Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000562875
Ethics application status
Approved
Date submitted
3/03/2021
Date registered
12/05/2021
Date last updated
27/05/2024
Date data sharing statement initially provided
12/05/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
An open-label feasibility study of ketamine-assisted therapy.
Scientific title
An open-label feasibility study of ketamine-assisted therapy in adults with treatment-resistant depression.
Secondary ID [1] 303577 0
None
Universal Trial Number (UTN)
U1111-1259-0551
Trial acronym
KETIMDEP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
treatment-resistant depression 320954 0
Condition category
Condition code
Mental Health 318767 318767 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study intervention will be psychotherapy in combination with the administration of ketamine. The participant will have a psychotherapy preparation session before the day of their first ketamine administration. Ketamine will be administered by a research team clinician intramuscular injection. The first dose will be 0.5mg/kg for participants between 50-100kg, followed by an optional second dose of 20-40mg, 12 minutes later. The dose on the first ketamine session will be 0.3mg/kg for participants over 100kg, followed by an optional second dose of 20-40mg, 12 minutes later.
The dose on the second ketamine session will be 0.5-0.75mg/kg for participants between 50-100kg, followed by an optional second dose of 20-40mg, 12 minutes later. The first dose will be 0.3-0.5mg/kg for participants over 100kg, followed by an optional second dose of 20-40mg, 12 minutes later.
The dose on the third ketamine session will be 0.5-0.75mg/kg for participants between 50-100kg, followed by an optional second dose of 20-40mg, 12 minutes later. The first dose will be 0.3-0.5mg/kg for participants over 100kg, followed by an optional second dose of 20-40mg, 12 minutes later.
The ketamine sessions will occur once a week, in three consecutive weeks.
The participant will have an integration psychotherapy session within 2 days after each ketamine session. The ketamine injection will be administered by a study team member (research nurse or research physician). Adherence to the intervention will be monitored using session-specific checklists entered into the Redcap data management system (https://redcap.fmhs.auckland.ac.nz/). Regarding the psychotherapy sessions; the preparation session and the integration sessions will each be for two hours. The therapy will be provided by a registered clinician (psychiatrist, psychologist, or psychotherapist) with extensive psychotherapy training. The therapy sessions will occur at the University of Auckland Clinical Research Centre. The preparation session will include the following components: orientation to the treatment facility, providing information about the treatment including regarding the ketamine experience and the subsequent possible responses and discussion about the integration session; establishment of a therapeutic alliance, gathering of information including participant's intentions and expectations, as well as cultural background and beliefs; exploration of mechanisms to ensure the safety of participant including boundaries and preferences regarding touch.
On the study day, the therapist will be present during the treatment with ketamine and for several hours afterward to provide psychological support for the participant. On that day, the participant can share his/her experience if so inclined.
The integration sessions will include the facilitation of emotional processing of the ketamine experience, identify and explore any difficulties that arose from the experience, supporting the participant in identifying and making meaning from experiences and support the process of healing and growth. The therapist will also encourage the participant to develop or maintain healthy supportive relationships and restorative self-care routines.
Intervention code [1] 319873 0
Treatment: Drugs
Intervention code [2] 319874 0
Treatment: Other
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326710 0
The degree of response to the intervention based on the change in the severity of the depressive episode will be assessed using the Montgomery-Asberg Depression Rating Scale (MADRS)
Timepoint [1] 326710 0
Day 7 post final ketamine administration.
Secondary outcome [1] 392440 0
The degree of response to the intervention based on the change in the severity of the depressive episode will be assessed using the Montgomery-Asberg Depression Rating Scale (MADRS)
Timepoint [1] 392440 0
1 day post each administration of ketamine, 1 week, 1 month, 3 months, and 6 months following the final ketamine administration.
Secondary outcome [2] 392441 0
The degree of response to the intervention based on change in severity of the anxiety symptoms as assessed by the Hamilton Anxiety Rating Scale.
Timepoint [2] 392441 0
4 hours post administration of ketamine, 1 day post administration of ketamine, 7 day post administration of ketamine, and day 28 post administration of ketamine
Secondary outcome [3] 392442 0
The degree of response to the intervention based on the change in the severity of the depressive episode will be assessed by the Quick Inventory of Depressive Symptomatology (QIDS)
Timepoint [3] 392442 0
1 day post each administration of ketamine, 1 week, 1 month, 3 months, and 6 months following the final ketamine administration.
Secondary outcome [4] 392443 0
Measurement of altered states of consciousness will be assessed using the 5 Dimensional Altered States of Consciousness Rating Scale (5D-ASC)
Timepoint [4] 392443 0
4 hours post each administration of ketamine.
Secondary outcome [5] 392444 0
Personality trait changes will be assessed using the Big Five Inventory (BFI-2)
Timepoint [5] 392444 0
Day 28 post final administration of ketamine.
Secondary outcome [6] 392445 0
Mental wellness will be assessed using the HERO Wellness Scale
Timepoint [6] 392445 0
4 hours and 1 day post each administration of ketamine, 1 week, 1 month, 3 months, and 6 months following the final ketamine administration.
Secondary outcome [7] 394073 0
The degree of absorption will be measured by the Modified Tellegen Absorption Scale (MODTAS)
Timepoint [7] 394073 0
4 hours post each administration of ketamine.
Secondary outcome [8] 394074 0
Distressing and challenging experiences will be measured using the Challenging Experience Questionnaire (CEQ)
Timepoint [8] 394074 0
4 hours and 1 day post each administration of ketamine, 1 week, 1 month, 3 months, and 6 months following the final ketamine administration.
Secondary outcome [9] 394075 0
Tolerability of viewing the time-variable fractal images or time-variable checkerboard images will be assessed using a Likert Tolerability scale
Timepoint [9] 394075 0
4 hours post each administration of ketamine.
Secondary outcome [10] 394076 0
The participant's expectancy of the treatment will be assessed using the Credibility and Expectancy Questionnaire (CAEQ)
Timepoint [10] 394076 0
4 hours post each administration of ketamine, and 1 day post each administration of ketamine.
Secondary outcome [11] 394077 0
The quality of the therapeutic alliance and engagement with therapist will be assessed using a modified version of the Session Rating Scale (SRS)
Timepoint [11] 394077 0
4 hours and 1 day post each administration of ketamine, 1 week, 1 month, 3 months, and 6 months following the final ketamine administration.
Secondary outcome [12] 394078 0
Recruitment rate will be measured from audit of study records.
Timepoint [12] 394078 0
Every six months and at conclusion of study.
Secondary outcome [13] 395411 0
Ethnicity of possible participants referred based on New Zealand census ethnic group dataset will be measured from audit of study records.
Timepoint [13] 395411 0
Every six months and at conclusion of study.
Secondary outcome [14] 395412 0
Ethnicity of possible participants screened based on New Zealand census ethnic group dataset will be measured from audit of study records
Timepoint [14] 395412 0
Every six months and at conclusion of study.
Secondary outcome [15] 395413 0
Ethnicity of participants enrolled based on New Zealand census ethnic group dataset will be measured from audit of study records.
Timepoint [15] 395413 0
Every six months and at conclusion of study.
Secondary outcome [16] 395414 0
Ethnicity of participants completing study based on New Zealand census ethnic group dataset will be measured from audit of study records.
Timepoint [16] 395414 0
Every six months and at conclusion of study.

Eligibility
Key inclusion criteria
Adult patients who meet DSM-5 criteria for Major Depressive Disorder or Bipolar Disorder and:
1) will and able to give informed consent for participation in the study
2) Male or female, aged 18 years or above and less than age 70.
3) If Bipolar Disorder must be on a mood stabilizing medication for the duration of the study
4) current depressive episode for at least three months
5) MADRS > or = 20
6) Inadequate response to at least two antidepressant treatments one of which can include the current episode.
7) must be stable on any psychotropic medication for at least four weeks prior to the study day.
Minimum age
18 Years
Maximum age
69 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participant may not enter the trial if ANY of the following apply:
• Female participant who is pregnant, lactating or planning pregnancy during the course of the trial.
• Significant renal or hepatic impairment.
• Cardiovascular conditions including severe cardiovascular disease, heart failure, severe or poorly controlled hypertension, recent myocardial infarction, history of stroke, cerebral trauma, or intracerebral mass or haemorrhage.
• Abnormal heart rate or blood pressure checked at screening.
• Participants who have participated in another research trial involving an investigational product in the past 12 weeks.
• History of significant psychotic episode(s).
• Any unstable medical or neurologic condition.
• Planned major changes to psychotropic medication.
• Imminent risk of suicide as determined by the CSSRS and MADRS/clinical interview.
• Planned or probable use of ECT.
• Active substance use disorder in the previous 6 months.
• Regular use of any medication deemed to be contraindicating as judged by the attending study physicians
• Inability to speak or read English.
• Any history of abuse of ketamine or phencyclidine.
• Contraindication to the use of ketamine according to manufacturer guidelines including hypersensitivity to the drug or its components.
• Planned use of ketamine, for example, for pain control.
• Unable to fast for four hours prior to administration of ketamine.
• 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 the following medications:memantine / amantadine / rimantadine / dextromethorphan/procyclidine/ lamotrigine.

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)
NA.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
NA
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Description of Statistical Methods

Given the design of the trial, the primary statistic of interest for this trial will be the magnitude of change in MADRS score from baseline. This will be calculated as both a percentage change and Cohen’s d value (with corresponding 95% confidence intervals and p values) using MADRS scores measured at baseline and each time-point. Responder rate, defined as the percentage of participants who achieve a 50% or greater reduction in MADRS score will also be calculated at each time-point.
In terms of feasibility assessment, quality of outcome data collection (dropouts, missing data) will be presented using summary statistics, with frequencies and percentages for categorical variables and means with appropriate measures of spread for continuous variables. Dropouts will be categorised by the investigators as Missing at Random (MAR) or Missing Not at Random (MNAR).

Power Calculations

Given the open-label nature of the trial comparisons can only be made against baseline. Nevertheless for completeness the following power calculations were performed in G*Power 3.1 [52]. With a sample size of 30, a significance level of a = 0.05, (1-ß) = 0.8 we are powered to see effect sizes of 0.93. Effect sizes reported for ketamine in the literature are typically ~ 1. Any effect size obtained > 0.5 might be considered promising and worthy of future investigation. In terms of correlations of outcome measures with baseline characteristics we are powered to see correlations where r>0.42 (a = 0.05, (1-ß) = 0.8).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/06/2022
Actual
8/08/2022
Date of last participant enrolment
Anticipated
28/11/2025
Actual
Date of last data collection
Anticipated
29/05/2026
Actual
Sample size
Target
30
Accrual to date
12
Final
Recruitment outside Australia
Country [1] 23496 0
New Zealand
State/province [1] 23496 0
Auckland Region

Funding & Sponsors
Funding source category [1] 307998 0
Charities/Societies/Foundations
Name [1] 307998 0
The Oakley Mental Health Foundation
Country [1] 307998 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
University of Auckland
Department of Psychological Medicine
School of Medicine
Building 507
Level 3
22-30 Park Ave
Grafton
Auckland 1023
Country
New Zealand
Secondary sponsor category [1] 308720 0
None
Name [1] 308720 0
Address [1] 308720 0
Country [1] 308720 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307992 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 307992 0
Ethics committee country [1] 307992 0
New Zealand
Date submitted for ethics approval [1] 307992 0
27/01/2021
Approval date [1] 307992 0
29/03/2021
Ethics approval number [1] 307992 0

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

Contacts
Principal investigator
Name 109158 0
Dr Nicholas Hoeh
Address 109158 0
Dept of Psychological Medicine
School of Medicine
Building 507
Level 3
22-30 Park Avenue
Grafton
Auckland 1023
Country 109158 0
New Zealand
Phone 109158 0
+64 9 923 7703
Fax 109158 0
Email 109158 0
n.hoeh@auckland.ac.nz
Contact person for public queries
Name 109159 0
Nicholas Hoeh
Address 109159 0
Dept of Psychological Medicine
School of Medicine
Building 507
Level 3
22-30 Park Avenue
Grafton
Auckland 1023
Country 109159 0
New Zealand
Phone 109159 0
+64 9 923 7703
Fax 109159 0
Email 109159 0
n.hoeh@auckland.ac.nz
Contact person for scientific queries
Name 109160 0
Nicholas Hoeh
Address 109160 0
Dept of Psychological Medicine
School of Medicine
Building 507
Level 3
22-30 Park Avenue
Grafton
Auckland 1023
Country 109160 0
New Zealand
Phone 109160 0
+64 9 923 7703
Fax 109160 0
Email 109160 0
n.hoeh@auckland.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
Given small number of participants from a vulnerable population IPD will not be available.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
10864Study protocol  n.hoeh@auckland.ac.nz 381525-(Uploaded-18-04-2022-09-14-51)-Study-related document.docx
10865Informed consent form  n.hoeh@auckland.ac.nz 381525-(Uploaded-17-02-2022-09-46-54)-Study-related document.docx
10866Ethical approval  n.hoeh@auckland.ac.nz 381525-(Uploaded-14-04-2021-15-28-41)-Study-related document.pdf
15839Ethical approval    381525-(Uploaded-17-02-2022-09-46-54)-Study-related document.pdf



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.