ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12616001592437

Ethics application status

Approved

Date submitted

15/11/2016

Date registered

18/11/2016

Date last updated

1/12/2017

Type of registration

Prospectively registered

Titles & IDs

Public title

Single dose ketamine pharmacokinetic-pharmacodynamic relationships in healthy volunteers

Scientific title

Single dose ketamine pharmacokinetic-pharmacodynamic relationships in healthy volunteers

Secondary ID [1]

nil known

Universal Trial Number (UTN)

Trial acronym

Early Ketamine PK-PD

Linked study record

Health condition

Health condition(s) or problem(s) studied:

major depressive disorder

post traumatic stress disorder

obsessive compulsive disorder

generalized anxiety disorder

social phobia

Condition category

Condition code

Mental Health

Depression

Mental Health

Anxiety

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Volunteers will receive a single subcutaneous injection (either saline placebo, or ketamine 0.5 or 1mg/kg).

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

saline placebo

Control group

Placebo

Outcomes

Primary outcome [1]

ketamine pharmacokinetics
Parameters assessed Cmas, AUC, Tmax
Outcome assessed by plasma assay

Timepoint [1]

timepoints are: pre-dose, 3, 6, 10, 15, 30, 45, 60, 90, 120 & 180 minutes & 24 hrs post-dose

Primary outcome [2]

Brain-derived neurotrophic factor (BDNF) pharmacokinetics
Parameters assessed Cmas, AUC, Tmax
Outcome assessed by serum assay

Timepoint [2]

timepoints are: pre-dose, 3, 6, 10, 15, 30, 45, 60, 90, 120 & 180 minutes and 24 hrs post-dose

Primary outcome [3]

Cognitive testing
Tests:
- Self rated mood (happy, sad, calm, tense, energetic, and sleepy, rated from 0 (Not at all…) to 100 (Extremely…).
- Pro assesses basic visuomotor performance (a green square appears on the left or right and subjects have to press the key on the same side as the square). Anti assesses inhibitory control (a red square appears on the left or right and subjects have to press the key on the opposite side of the square). Pro/Anti assesses switching abilities (a green or red square appears on the left or right and subjects have to press the key on the same side as green squares and on the opposite side of red squares.
- Simon assesses the ability to ignore irrelevant spatial information (one of two possible consonants appear to the left or right of centre and subjects have to indicate the identity of the consonant by pressing the assigned left or right key; thus the position of the consonant is either congruent or incongruent with the side of the correct response).
- Flanker assesses the ability to ignore irrelevant identity-based information (one of two possible consonants appear at centre and one appears above or below centre; the two consonants are either the same (congruent) or different (incongruent) and subjects have to indicate the identity of the central consonant by pressing the assigned key, with the flanking consonant to be ignored),
- Forward Spatial assesses short-term memory capacity (a computerized version of the Corsi block tapping task) that involves viewing nine boxes that light up in a predetermined random sequence followed by a tone signalling the subject to indicate the sequence using a mouse to click on boxes; each sequence length occurs twice; if the subject responds correctly to at least one of the two occurrences, the program increases the length of the sequence by one box up to a maximum length of nine boxes
- Backward Spatial assesses short-term memory manipulation (identical to Forward Spatial except that the sequence has to be recalled in the reverse order; i e., click the boxes in the opposite order to which they lit up).
- The 2-back test assesses working memory (consonants, except for W, Y, and Z, appear one at a time centred on the screen in a predetermined random sequence; subjects indicate whether each consonant matches the consonant two-back in the sequence).

Timepoint [3]

Timepoints are: pre-dose, 45 mins, 3 hours, and 24 hours post-dose

Secondary outcome [1]

This is a primary outcome
EEG
10 minute relaxation EEG - subjects will alternate once a minute between eyes open and eyes closed

Timepoint [1]

Timepoints are: pre-dose, 2hrs, 24hrs and 168 hrs post-dose

Eligibility

Key inclusion criteria

Capable of understanding and signing an informed consent
Aged > 18 years on the day of consent
Good general health
Suitable venous access

Minimum age

18 Years

Maximum age

65 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

1. Females who are or intend to become pregnant, or are lactating.
2. Participants who, in the opinion of the investigator, do not understand the information and procedures of the study, or would not be compliant with them (in particular the study restrictions and risks involved).
3. Any participant for whom the investigator believes, for any reason, that participation would not be an acceptable risk.
4. Current use of monoamine oxidase inhibitors (MAOIs), thyroxine or stimulants (amphetamine/methyphenidate)
5. Regular use of any drug that alters mood or is used to treat mental disorder, including daily use of alcohol or use of alcohol within 24 hours of testing.
6. Use of medications that may alter BDNF concentrations, including antidepressants
7. Subjects with a prior history of seizures; susceptibility to photosensitivity; or a history of allergic skin reactions.

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)

Prof Glue will create the random codes. All study personnel involved with recruitment, dosing, data collection and analysis will have no access to the random codes until the databases are locked.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Computer generated random code, with stratification based on gender

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 1

Type of endpoint/s

Pharmacokinetics / pharmacodynamics

Statistical methods / analysis

Recruitment

Recruitment status

Withdrawn

Reason for early stopping/withdrawal

Other reasons/comments

Other reasons

trial no longer necessary

Date of first participant enrolment

Anticipated

9/01/2017

Actual

Date of last participant enrolment

Anticipated

30/06/2017

Actual

Date of last data collection

Anticipated

30/06/2017

Actual

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Otago

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Otago

Address [1]

PO Box 56
Dunedin, 9054

Country [1]

New Zealand

Primary sponsor type

University

Name

University of Otago

Address

PO Box 56
Dunedin, 9054

Country

New Zealand

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southern Health and Disability Committee

Ethics committee address [1]

Ministry of  Health
PO Box 5013
Wellington 6011

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

Approval date [1]

26/08/2016

Ethics approval number [1]

16/STH/111/

Summary

Brief summary

In 2000 the NMDA antagonist ketamine was reported to be an effective fast acting antidepressant in patients with major depressive disorder (MDD), and this has subsequently been confirmed in multiple studies. In addition, single doses of ketamine, at the same dose levels, were shown to have strong effects on anxiety symptoms in patients with post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD). We have recently identified similar effects in patients with refractory Generalized Anxiety Disorder (GAD) and Social Phobia (SP) – (Study 15/STH/86). In all anxiety disorders, there were rapid (within 1h) improvements in anxiety severity that were sustained for 3-7 days, not dissimilar to the responses in patients with MDD. The dose response was also similar, suggesting that the pathophysiology of diverse negative emotional disorders (anxiety, depression) may share a common neurobiology. 
We have also been studying aspects of ketamine’s neurobiology, in particular its effects on expression of BDNF, in rats. BDNF is a neurotrophic hormone that appears to have an important general role in the activity of all antidepressants and many anxiolytics.
Another pharmacodynamic endpoint is cognition. One of the side effects of ketamine is changes in cognition, with changes in a range of cognitive domains following lower dose ketamine administration.. These changes were only present until 2 hours post-infusion. In a more recent trial delayed recall was found to be reduced at 40 minutes but a return to baseline was not assessed.. 
It is possible that ketamine’s effects on cognition are associated with its concentration in blood, and a recent review suggested that levels of 20 ng/mL could affect psychomotor performance. 
There are several objectives in this randomised double blind parallel group study:
1. To evaluate the early and later effects of single doses of ketamine on BDNF concentrations in healthy volunteers, and to explore the relationship of BDNF changes with ketamine and metabolite concentrations. This research may help inform biomarker research in patient populations.
2. To evaluate the early and late effects of ketamine on EEG changes 
3. To evaluate the magnitude and duration of cognitive changes following a dose of ketamine or placebo in healthy volunteers. Blood testing will also show any associations of cognitive changes with levels of ketamine and its metabolites in the participant’s bloodstream. This research may help to improve the administration method for ketamine in a clinical setting.

Trial website

none

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Paul Glue

Address

Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054

Country

New Zealand

Phone

+64 21 243 3372

Fax

paul.glue@otago.ac.nz

Contact person for public queries

Name

Shona Neehoff

Address

Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054

Country

New Zealand

Phone

+64 3 470 9451

Fax

shona.neehoff@otago.ac.nz

Contact person for scientific queries

Name

Paul Glue

Address

Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054

Country

New Zealand

Phone

+64 21 243 3372

Fax

paul.glue@otago.ac.nz

No information has been provided regarding IPD availability

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.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically