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Trial registered on ANZCTR


Registration number
ACTRN12621000528853
Ethics application status
Approved
Date submitted
23/03/2021
Date registered
5/05/2021
Date last updated
5/05/2021
Date data sharing statement initially provided
5/05/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Ketamine for methamphetamine use in young people
Scientific title
MethAmphetamine use in young people: safety and tolerability of Sub-anaesthetic Ketamine, An Open-label Trial
Secondary ID [1] 303278 0
N/A
Universal Trial Number (UTN)
Trial acronym
MASKOT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Methamphetamine use problems 320474 0
Condition category
Condition code
Mental Health 318358 318358 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Low-dose ketamine, administered subcutaneously by a study clinician (medical doctor or nurse) once a week for 2 weeks. The starting dose (Level 1) of ketamine is 0.75mg/kg, followed by the second dose (0.9mg/kg; Level 2) after at least 7 days, if participants are able to tolerate the initial dose without clinically significant discomfort. Those who are unable to tolerate the starting dose (Level 1) will have their dosage reduced to 0.6mg/kg (Level 0) for the second dose administration. Medication administration and missed administration sessions will be recorded on study documentation.
Intervention code [1] 319613 0
Treatment: Drugs
Comparator / control treatment
Open label trial with no control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326365 0
Intervention safety, as indexed by change from baseline in average past month occasions of ketamine use, measured with the Timeline Follow Back
Timepoint [1] 326365 0
Baseline, Week 6 post-intervention commencement
Primary outcome [2] 326366 0
Intervention safety, as indexed by assessment of liver function via clinical blood tests
Timepoint [2] 326366 0
Week 2 post-intervention commencement
Primary outcome [3] 326367 0
Intervention tolerability, as indexed by the number of enrolled participants in the study withdrawing/being withdrawn from the study due to adverse effects of ketamine, assessed by audit of the study database.
Timepoint [3] 326367 0
Duration of the study (from first patient first visit to last patient last visit)
Secondary outcome [1] 391196 0
Change from baseline in ketamine craving measured with the Brief Substance Craving Scale - ketamine
Timepoint [1] 391196 0
Baseline, Weeks 1, 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [2] 391197 0
Change from baseline in average weekly occasions of ketamine use, measured with the Timeline Follow-Back
Timepoint [2] 391197 0
Baseline and Weeks 1, 2, 3, 4 post-intervention commencement
Secondary outcome [3] 391198 0
Adverse drug effects during/after ketamine sessions assessed using the Ketamine Side-Effects Tool
Timepoint [3] 391198 0
At five timepoints during ketamine sessions, within 48 hours after ketamine sessions, and at weeks 2, 3, 4, and 6.
Secondary outcome [4] 391199 0
Pulse change from baseline during acute ketamine administration assessed using an automated heart rate monitor
Timepoint [4] 391199 0
During ketamine sessions, before ketamine administration and at 15, 30, 60, 120, and 240 minutes post-ketamine administration
Secondary outcome [5] 391200 0
Peak abuse liability-related subjective effects of ketamine measured with the Drug Effects Questionnaire, monitored during acute ketamine administration
Timepoint [5] 391200 0
During ketamine sessions, at 15, 30, 60, 120, and 240 minutes post-ketamine administration
Secondary outcome [6] 391201 0
Peak psychotic-like drug effects during sessions measured with the Brief Psychotic Rating Scale
Timepoint [6] 391201 0
During ketamine sessions, at 60 and 120 minutes post-ketamine administration
Secondary outcome [7] 391202 0
Ability to consent 20 participants into the study, assessed by audit of study database
Timepoint [7] 391202 0
Duration of the study (from first patient first visit to last patient last visit)
Secondary outcome [8] 391203 0
Number of enrolled participants in the study completing both ketamine sessions, assessed by audit of study database
Timepoint [8] 391203 0
Duration of the study (from first patient first visit to last patient last visit)
Secondary outcome [9] 391205 0
Change in past week days of methamphetamine use from baseline measured with the Timeline Follow-Back
Timepoint [9] 391205 0
Baseline and Weeks 2, 3, 4, 6 post-intervention commencement
Secondary outcome [10] 391206 0
Change in past week methamphetamine use quantity (average use in grams per day of use); measured with the Timeline Follow-Back
Timepoint [10] 391206 0
Baseline and Weeks 2, 3, 4, 6 post-intervention commencement
Secondary outcome [11] 391207 0
Change in past week methamphetamine use from baseline measured with quantitative urine analysis
Timepoint [11] 391207 0
Baseline and Weeks 2, 3, 4, 6 post-intervention commencement
Secondary outcome [12] 391208 0
Change in methamphetamine craving from baseline measured with the Brief Substance Craving Scale - methamphetamine
Timepoint [12] 391208 0
Baseline and Weeks 2, 3, 4, 6 post-intervention commencement
Secondary outcome [13] 391209 0
Change in methamphetamine withdrawal symptoms from baseline measured with the Amphetamine Withdrawal Questionnaire
Timepoint [13] 391209 0
Baseline and Weeks 2, 3, 4, 6 post-intervention commencement
Secondary outcome [14] 391210 0
Change in methamphetamine craving within 48 hours after each of two ketamine sessions, compared with pre-ketamine administration methamphetamine craving scores, measured with the Brief Substance Craving Scale - methamphetamine
Timepoint [14] 391210 0
In each ketamine session before ketamine administration, and within 48 hours after each treatment session
Secondary outcome [15] 391214 0
Change from baseline in past week days of alcohol use, measured with Timeline Follow-back
Timepoint [15] 391214 0
Baseline and Weeks 2, 3, 4, 6 post-intervention commencement
Secondary outcome [16] 393236 0
Change from baseline in past week days of cannabis use, measured with Timeline Follow-back
Timepoint [16] 393236 0
Baseline and weeks 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [17] 393237 0
Change from baseline in past week days of GHB and/or GLB use, measured with Timeline Follow-back
Timepoint [17] 393237 0
Baseline and Weeks 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [18] 393238 0
Change from baseline in past week days of drug use other than methamphetamine, ketamine, alcohol, cannabis and GHB/GBL (e.g. cocaine, opioids, ecstasy) measured with Timeline Follow-back
Timepoint [18] 393238 0
Baseline and Weeks 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [19] 393239 0
Number of positive breath alcohol samples, assessed using a breathalyser
Timepoint [19] 393239 0
Baseline, and weeks 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [20] 393240 0
Number of urine tests positive for THC
Timepoint [20] 393240 0
Baseline and Weeks 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [21] 393241 0
Number of urine tests positive for cocaine
Timepoint [21] 393241 0
Baseline and weeks 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [22] 393242 0
Number of urine tests positive for opioids
Timepoint [22] 393242 0
Baseline and Weeks 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [23] 393243 0
Number of urine tests positive for MDMA
Timepoint [23] 393243 0
Baseline and weeks 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [24] 393244 0
Number of urine tests positive for benzodiazepines
Timepoint [24] 393244 0
Baseline and weeks 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [25] 393245 0
Change from baseline in depression symptoms, measured with the Self-Rated Quick Inventory of Depression Symptomatology
Timepoint [25] 393245 0
Baseline and weeks 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [26] 393246 0
Change from baseline in generalised anxiety symptoms, measured with the Generalised Anxiety Disorder Scale
Timepoint [26] 393246 0
Baseline and weeks 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [27] 393247 0
Change from baseline in anxiety measured with the Overall Anxiety Severity and Impairment Scale
Timepoint [27] 393247 0
Baseline and weeks 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [28] 393248 0
Change from baseline in distress, measured with the Kessler-10 Psychological Distress Scale
Timepoint [28] 393248 0
Baseline and weeks 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [29] 393249 0
Change from baseline in functioning, measured with the Social and Occupational Functioning Assessment Scale
Timepoint [29] 393249 0
Baseline and weeks 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [30] 393250 0
Change from baseline in sleep, measured with the Pittsburgh Sleep Quality Index
Timepoint [30] 393250 0
Baseline and weeks 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [31] 393251 0
Change from baseline in quality of life, measured with the Assessment of Quality of Life Scale
Timepoint [31] 393251 0
Baseline and weeks 2, 3, 4, and 6 post-intervention commencement
Secondary outcome [32] 394255 0
Blood pressure peak change from baseline during acute ketamine administration measured with a blood pressure monitor
Timepoint [32] 394255 0
During ketamine treatment sessions, before ketamine administration and at 5 time points post-ketamine administration
Secondary outcome [33] 394262 0
Peak dissociative drug effects during sessions measured with the Clinician Administered Dissociative Symptoms Scale
Timepoint [33] 394262 0
During ketamine treatment sessions, at 2 time points post-ketamine administration
Secondary outcome [34] 394263 0
Ability to complete 20 participants within the available budget and the study timeframe, assessed by audit of study database
Timepoint [34] 394263 0
Duration of the study (from first patient first visit to last patient last visit)
Secondary outcome [35] 394465 0
Methamphetamine abstinence, operationalised being abstinent from methamphetamine for at least the last 3 weeks of the study (i.e. self-report of no use of methamphetamine between weeks 3 and 6 coupled with no positive urine tests during that period; missing tests will be counted as positive);
Timepoint [35] 394465 0
Weeks 3, 4, and 6
Secondary outcome [36] 394466 0
Relapse to methamphetamine use, operationalized as 2 or more weeks of abstinence (self-report of no use of methamphetamine for at least 2 weeks coupled with no positive urine tests during that period) between weeks 1 and 4, with subsequent methamphetamine positive urine test at least once or self-report use of methamphetamine on 2 or more days within any week.
Timepoint [36] 394466 0
Weeks 1, 2, 3, 4, and 6

Eligibility
Key inclusion criteria
• 15-25 years old inclusive at consent;
• Current stimulant use disorder – methamphetamine type, moderate or severe, assessed using the Structured Clinical Interview for DSM-5;
• Current methamphetamine use, indicated by positive urine toxicology (qualitative) for methamphetamine use at either screening or baseline visits;
• Seeking treatment to reduce methamphetamine use;
• Engaged with a regular treating doctor (general practitioner or psychiatrist);
• Ability to comply with the study protocol, as determined by the CI; and
• Ability to provide informed consent (both adequate IQ and English fluency; 15 to 17 year olds will provide consent themselves, as will a parent/guardian).
Minimum age
15 Years
Maximum age
25 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• History of psychosis or bipolar disorder (other than transient drug-related symptoms) assessed with the SCID-5;
• Acute suicidality, based on clinical judgement by the study doctor or other qualified clinician, or severe depression (>15 on the Quick Inventory of Depressive Symptomatology);
• If female, pregnancy or current breastfeeding, or, if sexually active, no effective contraception;
• Abnormal liver or thyroid function as indicated by clinically significant findings on blood tests;
• If prescribed antidepressants, the participant must have been on a stable dose for >2 weeks;
• Current treatment with antipsychotic medication, mood stabiliser, or ADHD medication;
• Participation in another trial, which is likely to affect safety or data quality for this study, as determined by the CI;
• Any unstable medical or neurological condition, or medical contraindication to ketamine use, e.g. uncontrolled hypertension;
• Current or past DSM-5 diagnosis with ketamine use disorder, moderate or severe; and
• Current DSM-5 diagnosis with other substance use disorders, moderate or severe, except tobacco, caffeine, or cannabis.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
To assess change from baseline to week 6 in past month ketamine use, we will employ a repeated measures t-test. Clinically significant changes in liver function will be evaluated based on descriptive statistics. The number of participants withdrawing or being withdrawn from the study due to adverse effects of ketamine will be evaluated descriptively.

Secondary analyses: For continuous secondary outcome measures that are repeated at several time points, we will employ longitudinal linear mixed effects models or repeated-measures ANOVA. For further analyses, the number of completed ketamine administration sessions will be included as a covariate. Methamphetamine abstinence and relapse, number of participants completing both ketamine sessions, ability to consent 20 into the main treatment study, the number of positive urine and breathalyser tests across time points, and adverse side effects of ketamine administration will be assessed with descriptive statistics.

Recruitment
Recruitment status
Not yet recruiting
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)
VIC

Funding & Sponsors
Funding source category [1] 307689 0
Other Collaborative groups
Name [1] 307689 0
National Centre for Clinical Research on Emerging Drugs (NCCRED)
Address [1] 307689 0
22-32 King St, Randwick NSW 2031
Country [1] 307689 0
Australia
Primary sponsor type
Other
Name
Orygen National
Address
35 Poplar Rd (Locked Bag 10)
Parkville VIC 3052
Country
Australia
Secondary sponsor category [1] 308953 0
None
Name [1] 308953 0
Address [1] 308953 0
Country [1] 308953 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307724 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 307724 0
Office For Research
Level 2, South West
300 Grattan Street
Parkville 3055 Victoria
Ethics committee country [1] 307724 0
Australia
Date submitted for ethics approval [1] 307724 0
28/10/2020
Approval date [1] 307724 0
12/01/2021
Ethics approval number [1] 307724 0
HREC/58535/MH-2020

Summary
Brief summary
This is an open-label Phase II pilot study to investigate the safety and tolerability of two doses of ketamine in young people with stimulant use disorder, methamphetamine-type seeking treatment to reduce their methamphetamine use. The study treatments will be provided in addition to treatment-as-usual received by participants during their regular clinical care. All participants will be engaged with a GP or psychiatrist, either through headspace, Orygen, or in the community, and they will be offered referral into outpatient alcohol and other drug treatment at headspace or in the community. They will receive psychiatric and medical review by the study doctor during screening and at weeks 1 and 2. Participants will complete comprehensive screening and baseline testing. They will then undergo two ketamine administration sessions (subcutaneous; initial dose 0.75 mg/kg) separated by at least 7 days. Assessments will occur at baseline and weeks 2, 3, 4, and 6.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 108282 0
A/Prof Gillinder Bedi
Address 108282 0
35 Poplar Rd (Locked Bag 10)
Parkville VIC 3052
Country 108282 0
Australia
Phone 108282 0
+61 466 247 240
Fax 108282 0
Email 108282 0
gill.bedi@orygen.org.au
Contact person for public queries
Name 108283 0
A/Prof Gillinder Bedi
Address 108283 0
35 Poplar Rd (Locked Bag 10)
Parkville VIC 3052
Country 108283 0
Australia
Phone 108283 0
+61 466 247 240
Fax 108283 0
Email 108283 0
gill.bedi@orygen.org.au
Contact person for scientific queries
Name 108284 0
A/Prof Gillinder Bedi
Address 108284 0
35 Poplar Rd (Locked Bag 10)
Parkville VIC 3052
Country 108284 0
Australia
Phone 108284 0
+61 466 247 240
Fax 108284 0
Email 108284 0
gill.bedi@orygen.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data collected include sensitive information. For this reason, we do not have ethical approval to make IPD data available
What supporting documents are/will be available?
No other documents available
Summary results
No Results