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Trial registered on ANZCTR


Registration number
ACTRN12618001393246p
Ethics application status
Submitted, not yet approved
Date submitted
15/08/2018
Date registered
20/08/2018
Date last updated
9/07/2019
Date data sharing statement initially provided
9/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Ketamine in anorexia nervosa
Scientific title
Pilot study on the effects of ketamine on mood and eating disorder cognitions in enduring anorexia nervosa
Secondary ID [1] 295776 0
none
Universal Trial Number (UTN)
none
Trial acronym
none
Linked study record
none

Health condition
Health condition(s) or problem(s) studied:
anorexia nervosa 309180 0
depressive disorder 309181 0
anxiety disorder 309182 0
obessional disorder 309183 0
Condition category
Condition code
Mental Health 308055 308055 0 0
Eating disorders
Mental Health 308056 308056 0 0
Depression
Mental Health 308057 308057 0 0
Anxiety
Mental Health 308058 308058 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There are two treatment phases, an initial double-blind single dose crossover phase, and a subsequent open-label maintenance phase. All treatments/interventions will be undertaken in research treatment rooms and patients will be under direct observation of study staff.

Double-blind crossover phase (3 weeks) Patients will receive single oral doses of ketamine 0.375 mg/kg of bodyweight, ketamine 0.75 mg/kg or midazolam 0.01 mg/kg (1 dose of each) weekly over three weeks. The drugs will be administered orally. Dosing will be double blind with a balanced crossover.

Maintenance phase: patients completing the double-blind crossover phase, who have shown at least 50% improvement in depression or anxiety ratings will be eligible to enter a 3 month maintenance phase. Oral ketamine will be administered 1-2x weekly (based on durability of improvement in mood/obsessionality), using an optimised dose based on the earlier phase.
Intervention code [1] 312105 0
Treatment: Drugs
Intervention code [2] 312106 0
Treatment: Devices
Comparator / control treatment
In the double blind crossover phase patients will receive single oral doses of ketamine 0.375, 0.75 mg/kg or midazolam 0.01 mg/kg on 3 separate occasions.

Maintenance phase: Open-label oral ketamine will be administered 1-2x weekly for 3 months, using an optimised dose based on the earlier phase.
Control group
Active

Outcomes
Primary outcome [1] 307055 0
Montgomery Asberg Depression Rating Scale (MADRS),

Timepoint [1] 307055 0
Double-blind crossover phase : predose, 2, 24, 72, & 168h post-each dose
Maintenance phase: predose and 2h post-dose.
Primary outcome [2] 307099 0
Hamilton Anxiety Scale (HamA)
Timepoint [2] 307099 0
Double-blind crossover phase : predose, 2, 24, 72, & 168h post-each dose
Maintenance phase: predose and 2h post-dose.
Primary outcome [3] 307100 0
Yale-Brown-Cornell Eating-Disorder-Examination (YBC-EDE) - measuring obsessionality
Timepoint [3] 307100 0
Double-blind crossover phase : predose, 2, 24, 72, & 168h post-each dose
Maintenance phase: predose and 2h post-dose.
Secondary outcome [1] 350507 0
EEG abnormalities have been identified in the cingulate cortex in enduring anorexia nervosa. The 10 minute resting state Electroencephalogram (EEG) is to identify if such changes can be normalised after treatment with ketamine, tPNS and ISF
Timepoint [1] 350507 0
Double-blind crossover phase : predose, 2, and 24h post-each dose

Eligibility
Key inclusion criteria
* Primary diagnosis DSM 5 Anorexia Nervosa (AN) based on a structured psychiatric interview
* Illness duration of AN of greater than 5 years
* Disabling severity with substantial functional impairment
* AN treatment refractoriness, defined as lack of response to two or more typical modes of treatment, such as inpatient weight restoration, psychotherapy and /or psychopharmacology
* Severely underweight: Body Mass Index (BMI) greater than 15 and less than 18
*18-45 years old
* English speaking and able to answer the study questions fluently
* Has the mental capacity to provide written informed consent to research participation
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*Unstable physical condition (severe electrolyte disturbances, cardiac failure and other physical conditions due to low weight in which surgery/anaesthesia is contraindicated)
* Treatable underlying cause of AN/underweight
* Parkinson's disease, dementia, epilepsy
* History of schizophrenia/psychosis, bipolar disorder
* Actively suicidal - Columbia Suicide Severity Rating Scale (CSSRS) of 4 or 5
* Alcohol or substance abuse (including benzodiazepines) during the last 6 months
* Severe DSM 5 Antisocial Personality Disorder or Borderline Personality Disorder
*Females who are pregnant or lactating

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Double-blind crossover phase: Allocation is concealed from patient and rater. Allocation involves contacting the holder of the allocation schedule who is not at the administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Double-blind crossover phase: Balanced crossover of all 3 drug treatments based on a computerised random code.
Maintenance phase: open label,; no randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Other
Other design features
Double-blind crossover phase: Balanced crossover of all 3 drug treatments based on a computerised random code.
Maintenance phase: open label,; no randomisation
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Up to 24 participants will be recruited to ensure that 12 participants complete all procedures.
* Demographic and Background Characteristics: Patient demographic, background characteristics and trial data will be descriptively summarized for all subjects.
* Ketamine and midazolam pharmacodynamics: Changes in mood, obsessionality and eating disorder symptoms scores will be descriptively summarized. Changes in scores over time by treatment will be analysed using repeated measures ANOVA.
* Resting EEG analysis: log Fourier power will be calculated for eyes open and eyes closed periods separately for all electrodes. Frontal midline power, left-right alpha asymmetry, and frontal-posterior alpha asymmetry will be extracted as separate measures and each subjected to repeated measures ANOVA with effect of ketamine and midazolam treatment and eyes open/closed as factors.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/09/2019
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment outside Australia
Country [1] 20771 0
New Zealand
State/province [1] 20771 0
Dunedin, Otago

Funding & Sponsors
Funding source category [1] 300367 0
University
Name [1] 300367 0
University of Otago
Country [1] 300367 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
PO Box 56
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 299814 0
None
Name [1] 299814 0
none
Address [1] 299814 0
none
Country [1] 299814 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 301179 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 301179 0
Ethics committee country [1] 301179 0
New Zealand
Date submitted for ethics approval [1] 301179 0
10/07/2019
Approval date [1] 301179 0
Ethics approval number [1] 301179 0

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

Contacts
Principal investigator
Name 86118 0
Prof Paul Glue
Address 86118 0
Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country 86118 0
New Zealand
Phone 86118 0
+64 21 243 3372
Fax 86118 0
+ 64 3 470 9684
Email 86118 0
paul.glue@otago.ac.nz
Contact person for public queries
Name 86119 0
Shona Neehoff
Address 86119 0
Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country 86119 0
New Zealand
Phone 86119 0
+ 64 3 470 9451
Fax 86119 0
+ 64 3 470 9684
Email 86119 0
shona.neehoff@otago.ac.nz
Contact person for scientific queries
Name 86120 0
Paul Glue
Address 86120 0
Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country 86120 0
New Zealand
Phone 86120 0
+64 21 243 3372
Fax 86120 0
+ 64 3 470 9684
Email 86120 0
paul.glue@otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No data at this time; pilot study


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.