A 4-Week, Randomized, Rater-Blinded, Parallel Study to Evaluate Quetiapine in Improving Sleep Quality of Schizophrenia

Sleep disorders have been recognized by psychiatrists as a range of important symptoms of schizophrenia, which often appear in the exacerbation period as a signal of relapse and increase the risk of suicide. It could be very helpful for the management and prognosis of schizophrenia by a drug that could improve the sleep without over-sedation.

Quetiapine fumarate is a newer atypical antipsychotic with good tolerability. Although sedative effect is common, it will diminish in two weeks without dose adjustment. However, there is no systemic PSG study to investigate the effect of quetiapine on sleep quantity and quality. The systematic PSG study will be helpful to explore such clinical problems as:

increasing sleep duration or not, improving the sleep quality by influencing SWS and REM or not, the effect of quetiapine on sleep relating to the prognosis of the positive and negative symptoms or not, and so on.

Since it had the major effect on the 5-HT2A and little effect on 5-HT2C in the 5-HT2 system, quetiapine might not improve the sleep quality by increasing SWS. However, another study on patients with schizophrenia suggested quetiapine could increase SWS duration. It might due to the difference of neurobiological condition between the patients with schizophrenia and the health volunteers. We hypothesized that quetiapine might increase SWS duration in schizophrenia through modifying the neurobiological pathological mechanism.

Intervention(s) in this Clinical Trial

• Drug: quetiapine fumarate
  • quetiapine fumarate: 600-750mg/day
• Drug: haloperidol
  • haloperidol: 6-40mg/day

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • quetiapine fumarate
• Active Comparator: 2
  • haloperidol

Primary Measures

• The primary objective is to evaluate the effect of quetiapine fumarate on sleep structures as mono-therapy in the treatment of patients with acute schizophrenia.
  • Time Frame: 28 days
    Safety Issue?: Yes

Secondary Measures

• The efficacy of quetiapine as mono-therapy in improving sleep quality in acute schizophrenia
  • Time Frame: 28 days
    Safety Issue?: Yes
• The efficacy of quetiapine as mono-therapy in acute schizophrenia
  • Time Frame: 28 days
    Safety Issue?: Yes
• The safety and tolerability of quetiapine as mono-therapy in acute schizophrenia
  • Time Frame: 28 days
    Safety Issue?: Yes

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. 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, PLMS 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Guang Dong Provincial Mental Health Institute Other

Overall Clinical Trial Officials and Contacts

Zhang Bin, Ph. D Principal Investigator Guang Dong Provincial Mental Health Institute  

Overall Contact: Bin Zhang, Ph.D 8620-81884713 zhang73bin@yahoo.com.cn

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00642369

Study ID Number: D1443L00053

ClinicalTrials.gov Identifier: NCT00642369

Health Authority: China: Ethics Committee