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Trial registered on ANZCTR


Registration number
ACTRN12615000573550
Ethics application status
Approved
Date submitted
21/05/2015
Date registered
3/06/2015
Date last updated
5/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled study of an N-Methyl-D-Aspartate antagonist in major depression
Scientific title
A randomised, double blind, active placebo-controlled crossover trial to evaluate the short term efficacy of an N-Methyl-D-Aspartate antagonist for patients with treatment resistant depression
Secondary ID [1] 286248 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 294304 0
Major depressive disorder 295202 0
Condition category
Condition code
Mental Health 294627 294627 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Ketamine IV. – bolus dose 0.25mg/kg then infusion at 0.25 mg/kg/hr for 45 minutes
Washout 3 weeks. Follow-ups at 1,7,14,21 days.
Study duration 42 days.
Intervention code [1] 291266 0
Treatment: Drugs
Comparator / control treatment
Remifentanil IV. 0.1 ng /ml according to the Minto pharmacokinetic model for 8 minutes
Control group
Active

Outcomes
Primary outcome [1] 294390 0
Montomery-Asberg Depressive Rating Scale (MADRS)
Timepoint [1] 294390 0
4 hours post administration
Secondary outcome [1] 313183 0
BDNF plasma concentration
Timepoint [1] 313183 0
4 hours post intervention
Secondary outcome [2] 314963 0
Functional connectivity measured with electroencephalography (EEG)
Timepoint [2] 314963 0
4 hours 30 minutes

Eligibility
Key inclusion criteria
* Participant is willing and able to give informed consent for participation in the trial.
* Male or female, aged 18 years or above and less than 60.
* In the Investigators’ opinion, is able and willing to comply with all trial requirements.
* Major depressive disorder for at least three months, as assessed by a Clinical Interview using DSM-IV criteria
* MADRS >20
* An inadequate response to at least two antidepressants courses (Antidepressant Treatment History Form) one of which can include the current episode
* Stable on antidepressant medication for four weeks prior to Study Day 1
Minimum age
18 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Female participant who is pregnant, lactating or planning pregnancy during the course of the trial.
* Significant renal or hepatic impairment.
* Cardiovascular conditions including abnormal heart rate and blood pressure checked at screening.
* Participants who have participated in another research trial involving an investigational product in the past 12 weeks.
* History of psychosis
* Any unstable medical or neurologic condition.
* Planned major changes to psychotropic medication.
* Imminent risk of suicide as determined by the CSSRS.
* Planned or probable use of ECT.
* Substance abuse or dependence in previous 6 months.
* Any history of abuse of ketamine or phencyclidine.
* Contraindication to the use of ketamine according to manufacturer guidelines.
* Planned use of ketamine, for example, for pain control.
* Unable to fast for four hours prior to each administration of trial drug.
* Any other condition judged by the treating clinician as likely to impact on the ability of the participant to complete the trial.
* Body-weight <50kg or >120kg.
* Current use of NMDA antagonist medications (e.g. memantine / amantadine / rimantadine / lamotrigine / dextromethorphan/procyclidine).
* Inability to speak or read English.
* Contraindications for MRI scanning

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Crossover
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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 outside Australia
Country [1] 6685 0
New Zealand
State/province [1] 6685 0

Funding & Sponsors
Funding source category [1] 290809 0
Government body
Name [1] 290809 0
Royal Society of New Zealand
Address [1] 290809 0
11 Turnbull St,
Thorndon,
Wellington 6011
Country [1] 290809 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
Private Bag 92019
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 289496 0
None
Name [1] 289496 0
Address [1] 289496 0
Country [1] 289496 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292435 0
HDEC Northern
Ethics committee address [1] 292435 0
Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington, 6011
Ethics committee country [1] 292435 0
New Zealand
Date submitted for ethics approval [1] 292435 0
10/03/2015
Approval date [1] 292435 0
14/05/2015
Ethics approval number [1] 292435 0

Summary
Brief summary
Depression is the most prevalent mental health disorder in New Zealand. Although many treatments are available
for approximately one third of patients these treatments will be ineffective and they will be classified as "treatment-resistant".
New research indicates that the approved medicine ketamine given at low doses can be used successfully as antidepressant in approximately two thirds of patients with treatment resistant depression. Moreover ketamine’s rapid antidepressant
actions, within several hours, make it remarkable compared to usual therapies. In addition to offering hope to patients, for scientists studying depression ketamine allows new
opportunities to study the disease. In this study we will give patients with treatment-resistant depression ketamine
to rapidly move them from a state of depression to nondepression. We will use brain imaging technologies and
blood biomarkers to attempt to understand what processes occur in these patients that underlie the transition to
elevated mood.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 55266 0
Dr Suresh Muthukumaraswamy
Address 55266 0
School of Pharmacy
The University of Auckland
Private Bag 92019
Auckland 1142
Country 55266 0
New Zealand
Phone 55266 0
+64 9373 7599 ext:85398
Fax 55266 0
Email 55266 0
sd.muthu@auckland.ac.nz
Contact person for public queries
Name 55267 0
Dr Suresh Muthukumaraswamy
Address 55267 0
School of Pharmacy
The University of Auckland
Private Bag 92019
Auckland 1142
Country 55267 0
New Zealand
Phone 55267 0
+64 9373 7599 ext:85398
Fax 55267 0
Email 55267 0
sd.muthu@auckland.ac.nz
Contact person for scientific queries
Name 55268 0
Dr Suresh Muthukumaraswamy
Address 55268 0
School of Pharmacy
The University of Auckland
Private Bag 92019
Auckland 1142
Country 55268 0
New Zealand
Phone 55268 0
+64 9373 7599 ext:85398
Fax 55268 0
Email 55268 0
sd.muthu@auckland.ac.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary