Bipolar DisorderPhase 4NCT02562287
Clozapine Versus Other Atypical Antipsychotics for Bipolar Disorder
A Phase 4 study testing Clozapine, Risperidone and Olanzapine in people with Bipolar Disorder, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
Trial summary
The clinical use of clozapine has been an unequivocal advance in the treatment of schizophrenia, a chronic and severe mental illness. A wealth of clinical data demonstrates it offers enhanced efficacy on both positive and negative symptomatology, improving cognition, functioning and quality of life. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Clozapine, Risperidone and Olanzapine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteBrazil
- Study dates
- Oct 2015to Dec 2020
- 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
- DSM-IV Bipolar I Disorder;
- having had a mood episode within the preceding year; DSM-IV rapid cyclers will be permitted to participate in this study;
- males or females between 18 and 65 years of age;
- ongoing illness symptoms including significant functional impairment;
- documented history of treatment resistance, defined as persistent symptoms despite simultaneous, adequate treatment with at least two medications: one mood stabilizer (lithium or valproate) + antipsychotic OR two mood stabilizers (at least one of them being lithium or valproate).
- each patient must have a level of understanding sufficient to agree to all the tests required by the protocol and must sign an informed consent document
Who cannot join
- patients with onset of illness after age 40 or illness resulting from secondary causes
- women who are pregnant or breastfeeding, or not using adequate contraception
- unstable medical illnesses
- clinically significant abnormal laboratory tests
- current active alcohol or substance abuse
- severe personality disorders
- contraindication to the use of clozapine or previous treatment with clozapine
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90540001
PEDRO V MAGALHAES, M.D., Ph.D.
About this study
Official title: A Randomized Controlled Trial to Evaluate the Effectiveness of Clozapine Versus Olanzapine, Quetiapine or Risperidone in Treatment Resistant Bipolar Disorder
The clinical use of clozapine has been an unequivocal advance in the treatment of schizophrenia, a chronic and severe mental illness. A wealth of clinical data demonstrates it offers enhanced efficacy on both positive and negative symptomatology, improving cognition, functioning and quality of life. It is also associated with improved compliance and a continued efficacy in long-term treatment that can be translated into a reduction of suicidality and all-cause mortality. Because of preclinical evidence that it modulates neuroplasticity and prefrontal cortex connectivity, clozapine may be an interesting strategy for further severe psychotic illnesses. Nevertheless, even considering the growing use of other atypical antipsychotics in the management of bipolar disorder, a role for clozapine has been poorly defined. The clinical evidence-base for its use in this condition is largely based on uncontrolled naturalistic trials and retrospective studies and chart reviews. Several of these have supported clozapine's efficacy in treatment-resistant bipolar disorder. Possibly because of clozapine's profile of adverse effects and lack of interest from pharmaceutical companies, only two randomized trials have examined its effectiveness. Both suggest clinically relevant antimanic and mood-stabilizing properties. Therefore, the primary objective of this trial is to determine the effectiveness of clozapine for treatment-resistant bipolar disorder. Secondary objectives include examining the effects of treatment with clozapine on cognition and functioning of patients with bipolar disorder. Tolerability and safety of long-term clozapine use will also be examined. To that end, the investigators will conduct a clinical trial with 54 patients with a history of treatment resistance. Patients will be randomized to either open-label treatment with clozapine, in combination with lithium or valproate, or open-label treatment with an atypical antipsychotic with consistent evidence of efficacy in the treatment of bipolar disorder (olanzapine, quetiapine or risperidone), also in combination with lithium or valproate. Patients will be followed for one-year and time to all-cause treatment failure will be the primary outcome measure. It is the belief of the investigators that this study will generate meaningful clinical data of tremendous importance to validate clozapine as a legitimate treatment option for treatment-resistant bipolar disorder.
- Conditions
- Bipolar Disorder
- Being tested
- Clozapine, Risperidone, Olanzapine, Quetiapine
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClozapineDrug
Also called Clozaril
Flexible dosage, with up-titration according to standard schedules employed for schezophrenia
RisperidoneDrug
Also called Risperdal
Risperidone, in a flexible dosage
OlanzapineDrug
Also called Zyprexa
Olanzapine, flexible dosage
QuetiapineDrug
Also called Seroquel
Quetiapine, flexible dosage
| Study group | Role | What they receive |
|---|---|---|
| Clozapine | Experimental | Clozapine, P.O., flexible dose, for up to 6 months Receives: Drug: Clozapine |
| Risperidone, olanzapine or quetiapine | Active comparator | Risperidone, olanzapine or quetiapine, according to clinical indication, flexible dose, for up to 6 months Receives: Drug: Risperidone; Drug: Olanzapine; Drug: Quetiapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functioning according to Functioning Assessment Short-Test
Global functioning according to Functioning Assessment Short-Test
Measured: 6 month follow up
Secondary outcomes (1)
Time to all-cause treatment failure
Include drug treatment (commencement of a new drug, restarting of a discontinued drug, or increasing the investigational drug dose in response to an emergent mood episode), admission to hospital or withdrawal from study treatment.
Measured: Six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2015 (estimated)
- Study startOct 2015
- Primary completionJun 2019 (estimated)
- Study completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by Hospital de Clinicas de Porto AlegreThe 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
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital de Clinicas de Porto Alegre
- Sponsor type
- University, hospital or other
- Collaborators
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior., Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Responsible party
- Principal investigator, Pedro Vieira da Silva Magalhães, Hospital de Clinicas de Porto Alegre
- Investigators
- PEDRO V MAGALHAES, M.D., Ph.D., Principal investigator, Hospital de Clínicas de Porto Alegre / Universidade Federal do Rio Grande do Sul
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02562287
- Sponsor's protocol ID
- 32356214200005327
- Status last verified
- Oct 2018
- First submitted
- 11 Aug 2015
- Last updated
- 2 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial to Evaluate the Effectiveness of Clozapine Versus Olanzapine, Quetiapine or Risperidone in Treatment Resistant Bipolar Disorder
- ClinicalTrials.gov ID
- NCT02562287
- Acronym / sponsor ID
- 32356214200005327
- Conditions
- Bipolar Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Hospital de Clinicas de Porto AlegreUniversity, hospital or other
- Collaborators
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior., Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Study start
- Oct 2015
- Primary completion
- Jun 2019 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 29 Sep 2015 (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 clinical use of clozapine has been an unequivocal advance in the treatment of schizophrenia, a chronic and severe mental illness. A wealth of clinical data demonstrates it offers enhanced efficacy on both positive and negative symptomatology, improving cognition, functioning and quality of life. It is also associated with improved compliance and a continued efficacy in long-term treatment that can be translated into a reduction of suicidality and all-cause mortality. Because of preclinical evidence that it modulates neuroplasticity and prefrontal cortex connectivity, clozapine may be an interesting strategy for further severe psychotic illnesses. Nevertheless, even considering the growing use of other atypical antipsychotics in the management of bipolar disorder, a role for clozapine has been poorly defined. The clinical evidence-base for its use in this condition is largely based on uncontrolled naturalistic trials and retrospective studies and chart reviews. Several of these have supported clozapine's efficacy in treatment-resistant bipolar disorder. Possibly because of clozapine's profile of adverse effects and lack of interest from pharmaceutical companies, only two randomized trials have examined its effectiveness. Both suggest clinically relevant antimanic and mood-stabilizing properties. Therefore, the primary objective of this trial is to determine the effectiveness of clozapine for treatment-resistant bipolar disorder. Secondary objectives include examining the effects of treatment with clozapine on cognition and functioning of patients with bipolar disorder. Tolerability and safety of long-term clozapine use will also be examined. To that end, the investigators will conduct a clinical trial with 54 patients with a history of treatment resistance. Patients will be randomized to either open-label treatment with clozapine, in combination with lithium or valproate, or open-label treatment with an atypical antipsychotic with consistent evidence of efficacy in the treatment of bipolar disorder (olanzapine, quetiapine or risperidone), also in combination with lithium or valproate. Patients will be followed for one-year and time to all-cause treatment failure will be the primary outcome measure. It is the belief of the investigators that this study will generate meaningful clinical data of tremendous importance to validate clozapine as a legitimate treatment option for treatment-resistant bipolar disorder.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clozapine | Experimental | Drug: ClozapineClozapine, P.O., flexible dose, for up to 6 months |
| Risperidone, olanzapine or quetiapine | Active comparator | Drug: Risperidone, Drug: Olanzapine, Drug: QuetiapineRisperidone, olanzapine or quetiapine, according to clinical indication, flexible dose, for up to 6 months |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- DSM-IV Bipolar I Disorder;
- having had a mood episode within the preceding year; DSM-IV rapid cyclers will be permitted to participate in this study;
- males or females between 18 and 65 years of age;
- ongoing illness symptoms including significant functional impairment;
- documented history of treatment resistance, defined as persistent symptoms despite simultaneous, adequate treatment with at least two medications: one mood stabilizer (lithium or valproate) + antipsychotic OR two mood stabilizers (at least one of them being lithium or valproate).
Key exclusion criteria (7 listed)
- patients with onset of illness after age 40 or illness resulting from secondary causes
- women who are pregnant or breastfeeding, or not using adequate contraception
- unstable medical illnesses
- clinically significant abnormal laboratory tests
- current active alcohol or substance abuse
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 |
|---|---|---|
| ClozapineAlso: ClozarilFlexible dosage, with up-titration according to standard schedules employed for schezophrenia | Drug | Clozapine |
| RisperidoneAlso: RisperdalRisperidone, in a flexible dosage | Drug | Risperidone, olanzapine or quetiapine |
| OlanzapineAlso: ZyprexaOlanzapine, flexible dosage | Drug | Risperidone, olanzapine or quetiapine |
| QuetiapineAlso: SeroquelQuetiapine, flexible dosage | Drug | Risperidone, olanzapine or quetiapine |
Primary outcome
Functioning according to Functioning Assessment Short-Test
Time frame: 6 month follow up
Global functioning according to Functioning Assessment Short-Test
1 secondary outcome
Time to all-cause treatment failure
Time frame: Six months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2018.
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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.
PEDRO V MAGALHAES, M.D., Ph.D. principal investigator
Hospital de Clínicas de Porto Alegre / Universidade Federal do Rio Grande do Sul
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 Clozapine, Risperidone and Olanzapine in people with Bipolar Disorder, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
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 6 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 2 Oct 2018. 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 Brazil. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact PEDRO V MAGALHAES, M.D., Ph.D. (+555191123773, pedromaga2@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functioning according to Functioning Assessment Short-Test (time frame: 6 month follow up). 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 2 Oct 2018.