Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000311156
Ethics application status
Approved
Date submitted
6/02/2019
Date registered
28/02/2019
Date last updated
7/07/2021
Date data sharing statement initially provided
28/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Ketamine and Internalizing Disorders
Scientific title
Ketamine Therapy For Internalizing Disorders: Is There A Single Mechanism?
Secondary ID [1] 297321 0
None
Universal Trial Number (UTN)
Trial acronym
KIDs
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Depression 311429 0
Post-Traumatic Stress Disorder 311430 0
Obsessive-Compulsive Disorder 311431 0
Phobic Disorders 311432 0
Condition category
Condition code
Mental Health 310069 310069 0 0
Depression
Mental Health 310070 310070 0 0
Anxiety
Mental Health 310071 310071 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There are 4 groups; treatment-resistant MDE, OCD, PTSD, phobic states.

Each participant will receive a single dose of each of these treatments plus a psychoactive control, with a washout of at least 7 days between treatments:
Ketamine 0.5mg/kg intramuscular injection, single dose
Ketamine 1mg/kg intramuscular injection, single dose
Intervention code [1] 313575 0
Treatment: Drugs
Comparator / control treatment
Fentanyl 50mcg intramuscular injection, single dose (psychoactive control)
Control group
Active

Outcomes
Primary outcome [1] 318964 0
10 minute relaxation 16 lead EEG
Timepoint [1] 318964 0
2h after each dose
Primary outcome [2] 318965 0
Clinician-Administered PTSD Scale-5
Timepoint [2] 318965 0
24h after each dose
Primary outcome [3] 318966 0
Yale-Brown Obsessive-Compulsive Scale
Timepoint [3] 318966 0
24h after each dose
Secondary outcome [1] 366551 0
Montgomery Asberg Depression Rating Scale
Timepoint [1] 366551 0
24h after each dose
Secondary outcome [2] 366552 0
Fear Questionnaire Item 18
Timepoint [2] 366552 0
24h after each dose
Secondary outcome [3] 366553 0
Clinician Administered Dissociative States Scale
Timepoint [3] 366553 0
30 minutes after each dose
Secondary outcome [4] 366554 0
Bladder pain/interstitial cystitis symptom scale
Timepoint [4] 366554 0
Weekly for 3 weeks

Eligibility
Key inclusion criteria
• Capable of understanding and signing an informed consent
• diagnosed with one of the following DSM-5 diagnoses:
-post-traumatic stress disorder (PTSD) with a CAPS score >60;
-obsessive-compulsive disorder (OCD) with a YBOCS score >26;
-major depressive disorder (MDD) with a MADRS score >20;
-phobic state with FQ18 score >6
• Patients with PTSD, OCD or phobic state must not have MADRS scores >20 at screening.
• Patients must have had an inadequate response to prior treatment i.e. have not responded to at least two adequate trials of relevant medication and at least one trial of relevant psychotherapy.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• evidence of severe acute or chronic medical disorders,
• past or current diagnoses of schizophrenia, bipolar disorder, or current psychotic symptoms
• female patients who are pregnant or lactating
• drug use or dependence in the last 6 months
• current significant suicidal ideation
• 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)
Central randomization
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated random code
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
Crossover
Other design features
4 diagnostic groups.
For each group, treatments will be administered as a 3 way single dose crossover using balanced randomization. Each dose is separated by 1 week
Phase
Phase 1 / Phase 2
Type of endpoint/s
Pharmacodynamics
Statistical methods / analysis
Correlations and univariate analyses will be perfomed for ketamine and norketamine plasma concentrations and mood rating scores and EEG changes in an exploratory data analysis. Further analyses using pharmacokinetic, pharmacodynamic (PKPD) modelling effects will be conducted to investigate relationships between ketamine exposure (plasma concentrations) and pharmacological effects (mood scores and EEG changes).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
29/04/2019
Actual
2/11/2020
Date of last participant enrolment
Anticipated
31/05/2023
Actual
Date of last data collection
Anticipated
30/06/2023
Actual
Sample size
Target
48
Accrual to date
14
Final
Recruitment outside Australia
Country [1] 21258 0
New Zealand
State/province [1] 21258 0
Otago, Canterbury

Funding & Sponsors
Funding source category [1] 301889 0
Charities/Societies/Foundations
Name [1] 301889 0
Otago Medical Research Foundation
Country [1] 301889 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
PO Box 56
Dunedin 9054, NZ
Country
New Zealand
Secondary sponsor category [1] 301640 0
None
Name [1] 301640 0
Address [1] 301640 0
Country [1] 301640 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302578 0
Central HDEC
Ethics committee address [1] 302578 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140, NZ
Ethics committee country [1] 302578 0
New Zealand
Date submitted for ethics approval [1] 302578 0
20/02/2019
Approval date [1] 302578 0
08/07/2020
Ethics approval number [1] 302578 0
19/CEN/21

Summary
Brief summary
Internalizing disorders, characterized by quiet, internal distress, include DSM5 diagnoses such as Generalized Anxiety Disorder, Social Anxiety Disorder, Major Depressive Disorder, Panic Disorder, Post-Traumatic Stress Disorder, Obsessive Compulsive Disorder and phobic states.

In contrast to slow and variable responsiveness to conventional medications, ketamine is rapidly effective in all internalizing disorders assessed so far. To account for these differences in speed of onset and breadth of activity between conventional treatments and ketamine, we have recently proposed a ‘double hit’ model for internalizing disorders, with 2 distinct forms of neural dysfunction to coincide. One hit, which is sensitive to ketamine, is disorder general: dysfunction of a neural system linked to high levels of the personality trait of neuroticism. The other hit is disorder-specific: dysfunction of one of a set of disorder-specific neural modules (already identified by theory), each with its own particular pattern of sensitivity to conventional drugs.

We predict that ketamine will produce similar right frontal EEG changes that will correlate with symptom improvement across all of these internalizing disorders. These findings will potentially provide clinicians and researchers with results that could produce major theoretical advances (e.g. for reclassification of anxiety and depressive disorders) and may support wider use of ketamine as a treatment for internalizing disorders.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes
N/A

Contacts
Principal investigator
Name 90706 0
Prof Paul Glue
Address 90706 0
Dunedin School of Medicine, PO Box 56, Dunedin 9054
Country 90706 0
New Zealand
Phone 90706 0
+64 3 479 7272
Fax 90706 0
Email 90706 0
[email protected]
Contact person for public queries
Name 90707 0
Prof Paul Glue
Address 90707 0
Dunedin School of Medicine, PO Box 56, Dunedin, 9054
Country 90707 0
New Zealand
Phone 90707 0
+64 3 479 7272
Fax 90707 0
Email 90707 0
[email protected]
Contact person for scientific queries
Name 90708 0
Dr Shabah Shadli
Address 90708 0
Department of Psychology
University of Otago
PO Box 56
Dunedin 9054
Country 90708 0
New Zealand
Phone 90708 0
+64 3 479 7644
Fax 90708 0
Email 90708 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Need to discuss with co-investigators


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.