Effectiveness of Tropisetron Plus Risperidone for Improving Cognitive and Perceptual Disturbances in Schizophrenia
Study Details
Study Description
Brief Summary
This study will determine the effectiveness of tropisetron plus risperidone in improving cognitive symptoms in Chinese people with schizophrenia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Tropisetron Tropisetron (10mg/day) + risperidone(6mg/day) |
Drug: Tropisetron
10 mg/day
Other Names:
Drug: Risperidone
6mg/day
Other Names:
|
| Placebo Comparator: Placebo Placebo + risperidone (6mg/day) |
Drug: Placebo
placebo
Drug: Risperidone
6mg/day
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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™):
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Baylor College of Medicine - Michael E. DeBakey VA Medical Center | Houston | Texas | United States | 77030 |
| 2 | Beijing Hui-Long Guan Hospital | Beijing | China |
Sponsors and Collaborators
- Baylor College of Medicine
- National Institute of Mental Health (NIMH)
Investigators
- Principal Investigator: Thomas Kosten, MD, Baylor College of Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- U01MH079639
- U01MH079639
Study Results
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 Detail | 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. |
| Arm/Group Title | Tropisetron | Placebo |
|---|---|---|
| Arm/Group Description | Tropisetron (10mg/day) + risperidone(6mg/day) | Placebo + risperidone (6mg/day) |
| Period Title: Overall Study | ||
| STARTED | 90 | 89 |
| COMPLETED | 68 | 69 |
| NOT COMPLETED | 22 | 20 |
Baseline Characteristics
| Arm/Group Title | Tropisetron | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Tropisetron (10mg/day) + risperidone(6mg/day) | Placebo + risperidone (6mg/day) | Total of all reporting groups |
| Overall Participants | 90 | 89 | 179 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
90
100%
|
89
100%
|
179
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
28.8
(9.2)
|
28.3
(9.9)
|
28.6
(9.6)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
52
57.8%
|
50
56.2%
|
102
57%
|
| Male |
38
42.2%
|
39
43.8%
|
77
43%
|
| Region of Enrollment (participants) [Number] | |||
| China |
90
100%
|
89
100%
|
179
100%
|
Outcome Measures
| Title | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Cognition Domains |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tropisetron | Placebo |
|---|---|---|
| Arm/Group Description | Tropisetron (10mg/day) + risperidone(6mg/day) | Placebo + risperidone (6mg/day) |
| Measure Participants | 90 | 89 |
| Mean (Standard Deviation) [units on a scale] |
96
(16)
|
95
(15)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tropisetron, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Adverse Events
| Time Frame | 6 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Tropisetron | Placebo | ||
| Arm/Group Description | Tropisetron (10mg/day) + risperidone(6mg/day) | Placebo + risperidone (6mg/day) | ||
All Cause Mortality |
||||
| Tropisetron | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Tropisetron | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/90 (0%) | 0/89 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Tropisetron | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/90 (8.9%) | 6/89 (6.7%) | ||
| General disorders | ||||
| Other Adverse Event | 8/90 (8.9%) | 8 | 6/89 (6.7%) | 6 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Thomas R. Kosten |
|---|---|
| Organization | Baylor College of Medicine |
| Phone | (713) 794-7032 |
| kosten@bcm.edu |
- U01MH079639
- U01MH079639