Official Title: “Tropisetron With Risperidone for Schizophrenia”

This study will determine the effectiveness of tropisetron plus risperidone in improving cognitive and perceptual disturbances and symptoms in Chinese people with schizophrenia.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Pharmacodynamics Study

Study Primary Completion Date: December 2009

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 will include assessments of cognitive functioning and treatment safety and effectiveness. Participants will also report the number of cigarettes they smoke per day and provide blood and urine samples to monitor medication levels and adherence.

Intervention(s) in this Clinical Trial

• Drug: Tropisetron
  • 10 mg/day
• Drug: Placebo
  • placebo
• Drug: Risperidone
  • 6mg/day

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Tropisetron
• Placebo Comparator: 2

Primary Measures

• Cognitive deficits as assessed by tests measuring the MATRICS cognition domains
  • Time Frame: Baseline, end of 12 wk treatment
    Safety Issue?: No

Secondary Measures

• Negative schizophrenic symptoms
  • Time Frame: Screening, baseline, every 2 weeks after for duration of study
    Safety Issue?: No
• Reduction in side effects of risperidone
  • Time Frame: baseline, every two weeks for study duration
    Safety Issue?: Yes
• Abnormality in P50 inhibition
  • Time Frame: baseline, week 12
    Safety Issue?: No
• Nicotine use among all participants who smoke
  • Time Frame: baseline, week 12
    Safety Issue?: 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:

• 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 64 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Mental Health (NIMH)

Overall Clinical Trial Officials and Contacts

Thomas Kosten, MD Principal Investigator Baylor College of Medicine  

Overall Contact: Thomas Kosten, MD 713-794-7032 kosten@bcm.edu

Information obtained from ClinicalTrials.gov on January 08, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00435370

Study ID Number: U01 MH79639

ClinicalTrials.gov Identifier: NCT00435370

Health Authority: United States: Federal Government