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

Tropisetron With Risperidone for Schizophrenia

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

Study Overview

• Status: Completed
• Conditions: Smoking Cessation; Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: Tropisetron; Drug: Risperidone

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 Type: Interventional
• Enrollment (Actual): 179
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Hui-Long Guan Hospital
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Michael E. DeBakey VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tropisetron; Tropisetron (10mg/day) + risperidone(6mg/day)	Drug: Tropisetron; 10 mg/day; Other Names: Navoban; Drug: Risperidone; 6mg/day; Other Names: Risperdal, Ridal, Rispolept
Placebo Comparator: Placebo; Placebo + risperidone (6mg/day)	Drug: Placebo; placebo; Drug: Risperidone; 6mg/day; 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

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Thomas Kosten, MD, Baylor College of Medicine

Publications and helpful links

General Publications

• Zhang XY, Liu L, Liu S, Hong X, Chen DC, Xiu MH, Yang FD, Zhang Z, Zhang X, Kosten TA, Kosten TR. Short-term tropisetron treatment and cognitive and P50 auditory gating deficits in schizophrenia. Am J Psychiatry. 2012 Sep;169(9):974-81. doi: 10.1176/appi.ajp.2012.11081289.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: February 13, 2007
• First Submitted That Met QC Criteria: February 13, 2007
• First Posted (Estimate): February 14, 2007

Study Record Updates

• Last Update Posted (Actual): March 15, 2017
• Last Update Submitted That Met QC Criteria: February 4, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Serotonin 5-HT3 Receptor Antagonists; Risperidone; Tropisetron
• Other Study ID Numbers: U01MH079639 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO