Bipolar I DisorderPhase 3NCT01977300
Atypical Antipsychotics for Continuation and Maintenance Treatment After an Acute Manic Episode
A Phase 3 study testing Valproate, Lithium and Risperidone in people with Bipolar I Disorder, run by University of British Columbia at 1 site in Canada.
Trial summary
Hypothesis: Continuation of an atypical antipsychotic medication in combination with a Mood Stabilizer, following remission from an acute manic episode, lowers the rates of relapse and recurrence of mood episodes compared to discontinuing the antipsychotics within days of resolution of manic symptoms. Read more about this study
- Who is it for?
- Ages 17 years and older
- Conditions the study is for
- Bipolar I Disorder
- What is being tested?
- Valproate, Lithium and Risperidone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 159 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2003to Aug 2011
- Phase
- Phase 3
- 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 17 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients who were recently (within the last 12 weeks) commenced on treatment for a Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) manic or mixed episode with a combination of lithium and risperidone, lithium and olanzapine, valproate and risperidone, or valproate and olanzapine;
- Patients on 1 to 6 mg of risperidone or 5 to 25 mg of olanzapine
- Patients who are in remission from mania for at least 2 weeks but no more than 6 weeks and have maintained remission for 2 consecutive weeks;
- Patients must not be taking any other psychotropic medication (with the exception of benzodiazepines) or treatments including bromocriptine, omega 3 fatty acids, Axid or EMPower;
- Patients aged 17 and above.
Who cannot join
- Any subjects who do not meet the above inclusion criteria will be excluded from the study.
- In order for the findings to be generalizable to clinically representative patients with bipolar disorder, any patients with a history of co-morbid substance abuse or medical illnesses will not be excluded.
Trial locations and contacts
1 site in 1 country.
Canada1 site
University of British Columbia
Vancouver, British Columbia, V6T 2A1
About this study
Hypothesis: Continuation of an atypical antipsychotic medication in combination with a Mood Stabilizer, following remission from an acute manic episode, lowers the rates of relapse and recurrence of mood episodes compared to discontinuing the antipsychotics within days of resolution of manic symptoms.
Read the detailed description
This is a randomised, double-blind, placebo controlled trial over 52 weeks. Patients will be on one of four combinations of medications at the time of entry into the study: a) lithium and risperidone, b) lithium and olanzapine, c) valproate and risperidone, or d) valproate and olanzapine. After obtaining informed consent, patients will be randomised to one of three groups 1)"0" week group: patients will receive lithium or valproate plus placebo for 52 weeks (risperidone or olanzapine tapering will begin on the day of randomisation with discontinuation of the drug within 2 weeks), 2) continuation of the same atypical antipsychotic, risperidone or olanzapine, plus lithium or valproate for 24 weeks (tapering of the antipsychotic begins at the end of 24 weeks and completed within 2 weeks) followed by the same mood stabilizer plus placebo for another 28 weeks, and 3) continuation of the atypical antipsychotic, risperidone or olanzapine, plus lithium or valproate for 52 weeks. The duration of the double-blind phase of the study will be 52 weeks and all patients will continue on the mood stabilizer, lithium or valproate, they had been on during the acute mania for the full duration of the study. The serum level of the mood stabilizer will be maintained within the therapeutic range (0.6 to 1.2 mmol/L for lithium and 50 to 125 ug/L for valproate) throughout the 52 weeks as determined by blood tests. The dose and the type of atypical antipsychotic (ie risperidone or olanzapine) each patient will receive during the double-blind period will be the same that the patient had been on at the time of entry into the double-blind phase. All patients, irrespective of which treatment arm they are in, will receive active psychoeducation and counselling regarding sleep hygiene, healthy daily routines and rhythms, alcohol and substance abuse, anxiety management, conflict resolution and problem solving as clinically indicated in routine clinical practice. Patients who withdraw from or meet a primary end point of the study will be treated actively as done in regular clinical practice.
Patients will not be allowed to receive any other psychotropic medication with the exception of benzodiazepines for sedation and anti-parkinsonian medication for extrapyramidal side effects. The doses of these will be recorded.
- Conditions
- Bipolar I Disorder
- Being tested
- Valproate, Lithium, Risperidone, Olanzapine, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ValproateDrug
Also called Valproic Acid
serum level of 50 to 125 ug/L
LithiumDrug
Also called Lithium Carbonate
serum levels of 0.6 to 1.2 mmol/L
RisperidoneDrug
Also called Risperdal
1 to 6 mg/day
OlanzapineDrug
Also called Zyprexa
5 to 25 mg/day
PlaceboOther
Also called Sugar Pill
manufactured to mimic risperidone and olanzapine
| Study group | Role | What they receive |
|---|---|---|
| Mood stabilizer & Placebo | Placebo comparator | Patients will receive lithium or valproate plus placebo for 52 weeks (risperidone or olanzapine tapering will begin on the day of randomization with discontinuation of the drug within 2 weeks). Receives: Drug: Valproate; Drug: Lithium; Other: Placebo |
| '24 week " arm | Experimental | Continuation of the lithium or valproate plus risperidone or olanzapine for 24 weeks followed by mood stabilizer plus placebo for another 28 weeks. Dosages: 1 to 6 mg of risperidone, 5 to 20 mg olanzapine. Receives: Drug: Valproate; Drug: Lithium; Drug: Risperidone; Drug: Olanzapine; Other: Placebo |
| "52 week" arm | Active comparator | Continuation of the atypical antipsychotic, risperidone or olanzapine, plus lithium or valproate for 52 weeks. Receives: Drug: Valproate; Drug: Lithium; Drug: Risperidone; Drug: Olanzapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome measure is the time to any mood episode (depressive or manic episode).
A mood episode is defined as 1) Young Mania Rating Scale (YMRS) score of 15 or greater 2)Hamilton Rating Scale for Depression (HAM-D) 21-item score of 15 or greater or a HAM-D suicide item score of 3 or greater 3)A Clinical Global Impression -Severity (CGI-S) score of 3 or greater 4) a patient requiring hospitalization for treatment of mood symptoms or 5) a patient who makes a suicide attempt or commits suicide during the study.
Measured: 52 weeks
Secondary outcomes (2)
Time to manic episode.
Time to occurrence of a manic episode measured by Young Mania Rating Scale (YMRS) score of 15 or greater .
Measured: 52 weeks
Time to depressive episode
Time to occurrence of a depressive episode measured by Hamilton Rating Scale for Depression (HAM-D) 21-item score of 15 or greater or a HAM-D suicide item score of 3 or greater.
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2013 (estimated)
- Study startJan 2003
- Primary completionAug 2011
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bipolar I DisorderStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 159 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Eli Lilly and Company, Janssen-Ortho Inc., Canada
- Responsible party
- Sponsor
- Investigators
- Lakshmi N Yatham, Dr., Principal investigator, University of British ColumbiaSerge Beaulieu, Dr., Study director, McGill University, MontrealAndree Daigneault, Dr., Study director, Clinique des Maladies Affectives, MontrealVerinder Sharma, Dr., Study director, Regional Mental Health Care London, Ont.Hubert Wong, Dr., Study director, University of British ColumbiaAyal Schaffer, Dr., Study director, Sunnybrook Health Sciences Centre, Toronto, Ont.Sagar Parikh, Dr., Study director, Centre for Addiction and Mental Health, Toronto, Ont.Philippe Baruch, Dr., Study director, Clinique des troubles de l'humeur, Quebec
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01977300
- Sponsor's protocol ID
- H02-70188
- Other IDs
- V02-0130
- Status last verified
- Oct 2013
- First submitted
- 22 Oct 2013
- Last updated
- 20 Nov 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Yatham LN, Beaulieu S, Schaffer A, Kauer-Sant'Anna M, Kapczinski F, Lafer B, Sharma V, Parikh SV, Daigneault A, Qian H, Bond DJ, Silverstone PH, Walji N, Milev R, Baruch P, da Cunha A, Quevedo J, Dias R, Kunz M, Young LT, Lam RW, Wong H. Optimal duration of risperidone or olanzapine adjunctive therapy to mood stabilizer following remission of a manic episode: A CANMAT randomized double-blind trial. Mol Psychiatry. 2016 Aug;21(8):1050-6. doi: 10.1038/mp.2015.158. Epub 2015 Oct 13.
PubMed 26460229
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Atypical Antipsychotics for Continuation and Maintenance Treatment After an Acute Manic Episode
- ClinicalTrials.gov ID
- NCT01977300
- Acronym / sponsor ID
- H02-70188
- Conditions
- Bipolar I Disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 159 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Eli Lilly and Company, Janssen-Ortho Inc., Canada
- Study start
- Jan 2003
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 6 Nov 2013 (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.
Hypothesis: Continuation of an atypical antipsychotic medication in combination with a Mood Stabilizer, following remission from an acute manic episode, lowers the rates of relapse and recurrence of mood episodes compared to discontinuing the antipsychotics within days of resolution of manic symptoms.
Detailed description
This is a randomised, double-blind, placebo controlled trial over 52 weeks. Patients will be on one of four combinations of medications at the time of entry into the study: a) lithium and risperidone, b) lithium and olanzapine, c) valproate and risperidone, or d) valproate and olanzapine. After obtaining informed consent, patients will be randomised to one of three groups 1)"0" week group: patients will receive lithium or valproate plus placebo for 52 weeks (risperidone or olanzapine tapering will begin on the day of randomisation with discontinuation of the drug within 2 weeks), 2) continuation of the same atypical antipsychotic, risperidone or olanzapine, plus lithium or valproate for 24 weeks (tapering of the antipsychotic begins at the end of 24 weeks and completed within 2 weeks) followed by the same mood stabilizer plus placebo for another 28 weeks, and 3) continuation of the atypical antipsychotic, risperidone or olanzapine, plus lithium or valproate for 52 weeks. The duration of the double-blind phase of the study will be 52 weeks and all patients will continue on the mood stabilizer, lithium or valproate, they had been on during the acute mania for the full duration of the study. The serum level of the mood stabilizer will be maintained within the therapeutic range (0.6 to 1.2 mmol/L for lithium and 50 to 125 ug/L for valproate) throughout the 52 weeks as determined by blood tests. The dose and the type of atypical antipsychotic (ie risperidone or olanzapine) each patient will receive during the double-blind period will be the same that the patient had been on at the time of entry into the double-blind phase. All patients, irrespective of which treatment arm they are in, will receive active psychoeducation and counselling regarding sleep hygiene, healthy daily routines and rhythms, alcohol and substance abuse, anxiety management, conflict resolution and problem solving as clinically indicated in routine clinical practice. Patients who withdraw from or meet a primary end point of the study will be treated actively as done in regular clinical practice.
Patients will not be allowed to receive any other psychotropic medication with the exception of benzodiazepines for sedation and anti-parkinsonian medication for extrapyramidal side effects. The doses of these will be recorded.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Mood stabilizer & Placebo | Placebo comparator | Drug: Valproate, Drug: Lithium, Other: PlaceboPatients will receive lithium or valproate plus placebo for 52 weeks (risperidone or olanzapine tapering will begin on the day of randomization with discontinuation of the drug within 2 weeks). |
| '24 week " arm | Experimental | Drug: Valproate, Drug: Lithium, Drug: Risperidone, Drug: Olanzapine, Other: PlaceboContinuation of the lithium or valproate plus risperidone or olanzapine for 24 weeks followed by mood stabilizer plus placebo for another 28 weeks. Dosages: 1 to 6 mg of risperidone, 5 to 20 mg olanzapine. |
| "52 week" arm | Active comparator | Drug: Valproate, Drug: Lithium, Drug: Risperidone, Drug: OlanzapineContinuation of the atypical antipsychotic, risperidone or olanzapine, plus lithium or valproate for 52 weeks. |
Who may qualify
- Ages
- 17 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Patients who were recently (within the last 12 weeks) commenced on treatment for a Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) manic or mixed episode with a combination of lithium and risperidone, lithium and olanzapine, valproate and risperidone, or valproate and olanzapine;
- Patients on 1 to 6 mg of risperidone or 5 to 25 mg of olanzapine
- Patients who are in remission from mania for at least 2 weeks but no more than 6 weeks and have maintained remission for 2 consecutive weeks;
- Patients must not be taking any other psychotropic medication (with the exception of benzodiazepines) or treatments including bromocriptine, omega 3 fatty acids, Axid or EMPower;
- Patients aged 17 and above.
Key exclusion criteria (2 listed)
- Any subjects who do not meet the above inclusion criteria will be excluded from the study.
- In order for the findings to be generalizable to clinically representative patients with bipolar disorder, any patients with a history of co-morbid substance abuse or medical illnesses will not be excluded.
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 |
|---|---|---|
| ValproateAlso: Valproic Acidserum level of 50 to 125 ug/L | Drug | "52 week" arm, '24 week " arm, Mood stabilizer & Placebo |
| LithiumAlso: Lithium Carbonateserum levels of 0.6 to 1.2 mmol/L | Drug | "52 week" arm, '24 week " arm, Mood stabilizer & Placebo |
| RisperidoneAlso: Risperdal1 to 6 mg/day | Drug | "52 week" arm, '24 week " arm |
| OlanzapineAlso: Zyprexa5 to 25 mg/day | Drug | "52 week" arm, '24 week " arm |
| PlaceboAlso: Sugar Pillmanufactured to mimic risperidone and olanzapine | Other | '24 week " arm, Mood stabilizer & Placebo |
Primary outcome
The primary outcome measure is the time to any mood episode (depressive or manic episode).
Time frame: 52 weeks
A mood episode is defined as 1) Young Mania Rating Scale (YMRS) score of 15 or greater 2)Hamilton Rating Scale for Depression (HAM-D) 21-item score of 15 or greater or a HAM-D suicide item score of 3 or greater 3)A Clinical Global Impression -Severity (CGI-S) score of 3 or greater 4) a patient requiring hospitalization for treatment of mood symptoms or 5) a patient who makes a suicide attempt or commits suicide during the study.
2 secondary outcomes
Time to manic episode.
Time frame: 52 weeks
Time to depressive episode
Time frame: 52 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 20 Nov 2015.
- Background: PubMed 26460229Yatham LN, Beaulieu S, Schaffer A, Kauer-Sant'Anna M, Kapczinski F, Lafer B, Sharma V, Parikh SV, Daigneault A, Qian H, Bond DJ, Silverstone PH, Walji N, Milev R, Baruch P, da Cunha A, Quevedo J, Dias R, Kunz M, Young LT, Lam RW, Wong H. Optimal duration of risperidone or olanzapine adjunctive therapy to mood stabilizer following remission of a manic episode: A CANMAT randomized double-blind trial. Mol Psychiatry. 2016 Aug;21(8):1050-6. doi: 10.1038/mp.2015.158. Epub 2015 Oct 13.
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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.
Lakshmi N Yatham, Dr. principal investigator
University of British Columbia
Serge Beaulieu, Dr. study director
McGill University, Montreal
Andree Daigneault, Dr. study director
Clinique des Maladies Affectives, Montreal
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Valproate, Lithium and Risperidone in people with Bipolar I Disorder, 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 5 inclusion and 2 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 20 Nov 2015. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
The primary outcome measure is the time to any mood episode (depressive or manic episode). (time frame: 52 weeks). 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 NCT01977300, which also lists 1 linked publication.
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 20 Nov 2015.