Condition category
Mental and Behavioural Disorders
Date applied
10/01/2008
Date assigned
29/02/2008
Last edited
26/10/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.cequel.org

Contact information

Type

Scientific

Primary contact

Prof John Geddes

ORCID ID

Contact details

Department of Psychiatry
Warneford Hospital
Oxford
OX3 7JX
United Kingdom
+44 (0)1865 226480
john.geddes@psych.ox.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

MRC ref: 81651; OCTUMI-02:CEQUEL

Study information

Scientific title

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

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

Oxfordshire Research Ethics Committee B, 09/04/2008, ref: 08/H0605/39

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

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

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

Phase

Not Specified

Drug names

Quetiapine, lamotrigine

Primary outcome measures

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 trial start date

01/06/2008

Overall trial end date

05/05/2013

Reason abandoned

Eligibility

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 type

Patient

Age group

Adult

Gender

Both

Target number of participants

202

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

United Kingdom

Trial participating centre

Department of Psychiatry
Oxford
OX3 7JX
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

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

Sponsor type

University/education

Website

Http://www.ox.ac.uk

Funders

Funder type

Government

Funder name

Medical Research Council (MRC) (UK) (ref: 81651)

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2016 results: https://www.ncbi.nlm.nih.gov/pubmed/26687300

Publication citations

Additional files

Editorial Notes

26/10/2016: Publication reference added