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Trial registered on ANZCTR


Registration number
ACTRN12624001061527
Ethics application status
Approved
Date submitted
2/08/2024
Date registered
3/09/2024
Date last updated
3/09/2024
Date data sharing statement initially provided
3/09/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Oral Lisdexamfetamine for the treatment of Acute Methamphetamine withdrawal (the OLAM trial): A randomised controlled trial
Scientific title
Efficacy of Oral Lisdexamfetamine for the treatment of Acute Methamphetamine withdrawal symptoms (the OLAM trial): A randomised controlled trial
Secondary ID [1] 312630 0
None
Universal Trial Number (UTN)
U1111-1311-5066
Trial acronym
OLAM
Linked study record
This study is informed by the pilot trial of oral lisdexamfetamine for the treatment of acute methamphetamine withdrawal (ACTRN12621000045819)

Health condition
Health condition(s) or problem(s) studied:
Acute methamphetamine withdrawal 334585 0
Condition category
Condition code
Mental Health 331180 331180 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Lisdexamfetamine dimesylate 250mg, oral once daily, reducing over 7 days plus standard of care withdrawal management. Participants will be blinded to the taper in this trial, Participants in the active group will recieve 250mg lisdexamfetamine on Day 1, reducing my 50mg per day followed by a 2 day placebo washout. Participants will recieve 5 capsules per day of 50mg lisdexamfetamine (and from Day 2) placebo to make up the daily dose, all at once each morning
This will occure during inpatient admission for acute methamphetamine withdrawal, and the medication will be administered by registered nurses
Adherence will be monitored by nursing supervised dosing as per standard procedures for all schedule 8 medications, and recorded in the schedule 8 log and the participant's individual medical records.
Placebo capsules will be manufactured to be indistinguashable from active medication, and will be comprised of a gelatine capsule and microcrystaline cellulose filling. Placebo capsules will be administered along side active capsules to blind taper of the active medication
All participants will recieve standard of care psychosocial support during the 7-day inpatient period in line with each site's current clinical practice, comprising of psychosocial care (i.e. groups, psychoeducation etc offered daily) and/or case management. This will be monitored via self report and audit of medical records
Intervention code [1] 329149 0
Treatment: Drugs
Comparator / control treatment
Matched placebo; plus standard of care withdrawal maangement. Participants will recieve 5 capsules of matched placebo per day over 7 days administered all at once in the morning
Placebo capsules will be manufactured to be indistinguashable from active medication, and will be comprised of a gelatine capsule and microcrystaline cellulose filling.
All participants will recieve standard of care psychosocial support during the 7-day inpatient period in line with each site's current clinical practice, comprising of psychosocial care (i.e. groups, psychoeducation etc offered daily) and/or case management. This will be monitored via self report and audit of medical records
Control group
Placebo

Outcomes
Primary outcome [1] 338942 0
To determine the effectiveness of a tapering dose regimen of lisdexamfetamine to ameliorate the symptoms of acute methamphetamine withdrawal over 7 days
Timepoint [1] 338942 0
Days 0 (baseline), 1, 2, 3, 4, 5, 6, 7 (primary timepoint) post-baseline
Secondary outcome [1] 437969 0
Retention in treatment
Timepoint [1] 437969 0
Upon conclusion of the study
Secondary outcome [2] 437970 0
Treatment satisfaction
Timepoint [2] 437970 0
Days 5 and 7 post baseline
Secondary outcome [3] 437971 0
Sleep quality and duration
Timepoint [3] 437971 0
Days 1, 2, 3, 4, 5, 6, 7 post-baseline
Secondary outcome [4] 437972 0
Anxiolytic / sedative medication utilisation for symptom management
Timepoint [4] 437972 0
Days 1, 2, 3, 4, 5, 6, 7 post baseline
Secondary outcome [5] 437973 0
Safety
Timepoint [5] 437973 0
Up to Day 28 post baseline
Secondary outcome [6] 437974 0
Post-intervention withdrawal symptoms
Timepoint [6] 437974 0
Days 14, 21, 28 post baseline
Secondary outcome [7] 437975 0
Methamphetamine use
Timepoint [7] 437975 0
Days 14, 21, 28, 56, 84 post baseline
Secondary outcome [8] 437976 0
Depression and anxiety
Timepoint [8] 437976 0
Days 7, 14, 21, 28, 56, 84 post baseline
Secondary outcome [9] 437977 0
Post-withdrawal care
Timepoint [9] 437977 0
Days 14, 21, 28, 56, 84 post baseline
Secondary outcome [10] 437978 0
Cost Effectiveness: Quality adjusted life years (QALYs) and incremental cost effectiveness ratio (ICER)
Timepoint [10] 437978 0
Up to Day 28 post baseline
Secondary outcome [11] 438754 0
Anti-psychotic medication utilisation for symptom management
Timepoint [11] 438754 0
Days 1, 2, 3, 4, 5, 6, 7 post baseline
Secondary outcome [12] 438755 0
Physical and social health
Timepoint [12] 438755 0
Days 7, 14, 21, 28, 56, 84 post baseline
Secondary outcome [13] 438756 0
Post-withdrawal medication use
Timepoint [13] 438756 0
Days 14, 21, 28, 56, 84 post baseline

Eligibility
Key inclusion criteria
• Aged 18 years and older
• Presenting to drug treatment service seeking methamphetamine withdrawal treatment
• Determined by an Addiction Medicine Specialist or Psychiatrist to have methamphetamine use disorder (DSM-5-TR criteria)
• Reporting last use of methamphetamine within 72 hours of first dose of study drug
• Point-of-care urine drug test positive for methamphetamine
• Willing and able to provide written, informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Concurrent dependence on non-prescribed opioids or benzodiazepines, or alcohol or gamma-hydroxybutyrate (GHB) (based on DSM-5TR criteria)
• Lactating, pregnant or of childbearing potential and not willing to avoid becoming pregnant during the study
• Contraindications to lisdexamfetamine (per product label) other than drug dependence:
• Acute severe mental/physical comorbidity that would interfere with study participation, as assessed by the site PI
• Currently experiencing psychosis or suicidality
• Exposure to lisdexamfetamine, dexamphetamine, modafinil or methylphenidate in the 4 weeks prior to screening

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)
Randomisation will be based on a study ID allocated to each participant after they have been confirmed eligible. Trial medication will be dispensed and allocated according to the study ID contained in the randomisation schedule, which will be generated by an independent statistician and held by the trial site pharmacy.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised in a 1:1 ratio between groups using variable block randomisation (to help maintain allocation concealment), stratified by site. Electronic randomisation procedures will be conducted by study staff on a REDCap interactive web response system.
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 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
A statistical analysis plan will be developed and overseen by staff at the University of New South Wales conducting analysis (providing externally contracted statistical support). All outcome variables will be analysed on intention-to-treat principles, and missing data imputed using multiple imputation. A likelihood-based mixed model repeated measures approach will be used to analyse the primary efficacy measure of between-group difference in average AWQ score over 7 days from Baseline. Survival analysis using Cox proportional hazards regression will compare retention in protocol by adherence to study drug (to Day 5), and inpatient treatment (to Day 7) between study arms, adjusting for potential predictors (e.g., age, baseline frequency of methamphetamine use). For categorical measures such as the presence of adverse events, differences in rates between groups will be analysed using logistic regression.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
14/10/2024
Actual
Date of last participant enrolment
Anticipated
30/09/2026
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
184
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 26868 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 42930 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 317065 0
Government body
Name [1] 317065 0
NHMRC
Country [1] 317065 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital Sydney
Address
Country
Australia
Secondary sponsor category [1] 319314 0
None
Name [1] 319314 0
None
Address [1] 319314 0
Country [1] 319314 0
Other collaborator category [1] 283122 0
University
Name [1] 283122 0
University of New South Wales
Address [1] 283122 0
Country [1] 283122 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315813 0
St Vincent’s Hospital Human Research Ethics Committee
Ethics committee address [1] 315813 0
https://svhs.org.au/home/research-education/research-office
Ethics committee country [1] 315813 0
Australia
Date submitted for ethics approval [1] 315813 0
22/04/2024
Approval date [1] 315813 0
15/05/2024
Ethics approval number [1] 315813 0
2024/ETH00788

Summary
Brief summary
Untreated methamphetamine withdrawal is a significant barrier to people meeting their treatment goals. Lisdexamfetamine has the potential to help manage withdrawal from methamphetamine. This study is a randomised controlled trial of a tapering dose of lisdexamfetamine for the treatment of acute methamphetamine withdrawal, over a 7 day period in hospital. We will then follow up participants for 84 days.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 135886 0
Prof Nadine Ezard
Address 135886 0
St Vincent's Hospital Sydney, 390 Victoria St Darlinghurst NSW 2010
Country 135886 0
Australia
Phone 135886 0
+61 2 83821012
Fax 135886 0
Email 135886 0
[email protected]
Contact person for public queries
Name 135887 0
Dr Liam Acheson
Address 135887 0
St Vincent's Hospital Sydney 390 Victoria St Darlinghurst NSW 2010
Country 135887 0
Australia
Phone 135887 0
+61 2 90657809
Fax 135887 0
Email 135887 0
[email protected]
Contact person for scientific queries
Name 135888 0
Nadine Ezard
Address 135888 0
St Vincent's Hospital Sydney, 390 Victoria St Darlinghurst NSW 2010
Country 135888 0
Australia
Phone 135888 0
+61 2 83821012
Fax 135888 0
Email 135888 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Demographic and trial outcome data in a non-identifiable manner
When will data be available (start and end dates)?
Immediately following publication of results - no end date determined
Available to whom?
Due to the sensitive nature of the sample, data will be made avaliable on a case by case basis as determined by the principal investigator
Available for what types of analyses?
Only to achieve aims in the primary proposal
How or where can data be obtained?
Subject to approval from the principal investigator ([email protected])


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.