Psychosis, SchizophreniaPhase 4NCT00272584
CARE Study: Improving Treatment for the Most Severely Ill With Schizophrenia
A Phase 4 study testing Risperidone in people with Psychosis, Schizophrenia, run by University of British Columbia at 1 site in Canada.
Trial summary
This is a 9 week, multicentre, randomized, double-blind, placebo-controlled trial with two parallel groups. There is also an open-label extension phase of 18 weeks. Both medications to be used in the study, clozapine and risperidone, are fully approved for the treatment of schizophrenia. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Psychosis, Schizophrenia
- What is being tested?
- Risperidone
- How many people
- 100 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2001to Jan 2004
- Phase
- Phase 4
- 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
- Subjects treated with clozapine for the indication of poor response to other antipsychotic medications.
- Treatment with clozapine is at a stable dose for at least 12 weeks. Dose must be 400 mg/day or more, unless side effects limited increase of dose.
Who cannot join
- Subjects with significant alcohol or substance abuse in the past 3 months.
- Subjects with a previous trial of risperidone augmentation of clozapine
- Subjects who are pregnant, breast-feeding, or women of child-bearing potential not using adequate contraception
- Subjects requiring treatment with anticonvulsants.
- Subjects with known hypersensitivity or allergy to risperidone.
- Subjects with hematological or other contraindications to continued clozapine treatment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: International Study of Improving Treatment for the Most Severely Ill With Schizophrenia
This is a 9 week, multicentre, randomized, double-blind, placebo-controlled trial with two parallel groups. There is also an open-label extension phase of 18 weeks. Both medications to be used in the study, clozapine and risperidone, are fully approved for the treatment of schizophrenia.
Read the detailed description
Subjects may be inpatients or outpatients. All subjects will be treated throughout the study with clozapine, at a dose of 400 mg or more, unless limited by side effects. After screening, subjects will be augmented with placebo for 7 days. Any subject with a reduction in PANSS total score of 20% or greater will be discontinued from the study. Beginning on day 8, subjects will be randomized to continued augmentation of clozapine with placebo, or to augmentation with risperidone. The initial daily dose of risperidone will be 1.0 mg, increased in 1.0 mg increments to a total of 3.0 mg/day over a two week period. Subjects unable to tolerate at least one tablet of study medication will be dropped from the study. At the end of 8 weeks following randomization, at the choice of the investigator, open-label risperidone augmentation can be started.
The primary outcome measure is the PANSS total score at week 9. Subjects will be classified as responders if the improvement in PANSS total score is 20% or greater, and the proportion of responders in each group will be determined. Complementary outcome measures will be the CGI severity score, CGI improvement score, and SOFAS score. Safety and tolerance will be assessed by reports of adverse events and clinically significant changes in vital signs, weight, waist circumference, extrapyramidal side effects, metabolic and hematological measures.
- Conditions
- Psychosis, Schizophrenia
- Being tested
- Risperidone
- Keywords
- Psychosis, schizophrenia, schizoaffective, clozapine, risperidone
- Medical subject headings
- Psychotic Disorders, Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RisperidoneDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
For 100 subjects with incomplete response to adequate treatment with clozapine, the primary objective is to determine if risperidone augmentation of clozapine is superior to augmentation with placebo, using the outcome measure of total PANSS score
Secondary outcomes (4)
Additional outcome measures will be: proportion of subjects with a 20% or greater reduction in PANSS total score, CGI severity score, CGI improvement score and SOFAS score.
To assess the safety of risperidone augmentation, severity of extrapyramidal side effects, metabolic measures, and general side effects will be studied. Hematological monitoring will be carried out.
To determine if risperidone augmentation has effects on cognition, a neuropsychological test battery will be carried out.
The predictive value of neurocognitive testing, and DNA analysis for results of risperidone augmentation will be studied.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2006 (estimated)
- Study startJun 2001
- Study completionJan 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Psychosis, SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 100 participants
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Investigators
- William Honer, MD, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00272584
- Sponsor's protocol ID
- C0-0280
- Status last verified
- Jan 2006
- First submitted
- 3 Jan 2006
- Last updated
- 8 May 2006
- Results posted
- No
Publications
Honer WG, Thornton AE, Chen EY, Chan RC, Wong JO, Bergmann A, Falkai P, Pomarol-Clotet E, McKenna PJ, Stip E, Williams R, MacEwan GW, Wasan K, Procyshyn R; Clozapine and Risperidone Enhancement (CARE) Study Group. Clozapine alone versus clozapine and risperidone with refractory schizophrenia. N Engl J Med. 2006 Feb 2;354(5):472-82. doi: 10.1056/NEJMoa053222.
PubMed 16452559Thornton AE, Procyshyn RM, Barr AM, MacEwan GW, Honer WG. Cognition and Plasma Ratio of Clozapine to N-desmethylclozapine in Patients With Clozapine-Resistant Schizophrenia. Am J Psychiatry. 2015 Dec;172(12):1259. doi: 10.1176/appi.ajp.2015.15070899. No abstract available.
PubMed 26619773
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International Study of Improving Treatment for the Most Severely Ill With Schizophrenia
- ClinicalTrials.gov ID
- NCT00272584
- Acronym / sponsor ID
- C0-0280
- Conditions
- Psychosis, Schizophrenia
- Keywords
- Psychosis, schizophrenia, schizoaffective, clozapine, risperidone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- Jun 2001
- Study completion
- Jan 2004
- First posted
- 6 Jan 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.
This is a 9 week, multicentre, randomized, double-blind, placebo-controlled trial with two parallel groups. There is also an open-label extension phase of 18 weeks. Both medications to be used in the study, clozapine and risperidone, are fully approved for the treatment of schizophrenia.
Detailed description
Subjects may be inpatients or outpatients. All subjects will be treated throughout the study with clozapine, at a dose of 400 mg or more, unless limited by side effects. After screening, subjects will be augmented with placebo for 7 days. Any subject with a reduction in PANSS total score of 20% or greater will be discontinued from the study. Beginning on day 8, subjects will be randomized to continued augmentation of clozapine with placebo, or to augmentation with risperidone. The initial daily dose of risperidone will be 1.0 mg, increased in 1.0 mg increments to a total of 3.0 mg/day over a two week period. Subjects unable to tolerate at least one tablet of study medication will be dropped from the study. At the end of 8 weeks following randomization, at the choice of the investigator, open-label risperidone augmentation can be started.
The primary outcome measure is the PANSS total score at week 9. Subjects will be classified as responders if the improvement in PANSS total score is 20% or greater, and the proportion of responders in each group will be determined. Complementary outcome measures will be the CGI severity score, CGI improvement score, and SOFAS score. Safety and tolerance will be assessed by reports of adverse events and clinically significant changes in vital signs, weight, waist circumference, extrapyramidal side effects, metabolic and hematological measures.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Subjects treated with clozapine for the indication of poor response to other antipsychotic medications.
- Treatment with clozapine is at a stable dose for at least 12 weeks. Dose must be 400 mg/day or more, unless side effects limited increase of dose.
Key exclusion criteria (6 listed)
- Subjects with significant alcohol or substance abuse in the past 3 months.
- Subjects with a previous trial of risperidone augmentation of clozapine
- Subjects who are pregnant, breast-feeding, or women of child-bearing potential not using adequate contraception
- Subjects requiring treatment with anticonvulsants.
- Subjects with known hypersensitivity or allergy to risperidone.
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 |
|---|---|---|
| Risperidone | Drug | – |
Primary outcome
For 100 subjects with incomplete response to adequate treatment with clozapine, the primary objective is to determine if risperidone augmentation of clozapine is superior to augmentation with placebo, using the outcome measure of total PANSS score
4 secondary outcomes
Additional outcome measures will be: proportion of subjects with a 20% or greater reduction in PANSS total score, CGI severity score, CGI improvement score and SOFAS score.
To assess the safety of risperidone augmentation, severity of extrapyramidal side effects, metabolic measures, and general side effects will be studied. Hematological monitoring will be carried out.
To determine if risperidone augmentation has effects on cognition, a neuropsychological test battery will be carried out.
The predictive value of neurocognitive testing, and DNA analysis for results of risperidone augmentation will be studied.
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 8 May 2006.
- Results publication: PubMed 16452559Honer WG, Thornton AE, Chen EY, Chan RC, Wong JO, Bergmann A, Falkai P, Pomarol-Clotet E, McKenna PJ, Stip E, Williams R, MacEwan GW, Wasan K, Procyshyn R; Clozapine and Risperidone Enhancement (CARE) Study Group. Clozapine alone versus clozapine and risperidone with refractory schizophrenia. N Engl J Med. 2006 Feb 2;354(5):472-82. doi: 10.1056/NEJMoa053222.
- Derived from this study: PubMed 26619773Thornton AE, Procyshyn RM, Barr AM, MacEwan GW, Honer WG. Cognition and Plasma Ratio of Clozapine to N-desmethylclozapine in Patients With Clozapine-Resistant Schizophrenia. Am J Psychiatry. 2015 Dec;172(12):1259. doi: 10.1176/appi.ajp.2015.15070899. No abstract available.
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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.
William Honer, MD principal investigator
University of British Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Risperidone in people with Psychosis, Schizophrenia, run by University of British Columbia at 1 site in Canada.
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 2 inclusion and 6 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 8 May 2006. 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 Canada. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
For 100 subjects with incomplete response to adequate treatment with clozapine, the primary objective is to determine if risperidone augmentation of clozapine is superior to augmentation with placebo, using the outcome measure of total PANSS score. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00272584, which also lists 2 linked publications.
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 8 May 2006.