Clinical trial NCT00480844: Comparison of Cognitive Functions of Schizophrenic Patients Treated With Sertindole Versus Risperidone
Official title: Comparison of Cognitive Functions of Schizophrenic Patients Treated With Sertindole Versus Risperidone
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Schizophrenia
Keywords: schizophrenia
Sertindole
Risperidone
cognitive impairment
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2007-05-31
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this study we intend to compare the effect of Sertindole to that of Risperidone on cognitive impairment in schizophrenia.

Hypothesis: Sertindole will be as effective as Risperidone for treating cognitive impairment in schizophrenia and with fewer side effects.

Detailed description: Introduction:

In this proposal we intend to compare the effect of Sertindole to that of Risperidone on cognitive impairment in schizophrenia.

Hypothesis:

Sertindole will be as effective as Risperidone for treating cognitive impairment in schizophrenia and with fewer side effects.

Study Drugs:

Risperidone is an "atypical" antipsychotic drug, being used widely all over the world. In Israel, Risperidone has been the first line drug for schizophrenia at the past decade. This drug was shown to be efficacious with bearable side effects. The side effects include: tiredness, dizziness, muscle dystonia, increased appetite and weight, dry mouth, constipation, tremor, orthostatic hypotension.

Sertindole is another "atypical" antipsychotic drug. The drug has been approved by the Israeli Ministry of Health. Sertindole was initially marketed in Britain on 1996. It was taken off the market, following several reports of cardiovascular deaths suspected to be caused by the drug (i.e. prolongation of the QT-interval in the ECG, suspected to cause ventricular arrhythmias). After renewing research, investigating more then 10000 patients for several years, the drug was found to be as safe as other antipsychotics. On 2002, the European union decided to put the Sertindole to the market.

Common Sertindole side effects are: dizziness, parasthesias, edema, orthostatic hypotension, nasal congestion, dyspnea, dry mouth, decreased semen volume, increased weight, prolongation of QT-interval in ECG.

Subjects and methods:

Overview: We propose to perform a multi-center, randomized, parallel-group, open-label study administering Sertindole or Risperidone to patients with schizophrenia, N=60. The primary outcome measure will be cognitive functioning. Secondary outcome measures will be discontinuation due to all causes, symptomatology and adverse events.

Procedure and Instruments:

Subjects:

Sixty male and female subjects will be recruited from patients treated in the inpatient and outpatient units in the Department of Psychiatry of the Sheba Medical Center, the Beer-Yaakov Mental Health Center and the Kfar Shaul Mental Health Center. Before inclusion into the study, patients will receive a careful medical workup, including complete medical history, physical examination; routine blood chemistry and blood count, EKG and urinalysis.

Inclusion and exclusion criteria will be based on the SmPCs of both compounds.

Medication:

The doses of study medication used will be based on the doses currently recommended by the manufacturers: Sertindole: 16-20 mg/day (in exceptional cases subjects will receive 24 mg/day, based on the clinical reasoning) or Risperidone 4-8 mg/day.

Duration:

Duration of randomized, open-label treatment will be 12 weeks. Following this phase, an additional 12 week phase with Sertindole will be offered to subjects who were previously randomized to the Risperidone arm.. As per IRB requirements, patients responding to Sertindole will be eligible to receive Sertindole as compassionate care(in accordance wit MOH requirements for compassionate care)

Assessment instruments:

* the following assessment scales will be administered before randomization, after 12 weeks of randomized treatment, and , if applicable, following 12 weeks of with Sertindole Positive symptoms will be assessed by PANSS (Positive and Negative Syndrome Scale)
* Negative symptoms will be assessed by SANS (Scale of the Assessment of Negative Symptoms)
* Cognitive functioning will be assessed using MATRICS (Measurement And Treatment Research to Improve Cognition in Schizophrenia).
* Movement disorders will be assessed by the Simpson Angus Scale and AIMS (Abnormal Involuntary Movement Scale) scales
* Blood levels of glucose, triglycerides and cholesterol
* Weight, height, and vital signs will be measured and recorded
* ECG

Tests which are language-sensitive have been standardized and will be in assessed in Hebrew. Assessment will be made by a rater who is blinded to the treatment.

Concomitant Medications:

Patients receiving mood-stabilizers, anti-depressants, sedatives and hypnotics will be allowed to participate in the study only if they are on a stable dose of these medications for 2 weeks before entering the trial. After randomization, changes in the doses of concomitant medications will be recorded and analyzed at the end of the study.

Eligibility criteria: Inclusion Criteria:

* Patients suffering from Schizophrenia (DSM IV).
* Failure of at least one previous antipsychotic for intolerance.
* Psychotic symptoms that are not secondary to a general medical condition or substance abuse.
* Ages between 18-65 years old.
* Patients receiving other psychotropic medications (anti-depressants, mood stabilizers, sedatives, hypnotics) must be on a stable dose for at least 2 weeks before entering the trial.
* Able to understand and sign an informed consent form.

Exclusion Criteria:

* Patients suffering from psychotic disorders caused by a general medical condition.
* Patients having high suicidal risk, as measured by score of 2 or more in CDSS - Calgary Depression Scale for Schizophrenia.
* Patients suffering from an unstable clinically significant medical condition (endocrine, nutritional, hepatic, urinary).
* Significant cardiovascular illness, and/or QT prolongation at screening (more then 450 msec for male or 470 msec for female).
* Patients suffering from a malignancy or neuro-degenerative illness (e.g. Parkinsons' Disease)
* Patients suffering from organic brain disorders, including epilepsy and mental retardation.
* Patients suffering from a clinically significant mood disorder.
* Pregnancy.
* History of drug or alcohol dependence within the last year.
* Previous documented non-response to Risperidone.
* Patients using medicinal products that are contraindicated with sertindole and/or Risperidone.

Primary outcomes:
measure: cognitive functioning
timeFrame: 24 weeks
Secondary outcomes:
measure: Discontinuation due to all causes, symptomatology and adverse events.
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: Department of Psychiatry of the Sheba Medical Center
state: Tel Hashomer
city: Beer-Yaakov
country: Israel
facility: Beer-Yaakov Mental Health Center
city: Jerusalem
country: Israel
facility: Kfar Shaul Mental Health Center
Study officials:
affiliation: Shaba Medical Center, Tel-Aviv University Sackler School of Medicine
name: Mark Weiser, Dr
role: PRINCIPAL_INVESTIGATOR
References: