SchizophreniaPhase 4AMICUSNCT01246232
Amisulpride Augmentation in Clozapine-unresponsive Schizophrenia
A Phase 4 study testing Amisulpride in people with Schizophrenia, run by Imperial College London at 3 sites in United Kingdom.
Trial summary
Schizophrenia is a mental health problem usually starting in the late teens/early twenties, and often lasting many years. The standard medication ('antipsychotics') for this problem is usually helpful, and if taken continually can keep people well, reducing the likelihood of further episodes. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Amisulpride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Sep 2011to Mar 2015
- 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
- A criterion level of persistent symptom severity despite an adequate trial of clozapine monotherapy in terms of dosage, duration and adherence (as used by Honer et al 2006):
- Treatment for at least 12 weeks at a stable dose of 400 mg or more of clozapine a day, unless the size of the dose was limited by side effects
- A total score of 80 or greater at baseline on the Positive and Negative Syndrome Scale (PANSS: Kay et al 1987, 1988); the range of possible scores is 30 to 210, with higher scores indicating more severe symptoms.
- A Clinical Global Impressions (CGI: Guy 1976) score of 4 or greater (range of possible scores, 1=not mentally ill to 7=extremely ill)
- A Social and Occupational Functioning Assessment Scale (SOFAS: Goldman et al 1992, DSM-IV 1994) score of 40 or less; range of possible scores, 1 to 100, with lower scores indicating impaired functioning.
- Age 18-65 years, inclusive
- Clinically stable for the last 3 months with a consistent clozapine regimen.
- Competent and willing to provide written, informed consent.
Who cannot join
- Clinically-significant alcohol/substance use in the previous three months
- Developmental disability
- Indication for current treatment with clozapine was intolerance/movement disorder
- A previous trial of clozapine augmentation with amisulpride.
- Existing relevant physical health problems: such as cardiovascular disease, previous problems with prolactin, and impaired liver/ renal function.
- Any woman who is pregnant or planning a pregnancy, and any woman of child bearing potential unless using adequate contraception.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
University College London
London, NW3 2PF
Imperial College London
London, W6 8LN
University of Manchester
Manchester, M13 9WL
About this study
Schizophrenia is a mental health problem usually starting in the late teens/early twenties, and often lasting many years. The standard medication ('antipsychotics') for this problem is usually helpful, and if taken continually can keep people well, reducing the likelihood of further episodes. However, in up to one in three people with schizophrenia, the illness does not show much improvement with antipsychotic medication. For some of these 'resistant' illnesses, one particular antipsychotic, clozapine, can work well, but one disadvantage is the risk of a severe blood side effect which means that regular blood testing is necessary. If the response to clozapine treatment is disappointing, there is some evidence that adding another antipsychotic can sometimes produce more improvement. However, it seems that the added antipsychotic may need to be taken by the person for at least 10 weeks in order to work well. The investigators plan to test carefully the possible benefits and problems when the antipsychotic amisulpride or a dummy tablet ('placebo') is added to clozapine for 12 weeks in people whose schizophrenia illness has not been helped much by any antipsychotic medication on its own, and who are now taking clozapine, but again with not much improvement. The investigators have chosen amisulpride because its pharmacological action may be complementary to that of clozapine, and also it is less likely than some other antipsychotics to compound some of the characteristic side effects of clozapine, such as sedation, weight gain and other metabolic problems.
Adjunctive amisulpride or placebo will be randomly assigned. The investigators expect that adding amisulpride will be more likely to cause an improvement than adding placebo. But the investigators should learn more about the risks and side effects of combining these two medications. Also, the investigators should gain a greater understanding of the possible benefits of adding another antipsychotic to clozapine in relation to particular problem symptoms, and a person's ability to live and work in the community.
Read the detailed description
This 12-week, placebo-controlled RCT will be conducted in secondary care, specifically mental health services, at UK centres. The health technology to be assessed is the augmentation of clozapine treatment with another second-generation antipsychotic, amisulpride, which will be compared with placebo: 400mg amisulpride or 1 matching placebo capsule for the first 4 weeks, then the option of titrating up to 800mg amisulpride or 2 matching placebo capsules for the remaining 8 weeks. The study will be double-blind, with medication supplied as identical capsules containing either 400mg amisulpride or placebo. The optimum dose of clozapine at entry and subsequent augmentation will be achieved through a flexible dosing regimen whereby treating psychiatrists will be able to flexibly alter dose regimens to maximise clinical risk-benefit ratios; there will be opportunities for clinical titration of clozapine dose at two and six weeks. Any direct pharmacokinetic effect on clozapine levels will be assessed by pre- and post-augmentation plasma levels of clozapine, samples being taken at baseline and at the end of the 12 weeks. Recommended pharmacovigilance procedures will be followed. Clinicians will be asked not to prescribe any additional medication during the course of the study, and will be reminded of the drugs with potential adverse interactions, as mentioned in the SPCs for clozapine and amisulpride. Medication adherence will be assessed by 'pill count' and clozapine/norclozapine plasma level ratio.
Therapeutic improvement will be assessed in terms of overall symptom severity, but also using broader, clinically-relevant outcome measures of social and occupational function and target symptoms and/or behaviours as well as overall health status and utility. Side effects will be systematically assessed. The costs and outcomes for a cost effectiveness acceptability and net benefit analysis will also be measured. The primary economic measure will be the incremental cost effectiveness ratio of clozapine augmentation, estimated as the net cost of clozapine augmentation divided by net QALY of clozapine augmentation.
Twenty-four months will be allowed for recruitment of participants, plus 3 months for the final follow-up assessments.
- Conditions
- Schizophrenia
- Being tested
- Amisulpride, placebo
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmisulprideDrug
Clozapine augmentation with another second-generation antipsychotic, amisulpride (400mg amisulpride for the first 4 weeks, then the option of titrating up to 800mg amisulpride for the remaining 8 weeks).
placeboDrug
Clozapine augmentation with 1 capsule placebo for the first 4 weeks, then the option of titrating up to 2 capsules placebo for the remaining 8 weeks).
| Study group | Role | What they receive |
|---|---|---|
| Amisulpride | Experimental | 400mg, 2 x 200mg amisulpride capsules for the first 4 weeks, then the option of titrating up to 800mg, 4 x 200mg amisulpride capsules for the remaining 8 weeks. Receives: Drug: Amisulpride |
| Placebo | Placebo comparator | 400mg, 2 x 200mg amisulpride capsules, or 2 matching placebo capsules for the first 4 weeks, then the option of titrating up to 800mg, 4 x 200mg amisulpride capsules, or 4 matching placebo capsules for the remaining 8 weeks. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total score on the Positive and Negative Syndrome Scale
Measured: Baseline, and 6 and 12 weeks
Secondary outcomes (5)
Social and Occupational Functioning Assessment Scale
Measured: Baseline, and 6 and 12 weeks
Calgary Depression Rating Scale for Schizophrenia
Measured: Baseline, and 6 and 12 weeks
Schedule for the Assessment of Insight
Measured: Baseline, and 6 and 12 weeks
Service Engagement Scale
Measured: Baseline, and 6 and 12 weeks
Antipsychotic Non-Neurological Side Effects Scale
Measured: Baseline, and 6 and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2010 (estimated)
- Study startSep 2011
- Primary completionMar 2015
- Study completionMar 2015
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 Imperial College LondonThe 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- University of Manchester, University College, London
- Responsible party
- Sponsor
- Investigators
- Thomas R Barnes, MD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01246232
- Sponsor's protocol ID
- CRO1498
- Other IDs
- HTA 08/116/12, 2010-018963-40
- Acronym
- AMICUS
- Status last verified
- Sep 2011
- First submitted
- 22 Nov 2010
- Last updated
- 1 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Amisulpride Augmentation in Clozapine-unresponsive Schizophrenia
- ClinicalTrials.gov ID
- NCT01246232
- Acronym / sponsor ID
- AMICUS / CRO1498
- Conditions
- Schizophrenia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- University of Manchester, University College, London
- Study start
- Sep 2011
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 23 Nov 2010 (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.
Schizophrenia is a mental health problem usually starting in the late teens/early twenties, and often lasting many years. The standard medication ('antipsychotics') for this problem is usually helpful, and if taken continually can keep people well, reducing the likelihood of further episodes. However, in up to one in three people with schizophrenia, the illness does not show much improvement with antipsychotic medication. For some of these 'resistant' illnesses, one particular antipsychotic, clozapine, can work well, but one disadvantage is the risk of a severe blood side effect which means that regular blood testing is necessary. If the response to clozapine treatment is disappointing, there is some evidence that adding another antipsychotic can sometimes produce more improvement. However, it seems that the added antipsychotic may need to be taken by the person for at least 10 weeks in order to work well. The investigators plan to test carefully the possible benefits and problems when the antipsychotic amisulpride or a dummy tablet ('placebo') is added to clozapine for 12 weeks in people whose schizophrenia illness has not been helped much by any antipsychotic medication on its own, and who are now taking clozapine, but again with not much improvement. The investigators have chosen amisulpride because its pharmacological action may be complementary to that of clozapine, and also it is less likely than some other antipsychotics to compound some of the characteristic side effects of clozapine, such as sedation, weight gain and other metabolic problems.
Adjunctive amisulpride or placebo will be randomly assigned. The investigators expect that adding amisulpride will be more likely to cause an improvement than adding placebo. But the investigators should learn more about the risks and side effects of combining these two medications. Also, the investigators should gain a greater understanding of the possible benefits of adding another antipsychotic to clozapine in relation to particular problem symptoms, and a person's ability to live and work in the community.
Detailed description
This 12-week, placebo-controlled RCT will be conducted in secondary care, specifically mental health services, at UK centres. The health technology to be assessed is the augmentation of clozapine treatment with another second-generation antipsychotic, amisulpride, which will be compared with placebo: 400mg amisulpride or 1 matching placebo capsule for the first 4 weeks, then the option of titrating up to 800mg amisulpride or 2 matching placebo capsules for the remaining 8 weeks. The study will be double-blind, with medication supplied as identical capsules containing either 400mg amisulpride or placebo. The optimum dose of clozapine at entry and subsequent augmentation will be achieved through a flexible dosing regimen whereby treating psychiatrists will be able to flexibly alter dose regimens to maximise clinical risk-benefit ratios; there will be opportunities for clinical titration of clozapine dose at two and six weeks. Any direct pharmacokinetic effect on clozapine levels will be assessed by pre- and post-augmentation plasma levels of clozapine, samples being taken at baseline and at the end of the 12 weeks. Recommended pharmacovigilance procedures will be followed. Clinicians will be asked not to prescribe any additional medication during the course of the study, and will be reminded of the drugs with potential adverse interactions, as mentioned in the SPCs for clozapine and amisulpride. Medication adherence will be assessed by 'pill count' and clozapine/norclozapine plasma level ratio.
Therapeutic improvement will be assessed in terms of overall symptom severity, but also using broader, clinically-relevant outcome measures of social and occupational function and target symptoms and/or behaviours as well as overall health status and utility. Side effects will be systematically assessed. The costs and outcomes for a cost effectiveness acceptability and net benefit analysis will also be measured. The primary economic measure will be the incremental cost effectiveness ratio of clozapine augmentation, estimated as the net cost of clozapine augmentation divided by net QALY of clozapine augmentation.
Twenty-four months will be allowed for recruitment of participants, plus 3 months for the final follow-up assessments.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Amisulpride | Experimental | Drug: Amisulpride400mg, 2 x 200mg amisulpride capsules for the first 4 weeks, then the option of titrating up to 800mg, 4 x 200mg amisulpride capsules for the remaining 8 weeks. |
| Placebo | Placebo comparator | Drug: placebo400mg, 2 x 200mg amisulpride capsules, or 2 matching placebo capsules for the first 4 weeks, then the option of titrating up to 800mg, 4 x 200mg amisulpride capsules, or 4 matching placebo capsules for the remaining 8 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- A criterion level of persistent symptom severity despite an adequate trial of clozapine monotherapy in terms of dosage, duration and adherence (as used by Honer et al 2006):
- Age 18-65 years, inclusive
- Clinically stable for the last 3 months with a consistent clozapine regimen.
- Competent and willing to provide written, informed consent.
Key exclusion criteria (6 listed)
- Clinically-significant alcohol/substance use in the previous three months
- Developmental disability
- Indication for current treatment with clozapine was intolerance/movement disorder
- A previous trial of clozapine augmentation with amisulpride.
- Existing relevant physical health problems: such as cardiovascular disease, previous problems with prolactin, and impaired liver/ renal function.
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 |
|---|---|---|
| AmisulprideClozapine augmentation with another second-generation antipsychotic, amisulpride (400mg amisulpride for the first 4 weeks, then the option of titrating up to 800mg amisulpride for the remaining 8 weeks). | Drug | Amisulpride |
| placeboClozapine augmentation with 1 capsule placebo for the first 4 weeks, then the option of titrating up to 2 capsules placebo for the remaining 8 weeks). | Drug | Placebo |
Primary outcome
Total score on the Positive and Negative Syndrome Scale
Time frame: Baseline, and 6 and 12 weeks
5 secondary outcomes
Social and Occupational Functioning Assessment Scale
Time frame: Baseline, and 6 and 12 weeks
Calgary Depression Rating Scale for Schizophrenia
Time frame: Baseline, and 6 and 12 weeks
Schedule for the Assessment of Insight
Time frame: Baseline, and 6 and 12 weeks
Service Engagement Scale
Time frame: Baseline, and 6 and 12 weeks
Antipsychotic Non-Neurological Side Effects Scale
Time frame: Baseline, and 6 and 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 1 Apr 2015.
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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.
Thomas R Barnes, MD principal investigator
Imperial College London
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Amisulpride in people with Schizophrenia, run by Imperial College London at 3 sites in United Kingdom.
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 8 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 1 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. 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.
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?
Total score on the Positive and Negative Syndrome Scale (time frame: Baseline, and 6 and 12 weeks). 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 1 Apr 2015.