: PubMed 11678970Cosway R, Strachan MW, Dougall A, Frier BM, Deary IJ. Cognitive function and information processing in type 2 diabetes. Diabet Med. 2001 Oct;18(10):803-10. doi: 10.1046/j.1464-5491.2001.00577.x.
- Background: PubMed 10548412Dwyer DS, Liu Y, Bradley RJ. Dopamine receptor antagonists modulate glucose uptake in rat pheochromocytoma (PC12) cells. Neurosci Lett. 1999 Oct 29;274(3):151-4. doi: 10.1016/s0304-3940(99)00712-0.
- Background: PubMed 10368857Dwyer DS, Pinkofsky HB, Liu Y, Bradley RJ. Antipsychotic drugs affect glucose uptake and the expression of glucose transporters in PC12 cells. Prog Neuropsychopharmacol Biol Psychiatry. 1999 Jan;23(1):69-80. doi: 10.1016/s0278-5846(98)00092-x.
- Background: PubMed 10479950Goldstein LE, Sporn J, Brown S, Kim H, Finkelstein J, Gaffey GK, Sachs G, Stern TA. New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment. Psychosomatics. 1999 Sep-Oct;40(5):438-43. doi: 10.1016/S0033-3182(99)71210-7. No abstract available.
- Background: PubMed 9671341Hagg S, Joelsson L, Mjorndal T, Spigset O, Oja G, Dahlqvist R. Prevalence of diabetes and impaired glucose tolerance in patients treated with clozapine compared with patients treated with conventional depot neuroleptic medications. J Clin Psychiatry. 1998 Jun;59(6):294-9. doi: 10.4088/jcp.v59n0604.
- Background: PubMed 14399272HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23(1):56-62. doi: 10.1136/jnnp.23.1.56. No abstract available.
- Background: PubMed 10831479Henderson DC, Cagliero E, Gray C, Nasrallah RA, Hayden DL, Schoenfeld DA, Goff DC. Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study. Am J Psychiatry. 2000 Jun;157(6):975-81. doi: 10.1176/appi.ajp.157.6.975.
- Background: PubMed 3363019Kay SR, Opler LA, Lindenmayer JP. Reliability and validity of the positive and negative syndrome scale for schizophrenics. Psychiatry Res. 1988 Jan;23(1):99-110. doi: 10.1016/0165-1781(88)90038-8.
- Background: PubMed 11978649Khandoudi N, Delerive P, Berrebi-Bertrand I, Buckingham RE, Staels B, Bril A. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma, inhibits the Jun NH(2)-terminal kinase/activating protein 1 pathway and protects the heart from ischemia/reperfusion injury. Diabetes. 2002 May;51(5):1507-14. doi: 10.2337/diabetes.51.5.1507.
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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.
David C Henderson, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing rosiglitazone in people with Schizophrenia, run by Massachusetts General Hospital 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 6 inclusion and 10 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 8 May 2015. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Mar 2013). 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?
Change From Baseline in Insulin Sensitivity (time frame: baseline, week 8). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00337350, which also lists 24 linked publications.
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 8 May 2015.