Treatment of Refractory Schizophrenia With Riluzole
Recruitment status was Recruiting
|First Received Date ICMJE||September 8, 2006|
|Last Updated Date||September 8, 2006|
|Start Date ICMJE||May 2002|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Treatment of Refractory Schizophrenia With Riluzole|
|Official Title ICMJE||Neuroprotective Treatment of Refractory Schizophrenia With Riluzole|
The proposed study would evaluate the benefits of riluzole add-on treatment to patients with schizophrenia who are already receiving medications, but still experience symptoms. Neuroprotective medication riluzole is currently approved for treatment of amyotrophic lateral sclerosis (Lou Gehrig's disease), a severe neurological illness. Due to its unique mechanism of action, riluzole, if effective in helping the symptoms of schizophrenia, would open novel directions in treatment of schizophrenia.
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.
|Study Type ICMJE||Interventional|
|Study Phase||Not Provided|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Riluzole|
|Study Arm (s)||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Completion Date||October 2006|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 65 Years|
|Accepts Healthy Volunteers||No|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00375050|
|Other Study ID Numbers ICMJE||01T-432|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Yale University|
|Collaborators ICMJE||Stanley Medical Research Institute|
|Information Provided By||Yale University|
|Verification Date||September 2006|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP