Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000267459p
Ethics application status
Submitted, not yet approved
Date submitted
10/02/2025
Date registered
10/04/2025
Date last updated
10/04/2025
Date data sharing statement initially provided
10/04/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Oral ketamine for bipolar depression
Scientific title
Feasibility of oral ketamine for bipolar depression: a 20-week open-label study
Secondary ID [1] 313926 0
none
Universal Trial Number (UTN)
U1111-1318-8727
Trial acronym
Linked study record
This is a follow-up study to ACTRN12623000817640 (Ketamine versus Ketamine plus Behavioural Activation Therapy for Adults with Treatment Resistant Depression) but is open-label without a therapy component.

Health condition
Health condition(s) or problem(s) studied:
Bipolar Disorder 336619 0
Bipolar depression 336708 0
Condition category
Condition code
Mental Health 333208 333208 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral ketamine will be administered twice-weekly in the clinical research units of the Departments of Psychological Medicine (Dunedin or Christchurch) for a total of 8-weeks. Each dose will be administered under the oversight of a healthcare professional. Oral ketamine dose will be determined by the MADRS and tolerability using an established protocol as follows.

Oral Ketamine to commence at 1 mg/kg mixed with 50 ml orange juice and sipped over 30–60 minutes. Initial dosing twice weekly (with gaps of 3 and 4 days between doses). If first dose is tolerated and if the Montgomery Asberg Depression Rating Scale (MADRS)>6 on follow-up (indicating mild depression or greater), increase dose to 1.5 mg/kg twice weekly. If second dose is tolerated and if the MADRS>6 on follow-up, increase dose to 2 mg/kg twice weekly. If the MADRS is <6 on follow-up, dosing can be reduced to weekly intervals. Dosing to be supervised by administering clinician (study nurse or doctor) and discussed with the supervising psychiatrist as needed and if ketamine is not tolerated.
Intervention code [1] 330516 0
Treatment: Drugs
Comparator / control treatment
This is an open-label feasibility study with no control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 340663 0
Feasibility
Assessment method [1] 340663 0
Feasibility will be determined by a composite of recruitment rate (based on inquiries leading to study enrolment), retention rate (based on completion of the study protocol), and treatment adherence (based on adherence to the ketamine dosing).
Timepoint [1] 340663 0
Recruitment will be assessed during the enrolment phase, retention will be assessed at the end of the study (week 20), and treatment adherence will be assessed at week 8 following the end of dosing.
Primary outcome [2] 340664 0
Bipolar depression
Assessment method [2] 340664 0
Montgomery Asberg Depression Rating Scale
Timepoint [2] 340664 0
baseline, weekly for the 8 weeks of ketamine dosing, fortnightly during follow-up (weeks 9-20), and the final assessment (week 20)
Primary outcome [3] 340665 0
Safety and tolerability as a composite measure
Assessment method [3] 340665 0
Young Mania Rating Scale (to monitor mood elevation with ketamine treatment), Bladder Pain/Interstitial Cystitis symptom Score (to monitor cystitis symptoms eg haematuria, dysuria, frequency), incidence of adverse and serious adverse events (eg dissociation and sedation) assessed clinically by clinical staff overseeing dosing
Timepoint [3] 340665 0
Weekly for 8 weeks during the ketamine treatment phase
Secondary outcome [1] 444730 0
Relapse
Assessment method [1] 444730 0
Montgomery Asberg Depression Rating Scale
Timepoint [1] 444730 0
Weekly following the end of 8 weeks oral dosing for 12 weeks (weeks 9-20)
Secondary outcome [2] 444731 0
Cognitive functioning
Assessment method [2] 444731 0
MATRICS Consensus Cognitive Battery
Timepoint [2] 444731 0
Baseline (prior to dosing) and week 9 (after 8-weeks ketamine treatment)
Secondary outcome [3] 444732 0
Psychomotor activity
Assessment method [3] 444732 0
Actigraphy (GENEActiv actigraphs)
Timepoint [3] 444732 0
1 week prior and 2 weeks after ketamine commences Weeks -1, 1, and 2) 1 week prior and 1 week after ketamine finishes (weeks 8,9) week 20
Secondary outcome [4] 444733 0
Depression
Assessment method [4] 444733 0
Depression Anxiety and Stress Scale-21
Timepoint [4] 444733 0
Baseline (prior to dosing), end of week 8 (after the course of ketamine treatment ends), week 20 (after the follow-up period ends)
Secondary outcome [5] 444734 0
Functioning
Assessment method [5] 444734 0
Work and Social Adjustment Scale
Timepoint [5] 444734 0
Baseline (prior to dosing), end of week 8 (after the course of ketamine treatment ends), week 20 (after the follow-up period ends)
Secondary outcome [6] 444735 0
Quality of Life
Assessment method [6] 444735 0
Brief QoL-BD
Timepoint [6] 444735 0
Baseline (prior to dosing), end of week 8 (after the course of ketamine treatment ends), week 20 (after the follow-up period ends)
Secondary outcome [7] 444736 0
Ketamine dependence
Assessment method [7] 444736 0
Severity of Dependence Scale
Timepoint [7] 444736 0
End of week 8 (after the course of ketamine treatment ends), week 20 (after the follow-up period ends)
Secondary outcome [8] 444737 0
Ketamine Dependence
Assessment method [8] 444737 0
Drug Liking and Craving Questionnaire
Timepoint [8] 444737 0
End of week 8 (after the course of ketamine treatment ends), week 20 (after the follow-up period ends)
Secondary outcome [9] 444738 0
Personality difficulties
Assessment method [9] 444738 0
PDS-ICD-11
Timepoint [9] 444738 0
Baseline (prior to dosing), end of week 8 (after the course of ketamine treatment ends), week 20 (after the follow-up period ends)
Secondary outcome [10] 444740 0
Mixed mood symptoms
Assessment method [10] 444740 0
Christchurch mixed symptoms scale
Timepoint [10] 444740 0
Baseline, weekly during treatment (weeks 1-8), week 20.

Eligibility
Key inclusion criteria
• Age 18-65 years.
• Diagnosis of Bipolar I or II Disorder according to DSM-5 (American Psychiatric Association, 2013) criteria.
• Current Major Depressive Episode according to DSM-5 (American Psychiatric Association, 2013) criteria.
• On stable psychiatric medications for at least 4 weeks prior to screening. Bipolar 1 disorder patients required to be on mood stabilising treatment (recommended doses of an antipsychotic medication, lithium carbonate, or sodium valproate). Maintenance treatment with lamotrigine only is not sufficient (because it typically has limited efficacy for preventing mood elevation) unless individual circumstances suggest there has been an extended period of stability on lamotrigine without other mood stabilisers.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• History of current or recent substance disorder within the past 6 months (excluding nicotine use disorder and mild cannabis use disorder).
• Diagnosis of primary psychotic disorder.
• Moderate-severe personality disorder.
• Severe acute or chronic medical conditions.
• Current or recent significant suicidal intent or self-harm behaviour.
• Bladder pathology.
• Inability to participate provide informed consent and/or participate in study procedures.
• Pregnancy or lactation.
• Prior serious head injury or other neurological condition causing ongoing cognitive impairment.
• Young Mania Rating Scale (YMRS) > 8 (Young et al., 1978) (to rule out mixed states).
• Previous poor response to ketamine.

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
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
23/06/2025
Actual
Date of last participant enrolment
Anticipated
22/02/2027
Actual
Date of last data collection
Anticipated
12/07/2027
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment outside Australia
Country [1] 26874 0
New Zealand
State/province [1] 26874 0

Funding & Sponsors
Funding source category [1] 318410 0
Charities/Societies/Foundations
Name [1] 318410 0
Maia Health Foundation - Sue Bradford Memorial Trust grant
Country [1] 318410 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Country
New Zealand
Secondary sponsor category [1] 320801 0
None
Name [1] 320801 0
Country [1] 320801 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 317038 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 317038 0
Ethics committee country [1] 317038 0
New Zealand
Date submitted for ethics approval [1] 317038 0
04/02/2025
Approval date [1] 317038 0
Ethics approval number [1] 317038 0

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 139794 0
A/Prof Ben Beaglehole
Address 139794 0
University of Otago, Christchurch, Department of Psychological Medicine, PO Box 4345, Christchurch 8140
Country 139794 0
New Zealand
Phone 139794 0
+64 27 212 7488
Email 139794 0
ben.beaglehole@otago.ac.nz
Contact person for public queries
Name 139795 0
Ben Beaglehole
Address 139795 0
University of Otago, Christchurch, Department of Psychological Medicine, PO Box 4345, Christchurch 8140
Country 139795 0
New Zealand
Phone 139795 0
+64 27 212 7488
Email 139795 0
ben.beaglehole@otago.ac.nz
Contact person for scientific queries
Name 139796 0
Ben Beaglehole
Address 139796 0
University of Otago, Christchurch, Department of Psychological Medicine, PO Box 4345, Christchurch 8140
Country 139796 0
New Zealand
Phone 139796 0
+64 27 212 7488
Email 139796 0
ben.beaglehole@otago.ac.nz

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• reputable research group seeking to pool data on ketamine treatment for bipolar depression

What individual participant data might be shared?
• All de-identified individual participant data
What types of analyses could be done with individual participant data?
• Systematic reviews and meta-analyses
When can requests for individual participant data be made (start and end dates)?
From:
Following publication of trial data, no planned end date

To:
-

Where can requests to access individual participant data be made, or data be obtained directly?
• By email approach to A/Prof Beaglehole: ben.beaglehole@otago.ac.nz

Are there extra considerations when requesting access to 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.