Smoking Cessation, Schizophrenia
Conditions
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.
Interventions
Sponsors
National Institute of Mental Health (NIMH)
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Cognition Domains | end of 12 wk treatment | 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™): |
Countries
China, United States
Participant flow
Recruitment details
The recruitment period began in May 2006 and ended in April 2011. Participants were approached for participation in this study after being hospitalized for at least 2 weeks if they were schizophrenic and capable of providing written informed consent.
Pre-assignment details
After signing informed consent for participation in the study, subjects were interviewed by study doctor and all medical and psychiatric data were reviewed prior to admitting the subject and beginning medication.
Participants by arm
| Arm | Count |
|---|---|
| Tropisetron Tropisetron (10mg/day) + risperidone(6mg/day) | 90 |
| Placebo Placebo + risperidone (6mg/day) | 89 |
| Total | 179 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 8 |
| Overall Study | Antipsychotic medication changed | 4 | 2 |
| Overall Study | Withdrawal by Subject | 10 | 10 |
Baseline characteristics
| Characteristic | Placebo | Tropisetron | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 89 Participants | 90 Participants | 179 Participants |
| Age, Continuous | 28.3 years STANDARD_DEVIATION 9.9 | 28.8 years STANDARD_DEVIATION 9.2 | 28.6 years STANDARD_DEVIATION 9.6 |
| Region of Enrollment China | 89 participants | 90 participants | 179 participants |
| Sex: Female, Male Female | 50 Participants | 52 Participants | 102 Participants |
| Sex: Female, Male Male | 39 Participants | 38 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 90 | 6 / 89 |
| serious Total, serious adverse events | 0 / 90 | 0 / 89 |
Outcome results
Primary
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™):
Time frame: end of 12 wk treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tropisetron | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Cognition Domains | 96 units on a scale | Standard Deviation 16 |
| Placebo | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Cognition Domains | 95 units on a scale | Standard Deviation 15 |
p-value: <0.05ANCOVA