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Trial registered on ANZCTR


Registration number
ACTRN12618001965291
Ethics application status
Approved
Date submitted
21/11/2018
Date registered
5/12/2018
Date last updated
5/02/2020
Date data sharing statement initially provided
5/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Oral Ketamine Trial on Post-Traumatic Stress Disorder
Scientific title
An open-label, dose ranging, clinical trial of oral ketamine, an NMDA (N-methyl-D-aspartate) receptor antagonist, with weekly dosing over six weeks in patients who are experiencing post-traumatic stress disorder (PTSD)
Secondary ID [1] 296523 0
CTN ID: CT-2018-CTN-03765-1 v1, Protocol: AU/1/7867310.
Universal Trial Number (UTN)
U1111-1224-3868
Trial acronym
OKTOP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post-traumatic stress disorder 310305 0
Condition category
Condition code
Mental Health 309038 309038 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be administered a sub-anaesthetic oral dose of ketamine once a week for a period of 6 weeks. The initial dose will be 0.5mg per kilogram, after which dose amounts will be increased by between 0.1mg and 0.5mg/kg in each treatment, with a maximum dose of 3.0mg/kg. Upon reaching 3.0mg/kg, participants will continue at that level until the end of the treatment phase, provided they tolerate the dose, i.e. “endure the action of ketamine without any side effect or discomfort” . In comparison, the intravenous dose range for anaesthetic induction is approximately 1.0-4.0mg/kg (at approximately 0.5mg/kg/minute)

Participants may be unable to tolerate a specific dose due to physical adverse effects and psychotomimetic effects, as described below. This may occur as the dose is titrated upward or while the patient is maintaining their maximum dose. If a participant is not able to tolerate any dose due to psychological and physical side effects, their dose will be reduced to the previous treatment dose with the rest of the treatment phase maintained at that level or with further reductions if necessary. For example, if a participant is given 3.0mg/kg ketamine and does not tolerate the dose, the dose will be reduced (by 0.1-0.5mg/kg) for the rest of the treatment phase. Before each treatment, we will assess the participant to ensure that they tolerated the previous dose and to justify the dosage amount for that particular day.

The participant’s vital signs will be recorded approximately 30 minutes prior to the ketamine dose and after treatment every 30 minutes, up until 60 minutes after the dosing. Participants will be observed and monitored by a psychiatrist and/or registered nurse from the administration of the medication to the final vital sign check.

Ketamine will be administered by the psychiatrist on a routine basis but can be administered by the nurse practitioner as directed by the psychiatrist.

Two follow-up assessments will be conducted post-ketamine treatment. They are defined below:
Follow-up 1 (time point 07A): rating scales, pathology, MRI, EEG, and cognitive assessments to be conducted + 1 -10 days of treatment 6
Follow-up 2 (time point 08A): rating scales, pathology, MRI, EEG, and cognitive assessments to be conducted + 26 - 32 days of treatment 6
Intervention code [1] 312834 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 307998 0
To examine and explore the effectiveness of oral ketamine, an NMDA (N-methyl-D-aspartate) receptor antagonist, in patients who are experiencing post-traumatic stress disorder (PTSD). Change in PTSD will be assessed using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Post-traumatic Stress Disorder Checklist (PCL-5). A reduction in PTSD as determined by these scales is the primary outcome measure of this study.
Timepoint [1] 307998 0
The CAPS-5 will be collected at three time points: during initial assessment (time point 00A), and both follow-up time points (07A, 08A).

The PCL-5 will be collected at the following time points: initial assessment (00A), during weekly pre-treatment, during both phone calls, and both follow-up time points (07A, 08A).
Secondary outcome [1] 353617 0
To examine and explore the tolerability of oral ketamine, an NMDA (N-methyl-D-aspartate) receptor antagonist, in patients who are experiencing PTSD. Tolerability will be examined by assessing participant's vital signs, conducting urinalysis, blood samples, and using rating scales to assess dissociation and mania, bladder and urinary symptoms, and general side effects. Rating scales used for this outcome: Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS) The Brief Psychiatric Rating Scale (BPRS) Young Mania Rating Scale (YMRS) The Patient Rated Inventory of Side Effects (PRISE) Frequency, Intensity, and Burden of Side Effects Rating Scale (FIBSER)
Timepoint [1] 353617 0
Vital signs, urinalysis, dissociation and mania scales will be collected every treatment visit (Week 1 - week 6). Blood tests will be collected at baseline (00A), week 3 (03B), and follow up 1 and 2 (07A, 08A).
Secondary outcome [2] 353618 0
Neurological measures will be conducted at baseline, week 6 and week 10
Timepoint [2] 353618 0
MRI and EEG will be used to explore electrophysiological and functional brain changes. A cognitive battery will be used to capture changes in cognitive functioning. MRI, EEG, and the cognitive battery will be conducted at baseline (00A), and follow up 1 and 2 (07A, 08A)

Eligibility
Key inclusion criteria
Inclusion criteria: • Patients with PTSD as the primary presenting complaint, determined by the CAPS-5 and PCL-5
• 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
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
• Persons with a history of ketamine use disorder will be excluded
• Persons with a current substance use disorder will be excluded
• Persons who have recovered from a substance use disorder within 6 months or less of joining the trial will be excluded.

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Data will be transcribed from the hard copy scales used in the clinic into SPSS Statistics Software for analysis. The time to remission and improvement will be analysed using Kaplan-Meier survival analysis and a linear mixed model.

Recruitment
Recruitment status
Not yet 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] 24625 0
4575 - Birtinya

Funding & Sponsors
Funding source category [1] 301108 0
University
Name [1] 301108 0
University of the Sunshine Coast Mind and Neuroscience Thompson Institute
Address [1] 301108 0
12 Innovation Parkway, Birtinya, Queensland, 4575
Country [1] 301108 0
Australia
Primary sponsor type
University
Name
University of the Sunshine Coast Mind and Neuroscience Thompson Institute
Address
12 Innovation Parkway, Birtinya, Queensland, 4575
Country
Australia
Secondary sponsor category [1] 300719 0
None
Name [1] 300719 0
Address [1] 300719 0
Country [1] 300719 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301858 0
Prince Charles Hospital Human Research Ethics Committee
Ethics committee address [1] 301858 0
Building 14
Rode Road
CHERMSIDE QLD 4032
Ethics committee country [1] 301858 0
Australia
Date submitted for ethics approval [1] 301858 0
27/07/2018
Approval date [1] 301858 0
06/09/2018
Ethics approval number [1] 301858 0
Project ID: 42836. HREC/18/QPCH/288:

Summary
Brief summary
This study is an open-label, dose-ranging clinical trial aiming to explore the effectiveness, feasibility and tolerability of oral ketamine on post-traumatic stress disorder (PTSD). The pathology and neurobiology of PTSD will be examined via MRI and EEG as neurological measures. The Cambridge Neuropsychological Test Automated Battery. (CANTAB) will be used to measure cognitive functioning. The primary outcome of change in PTSD will be assessed using the CAPS-5 and PCL-5.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88342 0
Dr Adem Can
Address 88342 0
University of the Sunshine Coast Mind and Neuroscience Thompson Institute
12 Innovation Parkway, Birtinya QLD, 4575
Country 88342 0
Australia
Phone 88342 0
+61 7 5430 1285
Fax 88342 0
Email 88342 0
acan@usc.edu.au
Contact person for public queries
Name 88343 0
Dr Adem Can
Address 88343 0
University of the Sunshine Coast Mind and Neuroscience Thompson Institute
12 Innovation Parkway, Birtinya QLD, 4575
Country 88343 0
Australia
Phone 88343 0
+61 7 5430 1285
Fax 88343 0
Email 88343 0
acan@usc.edu.au
Contact person for scientific queries
Name 88344 0
Dr Adem Can
Address 88344 0
University of the Sunshine Coast Mind and Neuroscience Thompson Institute
12 Innovation Parkway, Birtinya QLD, 4575
Country 88344 0
Australia
Phone 88344 0
+61 7 5430 1285
Fax 88344 0
Email 88344 0
acan@usc.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results