Treatment of Refractory Schizophrenia With Riluzole
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
|Official Title:||Neuroprotective Treatment of Refractory Schizophrenia With Riluzole|
- PANSS (Positive and Negative Syndrome Scale) [ Designated as safety issue: No ]
- SANS (Scale for the Assessment of Negative Symptoms) [ Designated as safety issue: No ]
- CGI- Clinical Global Impression Scale [ Designated as safety issue: No ]
- Calgary Depression Scale: To assess mood symptoms in psychotic patients [ Designated as safety issue: No ]
- Neuropsychological tests: [ Designated as safety issue: No ]
- Computerized Working Memory Task [ Designated as safety issue: No ]
- Verbal Fluency [ Designated as safety issue: No ]
- HVLT-Hopkins Verbal Learning Test [ Designated as safety issue: No ]
- DSST-Digit Symbol Substitution Test [ Designated as safety issue: No ]
- Continuous performance test [ Designated as safety issue: No ]
- CANTAB- Cambridge Neuropsychological Test Automated Battery [ Designated as safety issue: No ]
- AIMS (abnormal involuntary movement scale), EPS (extrapyramidal symptom) assessment, Barnes akathisia scale, Simpson Angus scale [ Designated as safety issue: No ]
|Study Start Date:||May 2002|
|Estimated Study Completion Date:||September 2016|
|Estimated Primary Completion Date:||September 2016 (Final data collection date for primary outcome measure)|
Other Name: Rilutek
|Placebo Comparator: Placebo||
Schizophrenia is perhaps one of the most debilitating illnesses. Over the past years there has been limited improvement in the efficacy of the medications used to treat this disorder. In particular, the currently available antipsychotic drugs have small efficacy against negative symptoms and cognitive impairment associated with schizophrenia. This is critical considering that both negative symptoms and cognitive deficits contribute significantly to social and vocational impairment in schizophrenic patients. Furthermore, current treatment can not always provide satisfactory control of positive symptoms. While various extracellular neurotransmitter systems (dopamine, 5HT, GABA, etc. ) have been explored as targets for antipsychotic treatment, a substantial body of evidence suggests that neurodegenerative intracellular processes might be responsible for some of the symptoms of schizophrenia, resulting in cytopathic effects or inadequate cellular functioning. Some of these processes may be triggered by excitotoxic influence of neurotransmitters (i.e. glutamate). As many neuroleptic agents currently in use have some neuroprotective properties it is possible to speculate that medications with primarily neuroprotective mode of action might be of additional help in treatment of schizophrenia.
Huntington's disease patients who in its advanced form exhibit some symptoms similar to that of psychotic illness, have, in a recent small (n=9) open label study with a neuroprotective drug riluzole, shown a temporary improvement in not only motor function, but also cognitive, and behavioral functioning (Seppi 2001).
Based on all of the above, it seems possible to expect improvement in symptoms of schizophrenia with neuroprotective agents such as riluzole.
Riluzole is the only effective medication approved for use in ALS (amyotrophic lateral sclerosis, Lou Gehrig's disease) which is one of the most severe and rapidly progressing neurodegenerative illnesses that affects motor neurons in the brain and spinal cord. A subset of ALS is inherited and involves more than 70 different mutations in the antioxidant enzyme superoxide dismutase (SOD) thereby contributing to reduced antioxidative defense against oxidative injury. This results in increased reactive oxygen species level in several organs/tissues while the bulk of symptomatology is related to degeneration in the subset of CNS neurons. Although riluzole is effective in both humans and the transgenic mouse model of familial ALS where it slows decrease in motor power, its exact neuroprotective mechanism of action is not known. Various studies suggest that riluzole might exert some of its beneficial effect by inhibition of glutamate release, inhibition of voltage-gated Na+ channels, but also intracellularly by inhibiting of protein kinase C (PKC), enzyme that was linked to oxidative neuronal injury. Although riluzole is generally well tolerated, side effects can occur and are mostly related to gastrointestinal problems, hepatotoxicity and asthenia.
This 14 week study would evaluate the benefits of riluzole add-on treatment to patients with schizophrenia on neuroleptics with refractory symptoms.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00375050
|United States, Connecticut|
|Yale Department of Psychiatry|
|New Haven, Connecticut, United States, 06519|
|Principal Investigator:||Zoran Zimolo, MD, Ph.D.||Yale University|