Comparative Evaluation of QUEtiapine-Lamotrigine combination versus quetiapine monotherapy (and folic acid versus placebo) in people with bipolar depression

ISRCTN	ISRCTN17054996
DOI	https://doi.org/10.1186/ISRCTN17054996
Secondary identifying numbers	MRC ref: 81651; OCTUMI-02:CEQUEL

Submission date: 10/01/2008
Registration date: 29/02/2008
Last edited: 26/10/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Mental and Behavioural Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration

Study website

Contact information

Prof John Geddes
Scientific

Department of Psychiatry
Warneford Hospital
Oxford
OX3 7JX
United Kingdom

Phone	+44 (0)1865 226480
Email	john.geddes@psych.ox.ac.uk

Study information

Study design	Multicentre double-blind randomised placebo-controlled parallel-group, 2 x 2 factorial clinical trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Comparative Evaluation of QUEtiapine-Lamotrigine combination versus quetiapine monotherapy (and folic acid versus placebo) in people with bipolar depression
Study acronym	CEQUEL
Study hypothesis	The combination of quetiapine and lamotrigine will be more effective than quetiapine alone as treatment for acute bipolar depression. Please note that this trial has been updated since the original submission. All changes can be found in the relevant field under the update date of 28/04/2008. The previous title of this trial was 'Comparative Evaluation of QUEtiapine-Lamotrigine combination versus quetiapine monotherapy (and folic acid versus placebo) in patients with bipolar depression', and the previous anticipated start date of this trial was 01/04/2008. More details can be found at: http://www.mrc.ac.uk/ResearchPortfolio/Grant/Record.htm?GrantRef=G0700477&CaseId=9701 On 20/12/2013 the anticipated end date was changed from 31/03/2012 to 05/05/2013 and the target number of participants field was changed from 584 to 202.
Ethics approval(s)	Oxfordshire Research Ethics Committee B, 09/04/2008, ref: 08/H0605/39
Condition	Bipolar depression
Intervention	1. Open-label quetiapine (oral) plus 2. Lamotrigine (oral) or placebo plus 3. Folic acid (oral) or placebo The recommended dose of quetiapine is 300 mg/day but this can be reduced if the higher dose is not tolerated. Minimum dose 150 mg/day. Quetiapine will be taken for about 54 weeks (1-2 week run-in phase and 12 month randomised phase). The recommended dose of lamotrigine is 200 mg/day (reduced to 100 mg/day for participants taking concurrent valproic acid preparations). Lamotrigine will be taken for the 12 months randomised phase. Dose of folic acid: 500 µg/day. Folic acid will be taken for the 12 months randomised phase.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Quetiapine, lamotrigine
Primary outcome measure	Remission of depressive symptoms at 12 weeks post-randomisation.
Secondary outcome measures	1. The proportion of participants who both achieve remission by 12 weeks following randomisation (defined as a score of <= 5 on QIDS-SR16) and remain free from symptomatic relapse by 52 weeks. Depressive relapse is defined as a QIDS-SR16 score >= 10 on two consecutive weekly ratings and manic relapse as an Altman Self-Rating Mania Scale (ASRM) score of >=10 on a single weekly rating. 2. New intervention (admission or drug treatment) for manic episode by 52 weeks. 3. New intervention (admission or drug treatment) for depressive episode by 52 weeks. 4. Proportion of time over 12 months when participants were free from manic symptoms (ASRM <= 5). 5. Proportion of time over 12 months when participants were free from depressive symptoms (QIDS-SR16 <= 5). 6. Death (all cause and cause-specific including suicide). 7. Deliberate self-harm. 8. Quality of life will be assessed 4-weekly over 52 weeks (timepoints added 28/04/2008) 9. Unexpected adverse events. 10 Withdrawal from quetiapine or lamotrigine due to adverse effects. 11. Use of health and social care service resources. 12. Social costs/benefits.
Overall study start date	01/06/2008
Overall study end date	05/05/2013

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	202
Participant inclusion criteria	For the active run-in phase: 1. Primary diagnosis of bipolar disorder type I or II (based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV] criteria for a hypomanic or manic episode) 2. Consent to participate in the trial 3. Aged 16 or over 4. Current depressive episode requiring new pharmacological treatment (either as add-on therapy or as a change of treatment) 5. Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) Score >= 14 Please note that, as of 15/09/2008, inclusion criterion "1. Diagnosis of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) bipolar disorder type I or II (assessed using the Mini-International Neuropsychiatric Interview [MINI])" has been replaced with "1. Primary diagnosis of bipolar disorder type I or II (based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV] criteria for a hypomanic or manic episode)" For the randomised phase: 1. Able to tolerate quetiapine at a dose of at least 150 mg/day 2. Uncertainty whether quetiapine plus lamotrigine would be more effective than quetiapine monotherapy 3. Acceptable adherence to quetiapine (>90%) and to self-report SMS text-messages satisfactory 4. QIDS-SR16 score of >=11 on day of randomisation 5. Willing to accept random allocation of treatments 6. In the opinion of the investigator, not currently experiencing manic or mixed episode
Participant exclusion criteria	Current exclusion criteria as of 15/09/2008: 1. Definite indications or contraindications to lamotrigine, quetiapine or folic acid (Including pregnancy or planned pregnancy) 2. New course of specific psychosocial intervention started in the past four weeks 3. First appointment for specific psychosocial intervention booked within the next 14 weeks 4. Primary diagnosis of schizophrenia Plus, for women of child-bearing potential: 5. Currently breast feeding or not using adequate contraception Current exclusion criteria as of 28/04/2008: 1. Definite indications or contraindications to lamotrigine, quetiapine or folic acid (Including pregnancy or planned pregnancy) 2. New course of specific psychosocial intervention started in the past four weeks 3. First appointment for specific psychosocial intervention booked within the next 14 weeks 4. Currently meeting criteria for (hypo)mania (based on MINI) 5. Currently meeting criteria for schizophrenia 6. Eight or more mood episodes in the past year Plus, for women of child-bearing potential: 7. Not using adequate contraception Initial exclusion criteria: 1. Definite indications or contraindications to lamotrigine, quetiapine or folic acid (Including pregnancy or planned pregnancy) 2. New course of structured psychotherapy started in the past four weeks 3. First appointment for structured psychotherapy booked within the next 14 weeks 4. Currently meeting criteria for (hypo)mania (based on MINI) 5. Eight or more mood episodes in the past year Plus, for women of child-bearing potential: 6. Not using adequate contraception
Recruitment start date	01/06/2008
Recruitment end date	05/05/2013

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Department of Psychiatry

Oxford
OX3 7JX
United Kingdom

Sponsor information

University of Oxford (UK)
University/education

Clinical Trials and Research Governance
Manor House
John Radcliffe Hospital
Headington
Oxford
OX3 9DU
England
United Kingdom

Website	Http://www.ox.ac.uk
"ROR"	https://ror.org/052gg0110

Funders

Funder type

Government

Medical Research Council (MRC) (UK) (ref: 81651)
Government organisation / National government

Alternative name(s): UK Medical Research Council, MRC
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results:	01/01/2016		Yes	No

Editorial Notes

26/10/2016: Publication reference added