Effectiveness of Tropisetron Plus Risperidone for Improving Cognitive and Perceptual Disturbances in Schizophrenia

Study Overview
=================
Brief Summary
-----------------
This study will determine the effectiveness of tropisetron plus risperidone in improving cognitive symptoms in Chinese people with schizophrenia.

Detailed Description
-----------------
Schizophrenia is a chronic and disabling brain disorder. People with schizophrenia may experience hallucinations, delusions, disordered thinking, movement disorders, social withdrawal, and cognitive deficits. In considering the high rate of cigarette smoking among people with schizophrenia, it is also likely that they smoke. People with schizophrenia who smoke tend to experience improved cognition, and tobacco withdrawal has been associated with deterioration of cognition. This suggests that nicotine may improve cognitive deficits or medication side effects in people with schizophrenia. Auditory sensory gating, a neural mechanism thought to reflect sensory information processing and affect cognition, is diminished in people with schizophrenia. Auditory sensory gating has been associated with the 7 nicotinic acetylcholine receptor, a brain receptor that is important for cognition and can be activated by nicotine. Activation of this receptor using an agonist medication, such as tropisetron, may produce the same positive effect that nicotine has on cognition. This study will determine the effectiveness of using tropisetron as supplemental therapy to the atypical neuroleptic risperidone in people with schizophrenia. Participants in this 12-week double blind study will be randomly assigned to receive either tropisetron or placebo. All participants will also follow a 6-mg risperidone regimen. Study visits will occur every 2 weeks throughout the study and final outcome assessments will include cognitive functioning and treatment safety and effectiveness.

Official Title
-----------------
Tropisetron With Risperidone for Schizophrenia

Conditions
-----------------
Smoking Cessation, Schizophrenia

Intervention / Treatment
-----------------
* Drug: Tropisetron
* Drug: Placebo
* Drug: Risperidone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Currently resides in Beijing, China Diagnosis of schizophrenia or schizophreniform disorder Duration of symptoms is no longer than 60 months No history of treatment with antipsychotic medication or, if previously treated, a total lifetime usage of less than 14 days Current psychotic symptoms are of moderate severity or greater as measured by one of the five psychotic items in the Brief Psychiatric Rating Scale (BPRS) Exclusion Criteria: Diagnostic and Statistical Manual of Mental Disorders(DSM)-IV Axis I diagnosis other than schizophrenia or schizophreniform psychosis Documented disease of the central nervous system that might interfere with the trial assessments (e.g., stroke, tumor, Parkinson's disease, Huntington's disease, seizure disorder, history of brain trauma resulting in significant impairment, chronic infection) Acute, unstable, and/or significant and untreated medical illness (e.g., infection, unstable diabetes, uncontrolled hypertension) A clinically significant echocardiogram (ECG) abnormality in the opinion of the investigator Pregnant or breastfeeding Use of prohibited concomitant therapy History of severe allergy or hypersensitivity Dependence on alcohol or illegal drugs Use of any of the following medications during the trial: antipsychotic medications other than risperidone; psychostimulants; or antidepressants

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tropisetron<br>Tropisetron (10mg/day) + risperidone(6mg/day) | Drug: Tropisetron<br>* 10 mg/day<br>* Other names: Navoban;Drug: Risperidone<br>* 6mg/day<br>* Other names: Risperdal, Ridal, Rispolept;|
| Placebo Comparator: Placebo<br>Placebo + risperidone (6mg/day) | Drug: Placebo<br>* placebo<br>Drug: Risperidone<br>* 6mg/day<br>* Other names: Risperdal, Ridal, Rispolept;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Cognition Domains | The following 8 scales are combined into a single index that is normalized with a mean score of 100 and a standard deviation of 10. Higher scores are considered better cognitive performance. No subscales scores are reported and a final standardized score is reported as the average of the standardized scores on each of these scales. Here is the listing of component scales that were translated into Chinese and used for this study: Brief Assessment of Cognition in Schizophrenia (BACS): Symbol-Coding Trail Making Test: Part A Attention/Vigilance Continuous Performance Test-Identical Pairs (CPT-IP)* Wechsler Memory Scale®-3rd Ed. (WMS®-III): Spatial Span + Letter-Number Span Hopkins Verbal Learning Test-Revised™ (HVLT-R™) Brief Visuospatial Memory Test-Revised (BVMT-R™) Neuropsychological Assessment Battery® (NAB®): Mazes Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT™): | end of 12 wk treatment |