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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626000475347
Ethics application status
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Approved
Date submitted
Help: Date submitted
18/03/2026
Date registered
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16/04/2026
Date last updated
Help: Date last updated
16/04/2026
Date data sharing statement initially provided
Help: Data sharing statement date
16/04/2026
Type of registration
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Prospectively registered

Titles & IDs
Public title
A pilot study of Behaviour Activation Therapy combined with ketamine treatment for people with treatment-resistant depression
Scientific title
COBAT Pilot: evaluation of the feasibility of implementation, acceptability, and preliminary marginal effectiveness of Co-adapted Behaviour Activation as an adjunct to ketamine for Treatment-resistant depression.
Additional trial identifiers [1] 316421 0
Nil
Universal Trial Number (UTN)
Trial acronym
Related trial records

Health condition
Health condition(s) studied:
Treatment-resistant depression 340523 0
Condition category
Condition code
Mental Health 336725 336725 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
A co-produced behaviour activation therapy used as an adjunct to ketamine for treatment-resistant depression (BA-KET).

The BA-KET intervention will be administered over an 8-week period by an AHPRA approved psychologist or supervised provisional psychologist, There are a total of 8-10 therapy sessions, alongside the current 8-week standard ketamine treatment protocols used at study sites. There are three components to the manualised BA-KET therapy:
1. The Therapist Manual
2. The Patient Manual
3. The Patient Journal/Workbook

Within the BA-KET manual there are 7 core tasks or aims, which utilise 9 worksheets. The core tasks and aims include:

Task 1: Notice – Understanding My Depression
• Aim 1: Learn how depression works and how the participant’s behaviour affects their mood.
Task 2: Track – Monitoring My Daily Life
• Aim 2: Build awareness of what helps or hurts the participants mood.
Task 3: Explore – Identifying My Values
• Aim 3: Reconnect with what really matters to the participant.
Task 4: Plan – Turning Values into Action
• Aim 4: Take small, realistic steps that build momentum.
Task 5: Connect – Strengthening My Relationships
• Aim 5: Rebuild safe, supportive connections.
Task 6: Grow – Consolidating My Progress
• Aim 6: Recognise what’s working and build confidence.
Task 7: Maintain – Planning for the Future
• Aim 7: Prepare for ups and downs with a plan that keeps the participant safe and steady after discharge.

The Therapist Manual is designed to provide therapists with enough information to help conduct sessions and guide patients through the core tasks of BA-KET. The Patient Manual provides a more user-friendly guide for participants to use to help remind them of what they are aiming to do with each task. It is designed to reduce patient burden, while giving them enough information to be useful. The Patient Workbook/Journal has empty versions of the worksheets which can be photocopied and revisited as they work through the tasks under the guidance of their therapist.
Core components as described in the Therapist Manual:
• BATAK-D is designed as an 8–10 session program, delivered in parallel with repeat-dose ketamine treatment. Each session typically lasts 45–60 minutes, with flexibility to adapt to the patient’s needs and clinical setting. Sessions are structured, with clear goals and worksheets, but the therapist is encouraged to adjust pacing and emphasis depending on patient progress, energy, and engagement. The lived-experience co-design team felt flexibility in the delivery time and method would help reduce the barriers to completing BA. The only consensus was that therapy would not do well during ketamine treatments. Obviously, there will be limitations within your service model and according to therapist schedules, so this conversation is best had prior to beginning treatment, in collaboration with patients. The first session must be conducted prior to beginning ketamine treatment whenever possible. We recommend the first two sessions be completed prior to beginning ketamine treatment to ensure adequate time to complete a formulation and practice activity monitoring.
• Subsequent sessions are usually scheduled weekly and when possible, coordinated with patient preferences around ketamine dosing days.
• We recommend you wait at least 4 hours after ketamine dosing, before a BA session.
• We also recommend you avoid BA sessions immediately before ketamine treatments, to reduce cognitive load or potential psychosocial stressors prior to treatment. At least an hour break is recommended to allow the patient to process information and ground themselves prior to dosing with ketamine.
• Otherwise, BA sessions may be conducted at any time around ketamine treatments.
• Sessions are suitable to be conducted in-person or via teleconference.

The Therapy Roadmap (and worksheets), as described in the Therapist Manual:
Step 1 – Orientation & Preparation
o Learn how ketamine and Behavioural Activation work together.
Meet your therapist, learn about your depression, and prepare your journal.
o Worksheet 1: depression formulation
Step 2 – Monitoring My Days
o Record what you do and how you feel. No judgment — just noticing patterns.
o Worksheet 2: Activity monitoring
Step 3 – Understanding My Cycles
o Spot when avoidance keeps you stuck and when small actions help.
o Worksheet 3: Vicious Cycles
Step 4 – Exploring My Values
o Identify what really matters to you across work, health, relationships, hobbies, and daily life.
o Worksheet 4: Life Areas and Values
Step 5 – Planning Activities
o Turn your values into small, achievable actions.
o Worksheet 5: Activity List
Step 6 – Strengthening Connection
o Map your support network and plan safe, meaningful contact with others.
o Worksheet 6: My Connection Map
o Worksheet 7: My Connection Activities
Step 7 – Consolidating Progress
o Review what’s worked, celebrate small wins, notice early warning signs.
Step 8 – Planning for the Future
o Create your Relapse Prevention Plan and gather your ongoing supports.
o Worksheet 8: Relapse Awareness Checklist
o Worksheet 9: Relapse Prevention Plan

TREATMENT ADHERENCE
- will be montired using the Behavioural Activation for Depression Scale long form (BADS-LF).

KETAMINE TREATMENTS
- Ketamine treatments are being conducted as per the standard treatment protocols at each site.
- Ketamine treatments are not the intervention being investigated, and thus ketamine treatment algorithms are not being standardised, but rather are being used as per naturalistic protocols.
- The dose, treatment frequency, and route of administration varies at each site, including esketamine nasal spray, subcutaneous ketamine injection, and intravenous ketamine infusion.
- an 8-week program of ketamine treatments will be used.
- All treatments are administered in clinics and thus, treatment adherence is assessed by attendance to scheduled treatment sessions.
Intervention code [1] 333083 0
Behaviour
Intervention code [2] 333577 0
Treatment: Other
Description of the comparator or control
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 344239 0
The acceptability of the BA-KET intervention
Timepoint [1] 344239 0
- baseline (within 2 days of starting BAT, and pre-first dose of ketamine treatment,), - 4 weeks after starting first behavioural activation session, prior to receiving week 5 dose of ketamine) - 8 weeks (primary endpoint) - within a week of completing final behavioural activation session, after completion of final ketamine treatment - 1 month follow-up (12 weeks) - 4 weeks after final Behavioural activation session.
Primary outcome [2] 344240 0
The feasibility of the BA-KET intervention
Timepoint [2] 344240 0
- baseline (within 2 days of starting BAT, and pre-first dose of ketamine treatment,), - 4 weeks after starting first behavioural activation session, prior to receiving week 5 dose of ketamine) - 8 weeks (primary endpoint) - within a week of completing final behavioural activation session, after completion of final ketamine treatment - 1 month follow-up (12 weeks) - 4 weeks after final Behavioural activation session.
Primary outcome [3] 344241 0
The preliminary effectiveness of the BA-KET intervention
Timepoint [3] 344241 0
- baseline (within 2 days of starting BAT, and pre-first dose of ketamine treatment,), - 4 weeks after starting first behavioural activation session, prior to receiving week 5 dose of ketamine) - 8 weeks (primary endpoint) - within a week of completing final behavioural activation session, after completion of final ketamine treatment - 1 month follow-up (12 weeks) - 4 weeks after final Behavioural activation session.
Secondary outcome [1] 457936 0
Adoption of the BA-KET intervention.
Timepoint [1] 457936 0
- baseline (within 2 days of starting BAT, and pre-first dose of ketamine treatment,), - 8 weeks - within a week of completing final behavioural activation session, after completion of final ketamine treatment
Secondary outcome [2] 457938 0
Depression
Timepoint [2] 457938 0
- baseline (within 2 days of starting BAT, and pre-first dose of ketamine treatment,), - 4 weeks after starting first behavioural activation session, prior to receiving week 5 dose of ketamine) - 8 weeks - within a week of completing final behavioural activation session, after completion of final ketamine treatment - 1 month follow-up (12 weeks) - 4 weeks after final Behavioural activation session.
Secondary outcome [3] 457939 0
Suicidality
Timepoint [3] 457939 0
- baseline (within 2 days of starting BAT, and pre-first dose of ketamine treatment,), - 4 weeks after starting first behavioural activation session, prior to receiving week 5 dose of ketamine) - 8 weeks (endpoint) - within a week of completing final behavioural activation session, after completion of final ketamine treatment - 1 month follow-up (12 weeks) - 4 weeks after final Behavioural activation session.
Secondary outcome [4] 457940 0
Anxiety
Timepoint [4] 457940 0
- baseline (within 2 days of starting BAT, and pre-first dose of ketamine treatment,), - 4 weeks after starting first behavioural activation session, prior to receiving week 5 dose of ketamine) - 8 weeks (endpoint) - within a week of completing final behavioural activation session, after completion of final ketamine treatment - 1 month follow-up (12 weeks) - 4 weeks after final Behavioural activation session.
Secondary outcome [5] 457941 0
Participant-identified costs of the intervention
Timepoint [5] 457941 0
- baseline (within 2 days of starting BAT, and pre-first dose of ketamine treatment,), - 8 weeks - within a week of completing final behavioural activation session, after completion of final ketamine treatment
Secondary outcome [6] 457942 0
Adoption of BA-KET intervention
Timepoint [6] 457942 0
- baseline (within 2 days of starting BAT, and pre-first dose of ketamine treatment,), - 4 weeks after starting first behavioural activation session, prior to receiving week 5 dose of ketamine) - 8 weeks (endpoint) - within a week of completing final behavioural activation session, after completion of final ketamine treatment

Eligibility
Key inclusion criteria
Adults with treatment resistant depression defined as inadequate response to at least two different antidepressants of adequate dose and duration in the current major depressive episode.

Aged 18 years or over

Assessed by clinic psychiatrist as eligible to receive clinical ketamine treatment,

Assessed by clinic psychiatrist as eligible to receive Behavioural Activation Therapy

Can attend Behavioural Activation Therapy sessions

Depression score equal to or greater than 20 at commencement of treatment (using MADRS depression interview)

Able to provide written informed consent for research study
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
Unable to give informed consent,

At high risk of harm to self or others,

Unable to understand the intervention or complete clinic consent processes in English

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
20/04/2026
Actual
Date of last participant enrolment
Anticipated
8/03/2027
Actual
Date of last data collection
Anticipated
31/05/2027
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 29149 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 29150 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 45455 0
2050 - Camperdown
Recruitment postcode(s) [2] 45456 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 321027 0
Government body
Name [1] 321027 0
Australian Department of Health, Disability and Ageing, Medical Research Future Fund (MRFF)
Country [1] 321027 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Country
Australia
Secondary sponsor category [1] 323890 0
None
Name [1] 323890 0
Address [1] 323890 0
Country [1] 323890 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 319563 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 319563 0
Ethics committee country [1] 319563 0
Australia
Date submitted for ethics approval [1] 319563 0
27/01/2026
Approval date [1] 319563 0
16/03/2026
Ethics approval number [1] 319563 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 147722 0
Dr Dean Wright
Address 147722 0
The University of Sydney, Professor Marie Bashir Centre, 67-73 Missenden Road, CAMPERDOWN NSW 2050 Australia
Country 147722 0
Australia
Phone 147722 0
+61 2 9515 1440
Fax 147722 0
Email 147722 0
[email protected]
Contact person for public queries
Name 147723 0
Dean Wright
Address 147723 0
The University of Sydney, Professor Marie Bashir Centre, 67-73 Missenden Road, CAMPERDOWN NSW 2050 Australia
Country 147723 0
Australia
Phone 147723 0
+61 2 9515 1440
Fax 147723 0
Email 147723 0
[email protected]
Contact person for scientific queries
Name 147724 0
Dean Wright
Address 147724 0
The University of Sydney, Professor Marie Bashir Centre, 67-73 Missenden Road, CAMPERDOWN NSW 2050 Australia
Country 147724 0
Australia
Phone 147724 0
+61 2 9515 1440
Fax 147724 0
Email 147724 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.