NCT01977300

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
159

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jan 2003

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2003

Completed
8.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2011

Completed
2.2 years until next milestone

First Submitted

Initial submission to the registry

October 22, 2013

Completed
15 days until next milestone

First Posted

Study publicly available on registry

November 6, 2013

Completed
Last Updated

November 20, 2015

Status Verified

October 1, 2013

Enrollment Period

8.6 years

First QC Date

October 22, 2013

Last Update Submit

November 19, 2015

Conditions

Bipolar I Disorder

Outcome Measures

Primary Outcomes (1)

  • 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.

    52 weeks

Secondary Outcomes (2)

  • Time to manic episode.

    52 weeks

  • Time to depressive episode

    52 weeks

Study Arms (3)

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).

Drug: ValproateDrug: LithiumOther: 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.

Drug: ValproateDrug: LithiumDrug: RisperidoneDrug: OlanzapineOther: Placebo

"52 week" arm

ACTIVE COMPARATOR

Continuation of the atypical antipsychotic, risperidone or olanzapine, plus lithium or valproate for 52 weeks.

Drug: ValproateDrug: LithiumDrug: RisperidoneDrug: Olanzapine

Interventions

ValproateDRUG

serum level of 50 to 125 ug/L

Also known as: Valproic Acid
"52 week" arm'24 week " armMood stabilizer & Placebo
LithiumDRUG

serum levels of 0.6 to 1.2 mmol/L

Also known as: Lithium Carbonate
"52 week" arm'24 week " armMood stabilizer & Placebo
RisperidoneDRUG

1 to 6 mg/day

Also known as: Risperdal
"52 week" arm'24 week " arm
OlanzapineDRUG

5 to 25 mg/day

Also known as: Zyprexa
"52 week" arm'24 week " arm
PlaceboOTHER

manufactured to mimic risperidone and olanzapine

Also known as: Sugar Pill
'24 week " armMood stabilizer & Placebo

Eligibility Criteria

Age17 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of British Columbia

Vancouver, British Columbia, V6T 2A1, Canada

Location

Related Publications (1)

  • 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.

    PMID: 26460229BACKGROUND

MeSH Terms

Interventions

Valproic AcidLithiumLithium CarbonateRisperidoneOlanzapineSugars

Intervention Hierarchy (Ancestors)

Pentanoic AcidsValeratesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsFatty Acids, VolatileFatty AcidsLipidsMetals, AlkaliElementsInorganic ChemicalsMetals, LightMetalsCarbonatesAlkaliesCarbonic AcidCarbon Compounds, InorganicLithium CompoundsPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsBenzodiazepinesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingCarbohydrates

Study Officials

  • Lakshmi N Yatham, Dr.

    University of British Columbia

    PRINCIPAL INVESTIGATOR

  • Serge Beaulieu, Dr.

    McGill University, Montreal

    STUDY DIRECTOR

  • Andree Daigneault, Dr.

    Clinique des Maladies Affectives, Montreal

    STUDY DIRECTOR

  • Verinder Sharma, Dr.

    Regional Mental Health Care London, Ont.

    STUDY DIRECTOR

  • Hubert Wong, Dr.

    University of British Columbia

    STUDY DIRECTOR

  • Ayal Schaffer, Dr.

    Sunnybrook Health Sciences Centre, Toronto, Ont.

    STUDY DIRECTOR

  • Sagar Parikh, Dr.

    Centre for Addiction and Mental Health, Toronto, Ont.

    STUDY DIRECTOR

  • Philippe Baruch, Dr.

    Clinique des troubles de l'humeur, Quebec

    STUDY DIRECTOR

  • Peter Silverstone, Dr.

    University of Alberta

    STUDY DIRECTOR

  • Roumen Milev, Dr.

    Providence Continuing Care, Kingston, Ont.

    STUDY DIRECTOR

  • Ram Veluri, Dr.

    Northern Health Research Inc., Sudbury, Ont.

    STUDY DIRECTOR

  • Pablo Cervantes, Dr.

    Montreal General, Quebec

    STUDY DIRECTOR

  • Claire O'Donovan, Dr.

    Mental Health Services, Halifax, NS

    STUDY DIRECTOR

  • Flavio Kapczinski, Dr.

    Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil

    STUDY DIRECTOR

  • Benny Lafer, Dr.

    Instituto de Psiquiatria do Hospital das ClĂ­nicas, Sao Paulo, Brazil

    STUDY DIRECTOR

  • Angelo B Miralha da Cunha, Dr.

    Santa Maria, Brazil

    STUDY DIRECTOR

  • Joao Quevedo, Dr.

    Casa de Saude do Rio Maina Ltda, Criciuma, Brazil

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 22, 2013

First Posted

November 6, 2013

Study Start

January 1, 2003

Primary Completion

August 1, 2011

Study Completion

August 1, 2011

Last Updated

November 20, 2015

Record last verified: 2013-10

Locations

CA(1)