Schizophrenia
Conditions
Keywords
Polysomnograph
Brief summary
This study will apply polysomnography (PSG) to evaluate the effect of quetiapine fumarate on sleep architecture. Most of previous studies evaluated sleep by self-reported questionnaires during the antipsychotic treatment (clozapine, risperidone, olanzapine, et al), while only a few studies with PSG evaluation had some limitation, such as: small sample size, respective or cross-sectional, potential sleep disorders, et al. In this study, we will investigate both subjective and objective effect of quetiapine fumarate in improving sleep quality in schizophrenic patients by PSG as well as psychiatric scales. The control drug in this study is the typical antipsychotic - haloperidol. It could increase sleep duration and efficiency by mostly increasing the S2 without effect on rapid eye movement (REM) sleep and slow wave sleep (SWS). The patients will be randomised into two groups as a parallel design. This study is designed as rater blinded to reduce the bias in evaluation. It is suggested that the sedative effect of quetiapine fumarate could diminish in 2 weeks, therefore, we use 4 weeks to ensure the change of sleep quality in this study, which could be helpful for the evaluation of relative short and middle term effect of quetiapine fumarate on sleep quality.
Detailed description
1. The objective sleep structures of quetiapine fumarate and haloperidol being used as mono-therapy respectively in the treatment of patients with acute schizophrenia are measured by the change of composite variables for PSG test (sleep stages, time in bed, total sleep time, sleep efficiency, sleep latency) from baseline to Week 4 (LOCF). 2. The subjective sleep qualities of quetiapine fumarate and haloperidol being used as mono-therapy respectively in the treatment of patients with acute schizophrenia are measured by the change of Pittsburgh Sleep Quality Inventory (PSQI) and Epworth Sleepiness Scale(ESS) from baseline to Week 4 (LOCF). 3. The clinical efficacy of quetiapine fumarate and haloperidol being used as mono-therapy respectively in the treatment of patients with acute schizophrenia are measured by the change of Positive and Negative Syndrome Scale (PANSS) and Clinical Globe Impression (CGI),and Calgary Depression Scale for Schizophrenia (CDSS) from baseline to Week 4 (LOCF). 4. The clinical safety and tolerance quetiapine fumarate and haloperidol being used as mono-therapy respectively in the treatment of patients with acute schizophrenia are measured by Treatment Emergent Symptom Scale (TESS) in day 14 and day 28.
Interventions
DRUGquetiapine fumarate
600-750mg/day
DRUGhaloperidol
6-40mg/day
Sponsors
Guang Dong Provincial Mental Health Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
For inclusion in the study patients must fulfill all of the following criteria: 1. Provision of written informed consent by patient or his/her legal guardian 2. Hospitalized for a diagnosis of Schizophrenia paranoid subtype by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV) 3. Positive and Negative Syndrome Scale (PANSS) total score≥60 4. Female patients of childbearing potential must be using a reliable method of contraception and have a negative urine human chronic gonadotropin (HCG) test at enrolment 5. Able to understand and comply with the requirements of the study
Exclusion criteria
Any of the following is regarded as a criterion for exclusion from the study: 1. Pregnancy or lactation 2. Any DSM-IV Axis I disorder not defined in the inclusion criteria 3. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others 4. Known intolerance or lack of response to quetiapine fumarate or/and haloperidol, as judged by the investigator 5. Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir 6. Use of any of the following cytochrome P450 3A4 inducers in the 14 days preceding enrolment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids 7. Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation 8. Substance or alcohol dependence at enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria 9. Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrolment 10. Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment 11. Unstable or inadequately treated medical illness (e.g. congestive heart failure, angina pectoris, hypertension) as judged by the investigator 12. Organic changes was founded by brain CT 13. Involvement in the planning and conduct of the study 14. Previous enrolment or randomisation of treatment in the present study. 15. Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements 16. A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria: unstable DM defined as enrolment glycosylated hemoglobin (HbA1c) \>8.5%; admitted to hospital for treatment of DM or DM related illness in past 12 weeks; not under physician care for DM Physician responsible for patient's DM care has not indicated that patient's DM is controlled; Physician responsible for patient's DM care has not approved patient's participation in the study; has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to randomisation; for thiazolidinediones (glitazones) this period should not be less than 8 Weeks; taking insulin whose daily dose on one occasion in the past 4 weeks has been more than 10% above or below their mean dose in the preceding 4 weeks. Note: If a diabetic patient meets one of these criteria, the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study. 17. An absolute neutrophil count (ANC) of 1.5 x 109/L 18. Sleep disorder such as Apnea Hypopneas Syndrome, periodic leg movement syndrome and narcolepsy 19. The work time is rotate and/or often flies across the time zone 20. Use of clozapine within 28 days prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Slow Wave Sleep | 28 days | The primary variable is the change of percentage of slow wave sleep (SWS) from baseline to the 28th day (LOCF). |
| Percentage of Rapid Eye Movement Sleep | 28 days | The primary variable is the change of the percentage of rapid eye movement (REM)sleep from baseline to the 28th day (LOCF). |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Quetiapine Fumarate quetiapine fumarate treatment (200-750mg/day) in 28 days | 30 |
| Haloperidol haloperidol treatment (6-40mg/day) in 28 days | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Lack of Efficacy | 2 | 2 |
| Overall Study | misdiagnosis | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Haloperidol | Quetiapine Fumarate | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 3 Participants | 5 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 27 Participants | 55 Participants |
| Age, Continuous | 27.9 years STANDARD_DEVIATION 6.7 | 25.0 years STANDARD_DEVIATION 10.1 | 26.3 years STANDARD_DEVIATION 8.2 |
| Region of Enrollment China | 30 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 17 Participants | 20 Participants | 37 Participants |
| Sex: Female, Male Male | 13 Participants | 10 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Percentage of Rapid Eye Movement Sleep
The primary variable is the change of the percentage of rapid eye movement (REM)sleep from baseline to the 28th day (LOCF).
Time frame: 28 days
Population: For the need of the statistical analysis, the study group and the control group are 30 evaluable patients respectively. Finally, in consideration of 25% un-evaluable patients after randomisation, there should be 80 patients randomised in this study with 40 patients per arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Quetiapine Fumarate | Percentage of Rapid Eye Movement Sleep | percentage at baseline | 12.6 percentage of rapid eye movement sleep | Standard Deviation 9.1 |
| Quetiapine Fumarate | Percentage of Rapid Eye Movement Sleep | percentage on the 28th day | 16.4 percentage of rapid eye movement sleep | Standard Deviation 9.2 |
| Quetiapine Fumarate | Percentage of Rapid Eye Movement Sleep | percentage change from baseline to the 28th day | 3.9 percentage of rapid eye movement sleep | Standard Deviation 3.2 |
| Haloperidol | Percentage of Rapid Eye Movement Sleep | percentage at baseline | 13.2 percentage of rapid eye movement sleep | Standard Deviation 5.3 |
| Haloperidol | Percentage of Rapid Eye Movement Sleep | percentage on the 28th day | 10.4 percentage of rapid eye movement sleep | Standard Deviation 11.3 |
| Haloperidol | Percentage of Rapid Eye Movement Sleep | percentage change from baseline to the 28th day | -2.7 percentage of rapid eye movement sleep | Standard Deviation 2.5 |
Primary
Percentage of Slow Wave Sleep
The primary variable is the change of percentage of slow wave sleep (SWS) from baseline to the 28th day (LOCF).
Time frame: 28 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Quetiapine Fumarate | Percentage of Slow Wave Sleep | percentage at baseline | 10.5 percentage of slow wave sleep | Standard Deviation 5.5 |
| Quetiapine Fumarate | Percentage of Slow Wave Sleep | percentage on the 28th day | 9.2 percentage of slow wave sleep | Standard Deviation 8 |
| Quetiapine Fumarate | Percentage of Slow Wave Sleep | percentage change from baseline to the 28th day | -1.4 percentage of slow wave sleep | Standard Deviation 1.1 |
| Haloperidol | Percentage of Slow Wave Sleep | percentage at baseline | 8.6 percentage of slow wave sleep | Standard Deviation 7.6 |
| Haloperidol | Percentage of Slow Wave Sleep | percentage on the 28th day | 6.3 percentage of slow wave sleep | Standard Deviation 5.4 |
| Haloperidol | Percentage of Slow Wave Sleep | percentage change from baseline to the 28th day | -2.3 percentage of slow wave sleep | Standard Deviation 1.8 |