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
ACTRN12616001614482
Ethics application status
Approved
Date submitted
8/06/2016
Date registered
22/11/2016
Date last updated
27/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of baclofen on methamphetamine dependent subjects.
Scientific title
The effect of baclofen vs placebo on the activation of the mesolimbic dopaminergic system in methamphetamine dependent subjects: fMRI study.
Secondary ID [1] 290576 0
None
Universal Trial Number (UTN)
U1111-1184-0481
Trial acronym
BACMETA-001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Methamphetamine Addiction 299069 0
Condition category
Condition code
Mental Health 299105 299105 0 0
Addiction
Neurological 299157 299157 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Titration of baclofen or placebo in 18 methamphetamine dependent subjects to a dose of oral baclofen 60mg/day (vs placebo) in a closed clinical trials unit over 6 days . The stepped dosage regime shown in Control/comparator (ANZCTR) field is required because baclofen side effects occur when the dose increase is too rapid.
Day1 (total= 5mg): Breakfast (no dose), Lunch (no dose), Dinner (5mg),
Day2 (total= 15mg): Breakfast (5mg), Lunch (5mg), Dinner (5mg),
Day3 (total= 25mg): Breakfast (5mg), Lunch (10mg), Dinner (10mg),
Day4 (total= 35mg): Breakfast (10mg), Lunch (10mg), Dinner (15mg),
Day5 (total= 50mg): Breakfast (15mg), Lunch (15mg), Dinner (20mg),
Day6 (total= 60mg): Breakfast (20mg), Lunch (20mg), Dinner (20mg)
Each dose of medication, baclofen or placebo, will be administered by study staff from the subject's individual blister pack of study medication.
The measurement of effect was fMRI evaluation of activation of the mesolimbic dopaminergic system in response to subliminal visual drug cues.
Intervention code [1] 294986 0
Treatment: Drugs
Comparator / control treatment
The study is placebo controlled. A compounding pharmacy will produce visually identical tablets of both placebo (microcellulose) and baclofen which will be packaged in blister packs for the 7 day period in the clinical trails unit. Each patient will receive tablets from a blister pack (of either baclofen or placebo) which will be assigned in the randomisation schedule. The subjects will otherwise receive the same regime and fMRI scans.
Control group
Placebo

Outcomes
Primary outcome [1] 298573 0
The difference in activation of the mesolimbic dopaminergic system in response to methamphetamine drug cues in methamphetamine dependent patients will be measured by fMRI scanning.
Timepoint [1] 298573 0
Measured at day 7 of treatment with baclofen or placebo
Secondary outcome [1] 324613 0
Differences in methamphetamine cravings assessed on daily assessment on a 1-10 scale between the baclofen vs placebo groups.
Timepoint [1] 324613 0
Measured daily in the first 7 days (while in the clinical trials unit) and at 5 weeks from commencement of baclofen or placebo.
Secondary outcome [2] 324614 0
The difference in methamphetamine use between patients on baclofen vs no medication measured by per self reported use and urine drug screening .
Timepoint [2] 324614 0
Measured at 3, 6, 9 and 12 months post commencement of the trial.

Eligibility
Key inclusion criteria
1. Methamphetamine Dependent individuals (DSM criteria).
2. Aged 18 - 40 years.
3. Using methamphetamine intravenously or by smoking.
4. Using methamphetamine at least 8 out of previous 30 days prior to the screening interview.
5. Available and willing to undertake a 7 day inpatient detoxification in a closed clinical trial unit.
6. Able to undergo fMRI – no claustrophobia, no implanted metal etc.
7. Competent and willing to consent via written informed consent to participate in the trial including drug testing, screening tests and follow up.
Minimum age
18 Years
Maximum age
40 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Taking oral dopaminergic medication in the last 8 weeks – especially antipsychotic medications.
2. Any use of depot antipsychotic medication.
3. History of psychosis, seizures or organic brain syndrome.
4. Physically dependent on alcohol, cannabis or benzodiazepines (DSM Criteria).
5. Clinically significant medical conditions that, in the opinion of the investigator, may adversely impact on the participant’s ability to complete the study, including, but not limited to - Cardiovascular, Haematological, Hepatic, Renal, Neurological, Endocrine.
6. Known HIV infection or has a positive test for human immunodeficiency virus (HIV) at the screening visit.
7. History of brain trauma.
8. History of violent behaviour, antisocial or borderline personality disorder.
9. Homeless.
10. Any other condition which, in the opinion of the Investigator, makes the volunteer unsuitable for the study.
11. Unwillingness or inability to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the participant returning for follow-up visits on schedule.

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)
Webster packed medication in random sequence active vs placebo
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated
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 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The sample size was determined by the maximum number of subjects which the study grant would fund which was 18 subjects. The study is a replica of a study of 20 cocaine dependent subjects but with only a single fMRI so comparisons were inter- subject ie purely baclofen vs placebo.. In this study, the comparisons will be inter- and intra-subject as each subject will have 2 fMRIs, the first prior to administration of the trial medication and the second at the end of titration of the trial medication.
Functional MRI data analysis will be carried out using SPM8 software (Wellcome Department of Cognitive Neurology, London).

Recruitment
Recruitment status
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)
WA

Funding & Sponsors
Funding source category [1] 293777 0
Government body
Name [1] 293777 0
SHRAC Reseach Translation Project 2015 Grant
Address [1] 293777 0
WA Department of Health
189 Royal Street East Perth 6004
Western Australia
Country [1] 293777 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Linear Clinical Research Ltd
Address
1st Floor B Block
Hospital Avenue
Nedlands, WA, 6009
Country
Australia
Secondary sponsor category [1] 292605 0
None
Name [1] 292605 0
Address [1] 292605 0
Country [1] 292605 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295216 0
Bellbery Limited
Ethics committee address [1] 295216 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [1] 295216 0
Australia
Date submitted for ethics approval [1] 295216 0
10/10/2016
Approval date [1] 295216 0
02/03/2017
Ethics approval number [1] 295216 0
2016-07-594

Summary
Brief summary
Methamphetamine addiction is a major and growing problem in Australia, with a considerable individual, family and community burden. The current trend is a rapid increase in the use of crystal methamphetamine, the most addictive form, from 10% of users in 2010 to over 50% in 2014. Current treatment options for methamphetamine addiction are all based on Cognitive Behavioural Therapy (CBT) and have very low rates of durable abstinence. There are no proven pharmacotherapy options to assist in attaining and maintaining abstinence. The rapid increase in the use of high purity, highly addictive forms of methamphetamine, coupled with a lack of effective treatment, portends a public health catastrophe in Australia as outlined in the National Ice Action Strategy announced in April 2015.
The key focus of treatment is to stop addicted individuals succumbing to the intense drug cravings on exposure to “drug cues”: anything that evokes drug memories eg places or people associated with their methamphetamine use. The treatments based on CBT aim to alter the individual’s response to drug cues but the igniting of these intense cravings is outside of conscious control. A more effective treatment strategy is to weaken the intensity of drug cravings with anti-craving medication.
Baclofen is a strong candidate for methamphetamine addiction treatment due to its proven effectiveness in suppressing drug cravings for cocaine, another stimulant drug which, like
methamphetamine, acts via the dopamine reward pathways of the brain.
A 2014 study on cocaine addiction used functional MRI (fMRI) to objectively study the brain activation patterns in cocaine addicts in response to cocaine associated images (drug cues). The subjects treated with baclofen showed a dramatic and specific suppression of activation of the brain’s reward pathways compared to the placebo group. This provides a mechanistic explanation for the clinical effectiveness of baclofen in suppressing cravings for and the use of cocaine in addicted individuals.
The study proposed in this application will reproduce the fMRI/cocaine study in 18 methamphetamine addicted subjects to test the effectiveness of baclofen (vs placebo) in
suppressing reward pathway activation in response to methamphetamine drug cues. If baclofen is effective, it would provide the foundation for clinical trials of baclofen therapy
combined with standard CBT treatment for methamphetamine addiction.
This study seeks to rapidly establish if baclofen has an anti-craving action in the methamphetamine addicted brain. A positive result will accelerate baclofen treatment being
adopted into current treatment programs for methamphetamine addiction with the aim of increasing durable abstinence rates.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66546 0
Dr Amanda Stafford
Address 66546 0
Emergency Department
Royal Perth Hospital
Wellington Street
Perth 6000
Western Australia
Country 66546 0
Australia
Phone 66546 0
+618 92241741
Fax 66546 0
+618 92247045
Email 66546 0
amanda.stafford@health.wa.gov.au
Contact person for public queries
Name 66547 0
Dr Amanda Stafford
Address 66547 0
Emergency Department
Royal Perth Hospital
Wellington Street
Perth 6000
Western Australia
Country 66547 0
Australia
Phone 66547 0
+618 92241741
Fax 66547 0
+618 92247045
Email 66547 0
amanda.stafford@health.wa.gov.au
Contact person for scientific queries
Name 66548 0
Dr Amanda Stafford
Address 66548 0
Emergency Department
Royal Perth Hospital
Wellington Street
Perth 6000
Western Australia
Country 66548 0
Australia
Phone 66548 0
+618 92241741
Fax 66548 0
+618 92247045
Email 66548 0
amanda.stafford@health.wa.gov.au

No information has been provided regarding IPD availability
Summary results
No Results