SchizophreniaNCT00375050
Treatment of Refractory Schizophrenia With Riluzole
A study testing Riluzole in people with Schizophrenia and Schizoaffective, run by Yale University at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia, Schizoaffective
- What is being tested?
- Riluzole
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- May 2002to 29 Aug 2006
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women with a diagnosis of schizophrenia or schizoaffective disorder as defined by DSM- IV criteria.
- Age between 18 and 65. Special attention will be placed on selective enrolling of patients 18-25 to assess that they have been exposed to adequate medication trials (minimum two medications) for sufficient length of time.
- During the 3 months prior to study entry, the patient must not have been an inpatient in a hospital for longer than 4 weeks (cumulative hospitalizations) due to worsening of psychiatric illness (although could have been participating in an inpatient research protocol).
- Patients able to comprehend and satisfactorily comply with the protocol requirements;
- Patients with a PANSS total score of 60 or higher and a score of 4 (moderate) or higher on two or more of the following PANSS items: delusions, hallucinatory behavior, conceptual disorganization or suspiciousness.
- CGI scale rating of at least mildly ill, but not greater than severely ill.
- For women only: The patient must be non-pregnant, non-lactating, or has undergone tubal ligation, bilateral oophorectomy or hysterectomy; or the patient must be at least one year post menopausal; or the patient a) has negative urine or serum pregnancy test (Beta HCG) and b) agrees to reliably practice contraception throughout the study.
Who cannot join
- Primary psychiatric diagnosis other than schizophrenia or schizoaffective disorder.
- Patients who have had psychosurgery
- Recent (< 3 weeks) change in antipsychotic regimen
- Presence of clinically significant somatic disease that requires frequent changes in medications or that could be aggravated by taking riluzole (i.e. severe liver illness)
- Currently receiving treatment with potentially hepatotoxic drugs (e.g. allopurinol, methyldopa, sulfasalazine)
- HIV positive, as assessed by blood testing (in part to avoid subjects with possible brain HIV infection and to avoid rare complications of rarely occurring riluzole induced neutropenia)
- Patients who pose immediate or significant enough risk for suicide or harm for others as assessed by the study MD.
- Pregnant or nursing women, or women of childbearing potential who do not use adequate contraception or who are judged to be unreliable in their use of contraception (because there is not enough experience with riluzole use in nursing or pregnant women)
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale Department of Psychiatry
New Haven, Connecticut, 06519
About this study
Official title: Neuroprotective Treatment of Refractory Schizophrenia With Riluzole 01T-432
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.
Read the detailed description
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.
- Conditions
- Schizophrenia, Schizoaffective
- Being tested
- Riluzole, Placebo
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiluzoleDrug
Also called Rilutek
PlaceboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| Riluzole | Experimental | Not described Receives: Drug: Riluzole |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
PANSS (Positive and Negative Syndrome Scale)
Measured: 12 weeks
SANS (Scale for the Assessment of Negative Symptoms)
Measured: 12 weeks
CGI- Clinical Global Impression Scale
Measured: 12 weeks
Calgary Depression Scale: To assess mood symptoms in psychotic patients
Measured: 12 weeks
Neuropsychological tests:
Measured: 12 weeks
Computerized Working Memory Task
Measured: 12 weeks
Verbal Fluency
Measured: 12 weeks
HVLT-Hopkins Verbal Learning Test
Measured: 12 weeks
DSST-Digit Symbol Substitution Test
Measured: 12 weeks
Continuous performance test
Measured: 12 weeks
CANTAB- Cambridge Neuropsychological Test Automated Battery
Measured: 12 weeks
AIMS (abnormal involuntary movement scale), EPS (extrapyramidal symptom) assessment, Barnes akathisia scale, Simpson Angus scale
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2006 (estimated)
- Study startMay 2002
- Primary completion29 Aug 2006
- Study completion29 Aug 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Responsible party
- Sponsor
- Investigators
- Zoran Zimolo, MD, Ph.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00375050
- Sponsor's protocol ID
- 13175
- Status last verified
- Dec 2019
- First submitted
- 8 Sep 2006
- Last updated
- 9 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuroprotective Treatment of Refractory Schizophrenia With Riluzole 01T-432
- ClinicalTrials.gov ID
- NCT00375050
- Acronym / sponsor ID
- 13175
- Conditions
- Schizophrenia, Schizoaffective
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Study start
- May 2002
- Primary completion
- 29 Aug 2006 (actual)
- Study completion
- 29 Aug 2006 (actual)
- First posted
- 12 Sep 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Riluzole | Experimental | Drug: Riluzole |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Men or women with a diagnosis of schizophrenia or schizoaffective disorder as defined by DSM- IV criteria.
- Age between 18 and 65. Special attention will be placed on selective enrolling of patients 18-25 to assess that they have been exposed to adequate medication trials (minimum two medications) for sufficient length of time.
- During the 3 months prior to study entry, the patient must not have been an inpatient in a hospital for longer than 4 weeks (cumulative hospitalizations) due to worsening of psychiatric illness (although could have been participating in an inpatient research protocol).
- Patients able to comprehend and satisfactorily comply with the protocol requirements;
- Patients with a PANSS total score of 60 or higher and a score of 4 (moderate) or higher on two or more of the following PANSS items: delusions, hallucinatory behavior, conceptual disorganization or suspiciousness.
Key exclusion criteria (8 listed)
- Primary psychiatric diagnosis other than schizophrenia or schizoaffective disorder.
- Patients who have had psychosurgery
- Recent (< 3 weeks) change in antipsychotic regimen
- Presence of clinically significant somatic disease that requires frequent changes in medications or that could be aggravated by taking riluzole (i.e. severe liver illness)
- Currently receiving treatment with potentially hepatotoxic drugs (e.g. allopurinol, methyldopa, sulfasalazine)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RiluzoleAlso: Rilutek | Drug | Riluzole |
| Placeboplacebo | Drug | Placebo |
Primary outcome
PANSS (Positive and Negative Syndrome Scale)
Time frame: 12 weeks
SANS (Scale for the Assessment of Negative Symptoms)
Time frame: 12 weeks
CGI- Clinical Global Impression Scale
Time frame: 12 weeks
Calgary Depression Scale: To assess mood symptoms in psychotic patients
Time frame: 12 weeks
Neuropsychological tests:
Time frame: 12 weeks
Computerized Working Memory Task
Time frame: 12 weeks
Verbal Fluency
Time frame: 12 weeks
HVLT-Hopkins Verbal Learning Test
Time frame: 12 weeks
DSST-Digit Symbol Substitution Test
Time frame: 12 weeks
Continuous performance test
Time frame: 12 weeks
CANTAB- Cambridge Neuropsychological Test Automated Battery
Time frame: 12 weeks
AIMS (abnormal involuntary movement scale), EPS (extrapyramidal symptom) assessment, Barnes akathisia scale, Simpson Angus scale
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zoran Zimolo, MD, Ph.D. principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Riluzole in people with Schizophrenia and Schizoaffective, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PANSS (Positive and Negative Syndrome Scale) (time frame: 12 weeks). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2019.