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Trial registered on ANZCTR


Registration number
ACTRN12618001412224
Ethics application status
Approved
Date submitted
25/07/2018
Date registered
23/08/2018
Date last updated
7/11/2018
Date data sharing statement initially provided
7/11/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Oral Ketamine Trial on Suicidality
Scientific title
An open-label clinical trial of oral ketamine, an NMDA (N-methyl-D-aspartate) receptor antagonist, with weekly dosing over six weeks, in 25-50 patients who are experiencing chronic suicidal ideation.
Secondary ID [1] 295441 0
CT-2018-CTN-00653-1
Universal Trial Number (UTN)
U1111-1216-8179
Trial acronym
OKTOS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic suicidality 308714 0
Condition category
Condition code
Mental Health 307655 307655 0 0
Suicide

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be administered a weekly sub anaesthetic dose of ketamine (oral liquid formulation) for six consecutive weeks beginning at 0.5mg/kg and titrated to 3.0mg/kg. Dosing will increase by 0.1 - 0.5mg/kg each week for participants who tolerate the previous dose, with dosing determined by a Psychiatrist. Dosing will be administered at the trial site under direct supervision of the Psychiatrist, and participants will be monitored for one hour by a Mental Health Nurse Practitioner or Mental Health Nurse Research Officer prior to leaving the site.
Intervention code [1] 301771 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 306644 0
To examine and explore the effectiveness of oral ketamine, an NMDA (N-methyl-D-aspartate) receptor antagonist, in patients who are experiencing chronic suicidal ideation.
Change in suicidality will be assessed using the Beck Scale for Suicide Ideation (BSS). Any reduction in suicidality as determined by this scale is the primary outcome measure of this study.
Timepoint [1] 306644 0
Suicidality will initially be assessed at baseline, and then at four time points per week during the treatment phase (week 1 to 6). The four time points are: 1) on treatments days pre-ketamine, 2) on treatments days post-ketamine, 3) one day post-ketamine, and 4) three days post-ketamine. Suicidality will then be assessed in the follow up phase once at Week 10.
Secondary outcome [1] 349103 0
In addition to investigating the effectiveness of oral ketamine on chronic suicidality, we aim to further understand the neuropathology between suicidality and depressive illnesses. MRI will be used to examine changes in resting state, brain structure, and the glutamatergic system, and EEG will be used to explore electrophysiological changes. These neurological measures will be conducted at baseline, Week 6 and Week 10.
Timepoint [1] 349103 0
Participants will undergo MRI and EEG assessments at the Initial Assessment (prior to ketamine treatment), at Week 6 (following the completion of ketamine treatment), and at Week 10 (4 weeks after the completion of ketamine treatment).
Secondary outcome [2] 350732 0
To examine and explore the tolerability of oral ketamine, an NMDA (N-methyl-D-aspartate) receptor antagonist, in patients who are experiencing chronic suicidal ideation. Tolerability will be examined by assessing participant's vital signs, conducting urinalysis, and using rating scales to assess dissociation and mania, bladder and urinary symptoms, and general side effects.
Timepoint [2] 350732 0
Urinalysis will be conducted at six time points, prior to each treatment (week 1 to 6). Vital signs will be assessed at 19 time points (once at baseline, and on treatment days - once prior to each treatment and twice post-treatment). Rating scales will be used at three times points per week during the treatment phase (week 1 to 6) and once at the completion of the follow-up phase (week 10).
Secondary outcome [3] 350985 0
In addition to investigating the effectiveness and tolerability of oral ketamine on chronic suicidality, we aim to explore the feasibility of using this treatment protocol and dosing regimen for a greater period of time in an extension study.
Timepoint [3] 350985 0
This secondary outcome will be considered feasible if our target enrolment (n=25) is achieved during the trial's funded period (i.e. within 24 months), and clinically significant reductions in suicidality and tolerability of the treatment are observed during the pilot study.

Eligibility
Key inclusion criteria
• Patients with chronic suicidal thoughts as the primary presenting complaint, determined by a score of greater than or equal to 6 for the Scale for Suicide Ideation (BSS)
• Persons (male/female/other) aged over 18 years
• Participant to receive physical examination from Principal Investigator within 14 days prior to commencement of ketamine treatment to eliminate possibility of conditions outlined in
exclusion criteria
• Participants must be able to understand the PIF and provide written informed consent on the Participant Consent Form (PCF)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Persons under 18 years of age
• Psychosis
• Mania/hypomania
• Acute suicidality requiring urgent psychiatric intervention
• Uncontrolled/severe symptomatic cardiovascular disease states including: recent myocardial infarction (within prior 6 months); history of stroke; and hypertension (resting blood pressure >150/100)
• History of intracranial mass, intracranial haemorrhage/stroke, cerebral trauma/traumatic brain injury or increased intracranial pressure (as assessed by referring general practitioner)
• Liver function test (LFT) results that exceed the upper level of normal range by 3 times
• Previous reaction to ketamine (as reported by referring general practitioner and participant)
• Pregnant women
• Breastfeeding women

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 24629 0
4575 - Birtinya

Funding & Sponsors
Funding source category [1] 300032 0
Government body
Name [1] 300032 0
Commonwealth Government, Department of Health
Address [1] 300032 0
Department of Health, GPO Box 48 Brisbane, Queensland 4001 Australia
Country [1] 300032 0
Australia
Primary sponsor type
University
Name
Sunshine Coast Mind and Neuroscience - Thompson Institute, University of the Sunshine Coast
Address
12 Innovation Parkway, Birtinya QLD 4575
Country
Australia
Secondary sponsor category [1] 299420 0
None
Name [1] 299420 0
Address [1] 299420 0
Country [1] 299420 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300881 0
Bellberry Limited Human Research Ethics Committee C
Ethics committee address [1] 300881 0
129 Glen Osmond Road, Eastwood, South Australia 5063
Ethics committee country [1] 300881 0
Australia
Date submitted for ethics approval [1] 300881 0
Approval date [1] 300881 0
26/04/2018
Ethics approval number [1] 300881 0
2017-12-982
Ethics committee name [2] 300897 0
Human Research Ethics Committee of the University of the Sunshine Coast
Ethics committee address [2] 300897 0
90 Sippy Downs Dr,
Sippy Downs QLD 4556
Ethics committee country [2] 300897 0
Australia
Date submitted for ethics approval [2] 300897 0
Approval date [2] 300897 0
24/05/2018
Ethics approval number [2] 300897 0
A181101

Summary
Brief summary
This study is an open-label clinical trial aiming to explore the effectiveness, feasibility and tolerability of oral ketamine on suicidality. The pathology and neurobiology of suicidality will be examined via MRI and EEG as neurological measures. The primary outcome of change in suicidality will be assessed using the Beck Scale for Suicide Ideation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85142 0
Dr Adem Can
Address 85142 0
Sunshine Coast Mind and Neuroscience - Thompson Institute
12 Innovation Parkway, Birtinya QLD 4575
Country 85142 0
Australia
Phone 85142 0
+61 7 5430 1191
Fax 85142 0
Email 85142 0
Adem.Can@research.usc.edu.au
Contact person for public queries
Name 85143 0
Dr Adem Can
Address 85143 0
Sunshine Coast Mind and Neuroscience - Thompson Institute
12 Innovation Parkway, Birtinya QLD 4575
Country 85143 0
Australia
Phone 85143 0
+61 7 5430 1191
Fax 85143 0
Email 85143 0
Adem.Can@research.usc.edu.au
Contact person for scientific queries
Name 85144 0
Dr Adem Can
Address 85144 0
Sunshine Coast Mind and Neuroscience - Thompson Institute
12 Innovation Parkway, Birtinya QLD 4575
Country 85144 0
Australia
Phone 85144 0
+ 61 7 5430 1191
Fax 85144 0
Email 85144 0
Adem.Can@research.usc.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
This has not been discussed previously by the research team.
What supporting documents are/will be available?
No other documents available
Summary results
No Results