Condition category
Mental and Behavioural Disorders
Date applied
05/12/2011
Date assigned
09/12/2011
Last edited
28/07/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Clinical depression is one of the most common and debilitating of the psychiatric disorders. It accounts for the greatest burden of disease among all mental health problems, and is expected to become the second-highest amongst all general health problems by 2020. This is a study of two psychological interventions - Behavioural Activation (BA) and Cognitive Behaviour Therapy (CBT) - to establish whether there are important clinical and cost differences between them.

Who can participate?
Participants will be adults aged 18 and older with Major Depressive Disorder assessed through a standard clinical interview by members of the research team. We will not be able to include people who are alcohol or drug dependent, acutely suicidal, have physical health reasons for any impairments in their thinking, have a bipolar disorder or psychosis/psychotic symptoms. We will also exclude people currently receiving psychological therapy elsewhere.

What does the study involve?
BA and CBT are two psychological treatments which are recommended by guidelines for the treatment of depression. Half our participants in the COBRA trial will receive BA and half CBT, allocated on a random basis. You will receive a maximum of 20 sessions over 16 weeks with the option of four additional booster sessions. You will receive face to face sessions, of one-hour duration, with the option of session being conducted up to twice weekly over the first two months and weekly thereafter.
BA involves a structured programme of organising increased contact with positive activities and reducing people's avoidance of important situations, other people and activities. CBT identifies and modifies negative automatic thinking and unhelpful beliefs to assist people develop more help ways of thinking and behaving in everyday situations and experiences.

What are the possible benefits and risks of participating?
Both treatments are active psychological treatments which have previously demonstrated positive effects. This trial may be of benefit to people, since CBT is generally only available in the UK for 8-15% of people with depression. There are no known side effects for either treatment.

Where is the study run from?
The study will be taking place in three sites: Devon, Durham and Leeds with the lead centre being the University of Exeter's Mood Disorders Centre.

When is the study starting and how long is it expected to run for?
The study will begin in March 2012, the first participant will start treatment in September 2012 and the study will end in April 2016. Participants will be recruited from August 2012 until April 2014.

Who is funding the study?
The trial is funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme Clinical Evaluation and Trials grant.

Who is the main contact?
Professor David Richards
d.a.richards@exeter.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof Dave Richards

ORCID ID

Contact details

Mood Disorders Centre
College of Life & Environmental Studies
Washington Singer Building
University of Exeter
Perry Road
Exeter
EX4 4QG
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HTA 10/50/14

Study information

Scientific title

COBRA (Cost and Outcome of BehaviouRal Activation): a two-arm Phase III, non-inferiority, patient level, randomised controlled trial of behavioural activation versus cognitive behaviour therapy

Acronym

COBRA

Study hypothesis

Clinical depression is one of the most common and debilitating of the psychiatric disorders. Lifetime prevalence has been estimated at 16.2% and rates of co-morbidity are high. Without treatment, up to 1/3 of all patients will have episodes that last longer than two years, and over 3/4 of all patients who recover from one episode will go on to have at least one more.

Depression is therefore a major health problem which causes substantial disability and is set to become the second largest cause of global disability by 2020. In the UK depression and anxiety are estimated to cost the economy £17bn in lost output and direct health care costs annually, with a £9bn impact on the Exchequer through benefit payments and lost tax receipts. Service user organisations and policy think tanks advocate psychological therapies for depression, which many patients prefer to antidepressants.

The project will seek to address two interlinked research questions:
1. What is the clinical effectiveness of Behavioural Activation (BA) compared to Cognitive Behaviour Therapy (CBT) for depressed adults in terms of depression treatment response measured by the PHQ9 at six, 12 and 18 months?
2. What is the cost-effectiveness of BA compared to CBT at 18 months?

We hypothesise that BA is non-inferior compared to CBT in reducing depression severity but that BA will be less costly and thus more cost-effective than CBT.

More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/105014
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0018/55440/PRO-10-50-14.pdf

Ethics approval

Not provided at time of registration

Study design

Two-arm phase III non-inferiority patient level randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

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

Condition

Depression

Intervention

Behavioural Activation (BA): participants will receive a maximum of 20 sessions over 16 weeks with the option of four additional booster sessions. Sessions will be face to face, of one-hour duration, with the option of being conducted up to twice weekly over the first two months and weekly thereafter. They will consist of a structured programme increasing contact with potentially antidepressant environmental reinforcers through scheduling and reducing the frequency of negatively reinforced avoidant behaviours. Treatment will be based on a shared formulation drawn from the behavioural model in the early stages of treatment, thereafter developed with the patient throughout their sessions. Specific BA techniques include the use of a functional analytical approach to develop a shared understanding with patients of behaviours that interfere with meaningful, goal-oriented behaviours and include self monitoring, identifying 'depressed behaviours', developing alternative goal orientated behaviours and scheduling. In addition the role of avoidance and rumination will be addressed through functional analysis and alternative response development. Mental health workers delivering BA will follow a revised treatment manual based on that used in our Phase II trial and previous international studies

Cognitive Behaviour Therapy (CBT): participants will receive a maximum of 20 sessions over 16 weeks with the option of four additional booster sessions. Sessions will be face to face, of one-hour duration, with the option of being conducted up to twice weekly over the first two months and weekly thereafter. They will consist of a structured, partially didactic programme. Treatment begins with patients learning the model, behavioural change techniques, and moves on to to identifying and modidfying negative automatic thoughts, maladaptive beliefs and underlying core beliefs. In later sessions, learning is translated to anticipating and practicing the management of stressors that could provoke relapse in the future. Specific CBT techniques include scheduling activity and mastery behaviours, the use of thought records and modifying maladaptive beliefs. Therapists delivering CBT will follow a treatment protocol based on the standard manuals published by Beck and colleagues.

Intervention type

Behavioural

Phase

Drug names

Primary outcome measures

Self-reported depression severity as measured by the PHQ9 at 12 & 18 months adjusting for baseline outcome values and stratification variables (symptom severity, site, antidepressant use) and fitting therapist as a random effects variable

Secondary outcome measures

1. Secondary process evaluation to investigate the moderating, mediating and procedural factors in BA and CBT which influence outcome
2. Direct and indirect costs of treatment and disease burden
3. Health-state utility (EQ5D)
4. DSM depression status and depression free days (SCID)
5. Health Related Quality of Life (SF-36)
6. Six month interim analysis on PHQ9

Overall trial start date

05/03/2012

Overall trial end date

05/03/2016

Reason abandoned

Eligibility

Participant inclusion criteria

1. Persons aged 18 and older and over (no upper age limit) with Major Depressive Disorder (DSM) assessed by standard clinical interview [Structured Clinical Interview for Depression (SCID)]
2. Researchers will be trained to administer the SCID using established training and inter-rater reliability procedures that are in use at the Mood Disorders Centre for all the trials

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

440 participants (220 in each arm)

Participant exclusion criteria

1. Persons who are alcohol or drug dependent, acutely suicidal or cognitively impaired
2. Have a bipolar disorder or psychosis/psychotic symptoms, ascertained by baseline research interviews
3. People currently in receipt of psychological therapy

Recruitment start date

01/08/2012

Recruitment end date

01/04/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Exeter
Exeter
EX4 4QG
United Kingdom

Sponsor information

Organisation

University of Exeter (UK)

Sponsor details

c/o Dr Michael Wykes
Research & Knowledge Transfer
Innovation Centre
Rennes Drive
Exeter
EX4 4RN
United Kingdom

Sponsor type

University/education

Website

http://www.exeter.ac.uk/research/excellence/researchandknowledgetransfer/

Funders

Funder type

Government

Funder name

Health Technology Assessment Programme (Ref: 10/50/14)

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

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

2014 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/24447460
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/27461440

Publication citations

  1. Protocol

    Rhodes S, Richards DA, Ekers D, McMillan D, Byford S, Farrand PA, Gilbody S, Hollon SD, Kuyken W, Martell C, O'Mahen HA, O'Neill E, Reed N, Taylor RS, Watkins ER, Wright KA, Cost and outcome of behavioural activation versus cognitive behaviour therapy for depression (COBRA): study protocol for a randomised controlled trial., Trials, 2014, 15, 29, doi: 10.1186/1745-6215-15-29.

  2. Results

    Richards DA, Ekers D, McMillan D, Taylor RS, Byford S, Warren FC, Barrett B, Farrand PA, Gilbody S, Kuyken W, O'Mahen H, Watkins ER, Wright KA, Hollon SD, Reed N, Rhodes S, Fletcher E, Finning K, Cost and Outcome of Behavioural Activation versus Cognitive Behavioural Therapy for Depression (COBRA): a randomised, controlled, non-inferiority trial, Lancet, 2016, pii: S0140-6736(16)31140-0, doi: 10.1016/S0140-6736(16)31140-0.

Additional files

Editorial Notes

28/07/2016: Publication reference added.