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Trial registered on ANZCTR


Registration number
ACTRN12616001096448
Ethics application status
Approved
Date submitted
4/08/2016
Date registered
12/08/2016
Date last updated
23/01/2020
Date data sharing statement initially provided
10/12/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Ketamine for Adult Depression Study
Scientific title
Effectiveness of ketamine therapy among patients with treatment-resistant depression: a double-blind, randomised, controlled trial
Secondary ID [1] 289886 0
RG150699
Universal Trial Number (UTN)
Trial acronym
KADS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder 299230 0
Condition category
Condition code
Mental Health 299238 299238 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Ketamine. During 4-week RCT and 4-week open label extension phase with 1 month break between the two phases, A follow up is scheduled 1 month after the end of RCT where participants will be further screened for eligibility (as per RCT criteria) to enter the open label phase with the only difference being that participants are not blinded to the drug administered.

Ketamine (concentration 100mg/mL) will be administered via subcutaneous injection twice weekly for 4 weeks in each phase. Starting dose will range between 0.22-0.53 mL depending on body weight.

41-45 kg 0.22 mL
46-50 kg 0.24 mL
51-55 kg 0.27 mL
56-60 kg 0.29 mL
61-70 kg 0.33 mL
71-80 kg 0.38 mL
81-90 kg 0.43 mL
91-100 kg 0.48 mL
>100 kg 0.53 mL

Adherence will be self apparent as study personnel will administer the intervention in person via injection,

The dose may be increased depending on progress and tolerability of side effects. Upper limit of intervention drug depends on body weight but the maximum is 0.91 mL.
Intervention code [1] 295114 0
Treatment: Drugs
Comparator / control treatment
Active control drug.

A follow up is scheduled 1 month after the end of the RCT phase where participants will be further screened for eligibility to enter the open label phase in which participants are guaranteed of receiving ketamine.
Control group
Active

Outcomes
Primary outcome [1] 298721 0
Remission at end of RCT phase (score <10 on MADRS)
Timepoint [1] 298721 0
4 weeks post randomisation (End of RCT phase)
8 weeks post randomisation (4 week follow up)
12 weeks post randomisation (8 week follow up)
Secondary outcome [1] 325047 0
Depression, assessed using change in MADRS score.
Timepoint [1] 325047 0
Over 4 weeks post randomisation (each treatment session in RCT phase and End of RCT phase) 8 weeks post randomisation (4 week follow up) 12 weeks post randomisation (8 week follow up)
Secondary outcome [2] 325048 0
Study rater's assessment of depression severity, assessed using Clinician Global Impressions- Severity (CGI- S)
Timepoint [2] 325048 0
4 weeks post randomisation (End of RCT phase)
8 weeks post randomisation (4 week follow up)
12 weeks post randomisation (8 week follow up)
Secondary outcome [3] 325049 0
Hamilton Anxiety Rating Scale (HAM-A)
Timepoint [3] 325049 0
4 weeks post randomisation (End of RCT phase)
8 weeks post randomisation (4 week follow up)
12 weeks post randomisation (8 week follow up)
Secondary outcome [4] 325050 0
Change in MADRS item 10 suicidality score
Timepoint [4] 325050 0
At time of randomisation (Baseline RCT phase)
4 weeks post randomisation (End of RCT phase)
Secondary outcome [5] 325052 0
Psychotomimetic symptoms - 5 item positive symptoms subscale Brief Psychiatric Rating Scale (BPRS), Clinician Administered Dissociative States Scale (CADSS)
Timepoint [5] 325052 0
Measured at each treatment visit - twice per week for 4 weeks in RCT and twice per week for 4 weeks in open label extension phase
Secondary outcome [6] 325054 0
Suicide ideation and risk, assessed using the Columbia Suicide Severity Rating Scale (CSSR)
Timepoint [6] 325054 0
Measured at each treatment visit and assessment points:
At time of randomisation (RCT Baseline)
4 weeks post randomisation (End of RCT phase)
8 weeks post randomisation (4 week follow up)
12 weeks post randomisation (8 week follow up)

Secondary outcome [7] 325055 0
Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS)
Timepoint [7] 325055 0
4 weeks post randomisation (End of RCT phase) and at8 weeks post randomisation (4 week follow up)
Secondary outcome [8] 325056 0
Cognitive scores assessed using the Cogstate computerised test battery
Timepoint [8] 325056 0
4 weeks post randomisation (End of RCT phase)
Secondary outcome [9] 325058 0
Ketamine craving (or abuse) assessed via questionnaire designed specifically for study
Timepoint [9] 325058 0
4 weeks post randomisation (End of RCT phase)
8 weeks post randomisation (4 week follow up)
Secondary outcome [10] 325060 0
Assessment of Quality of Life (AQoL-8D)
Timepoint [10] 325060 0
4 weeks post randomisation (End of RCT phase)
Secondary outcome [11] 325061 0
Cost-utility analysis, based on AQoL and Health Economics Questionnaire (HEQ)
Timepoint [11] 325061 0
4 weeks post randomisation (End of RCT phase)
Secondary outcome [12] 325062 0
Ketamine plasma concentrations assessed via blood samples
Timepoint [12] 325062 0
At time of randomisation (Baseline) and 4 hours post first injection
Secondary outcome [13] 326035 0
Heart rate using automatic sphygmomanometer
Timepoint [13] 326035 0
Measured before treatment session and at 15 mins, 1 hour and 2 hours after injection at each treatment session, Session are twice per week for 4 weeks in RCT and twice per week for 4 weeks in open label extension phase.
Secondary outcome [14] 326036 0
Liver Function Tests assessed from blood sample:
- Aspartate aminotransferase (AST)
- Alanine aminotransferase (ALT)
Gamma-glutamyl transferase (GGT)
- Total bilirubin
Timepoint [14] 326036 0
4 weeks post randomisation (End of RCT phase)
Secondary outcome [15] 326503 0
Proportion of participants with at least 50% reduction in MADRS.
Timepoint [15] 326503 0
4 weeks post randomisation (End of RCT phase)
8 weeks post randomisation (4 week follow up)
12 weeks post randomisation (8 week follow up)
Secondary outcome [16] 326504 0
Study rater's impression of the participant's improvement in depressive symptoms measured by Clinical Global Impression - Improvement
Timepoint [16] 326504 0
4 weeks post randomisation (End of RCT phase)
8 weeks post randomisation (4 week follow up)
12 weeks post randomisation (8 week follow up)
Secondary outcome [17] 326505 0
Biomarkers e.g. biomarker of neuroplasticity - brain derived neurotrophic factor (BDNF) assessed via blood samples
Timepoint [17] 326505 0
4 weeks post randomisation (End of RCT phase)
Secondary outcome [18] 326507 0
blood pressure using automatic sphygmomanometer
Timepoint [18] 326507 0
Measured before treatment session and at 15 mins, 1 hour and 2 hours after injection at each treatment session, Sessions are twice per week for 4 weeks in RCT and twice per week for 4 weeks in open label extension phase.
Secondary outcome [19] 342120 0
Proportion of participants meeting criterion for remission (MADRS < 10).
Timepoint [19] 342120 0
Proportion of participants meeting the criterion for remission at two consecutive ratings in weeks 1 to 4 during the RCT phase. Ratings are conducted twice a week during the RCT phase.
Secondary outcome [20] 342121 0
Proportion of participants meeting the criterion for response (improvement in MADRS score from baseline of at least 50%).
Timepoint [20] 342121 0
Proportion of participants meeting the criterion for response at two consecutive ratings during weeks 1-4 of the RCT phase. Ratings are done twice a week during the RCT phase.

Eligibility
Key inclusion criteria
Criteria assessed by the research team include:
-Major Depressive Disorder (MDD) for at least 3 months.
-An inadequate response to at least 2 adequate antidepressants courses. Stable dose of antidepressant medications at least 4 weeks prior to trial entry.
-Montgomery Asberg Depression Rating Scale (MADRS) score of at least 20.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Criteria assessed by the research team to determine suitability include:
- Psychotic disorder.
- Bipolar disorder.
-Medical and neurologic conditions.
-Psychiatric disorders other than MDD.
-Planned major changes to psychotropic medication.
-Planned or probable use of ECT.
-Risk of suicide.
-Substance use, abuse, dependence.
-Recent or planned ketamine treatment.
-Medical conditions in which use of ketamine or sedating medications may pose a significant health risk.
-Women of childbearing potential not taking reliable contraception.
- inability to complete the trial

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)
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 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Suspended
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)
NSW

Funding & Sponsors
Funding source category [1] 293900 0
Government body
Name [1] 293900 0
NHMRC
Address [1] 293900 0
National Health and Medical Research Council GPO Box 1421 Canberra ACT 2601
Country [1] 293900 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
UNSW Sydney, NSW 2052, Australia
Country
Australia
Secondary sponsor category [1] 292724 0
None
Name [1] 292724 0
Address [1] 292724 0
Country [1] 292724 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295453 0
Sydney Local Health Disctict HREC
Ethics committee address [1] 295453 0
Research Ethics and Governance Office (REGO)
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 295453 0
Australia
Date submitted for ethics approval [1] 295453 0
Approval date [1] 295453 0
21/07/2016
Ethics approval number [1] 295453 0

Summary
Brief summary
The aim of this study is to determine if a course of ketamine is an effective therapy for depression. The study will also determine if repeated ketamine doses: 1) are safe, tolerable and feasible in outpatient settings; 2) provide sustained antidepressant benefits; 3) improve anxiety, suicidal ideation and health related quality of life; 4) are a cost effective treatment. 200 participants will be recruited across 6 sites in Australia (Black Dog Institute, Sydney; Royal Prince Alfred Hospital, Sydney; Monash Alfred Psychiatry Research Centre, Melbourne; South Eastern Private Hospital, Noble Park; Royal Adelaide Hospital, Adelaide; Gold Coast University Hospital, Gold Coast) and 1 in New Zealand (Dunedin, Otago). The study is a randomised controlled trial. Participants will be randomised to receive repeated doses of ketamine or a comparator treatment. For all participants, a follow-up assessment after finishing the randomised controlled phase will assess eligibility for an open label extension phase. All participants will be followed up after exiting the trial to assess treatment effects.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66854 0
Prof Collen Loo
Address 66854 0
Black Dog Institute, Hospital Road, Randwick NSW Australia 2031
Country 66854 0
Australia
Phone 66854 0
+61 2 9382 2987
Fax 66854 0
+61 2 9382 8208
Email 66854 0
ket.study@unsw.edu.au
Contact person for public queries
Name 66855 0
Dr Angelo Alonzo
Address 66855 0
Black Dog Institute, Hospital Road, Randwick NSW Australia 2031
Country 66855 0
Australia
Phone 66855 0
+61 2 9382 2987
Fax 66855 0
Email 66855 0
ket.study@unsw.edu.au
Contact person for scientific queries
Name 66856 0
Prof Colleen Loo
Address 66856 0
Black Dog Institute, Hospital Road, Randwick NSW Australia 2031
Country 66856 0
Australia
Phone 66856 0
+61 2 9382 2987
Fax 66856 0
+61 2 9382 8208
Email 66856 0
ket.study@unsw.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