Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000462189
Ethics application status
Approved
Date submitted
13/03/2019
Date registered
20/03/2019
Date last updated
22/04/2020
Date data sharing statement initially provided
20/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Pilot Study: Effect of electrical brain stimulation on mental skills of individuals with long-term cannabis use
Scientific title
Pilot Study: Effects of transcranial Direct Current Stimulation (tDCS) on cognitive functioning in regular, long-term cannabis consumers
Secondary ID [1] 295984 0
nil
Universal Trial Number (UTN)
U1111-1229-7857
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cognition 309497 0
Condition category
Condition code
Neurological 308333 308333 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Individuals will be screened for eligibility using an online survey. This will include customised questions as well as published measures such as the 21-item Depression, Anxiety, and Stress Scale and Alcohol Use Disorder Identification test.

Using a randomised, double-blind and sham-controlled design, we will compare cognitive outcomes following one session of transcranial Direct Current Stimulation (tDCS; HDCStim, Newronika s.r.l Italy), a brain stimulation paradigm, between individuals who use cannabis and a control group of non-drug using individuals.

Participants will receive either active or sham/placebo tDCS on one occasion. Active, anodal tDCS will be provided at 1.5mA for 20 minutes. Anodal stimulation will be used to stimulate cortical excitability of the left dorsolateral prefrontal cortex (DLPFC) while cathodal stimulation will be applied to the right DLPFC. Sham stimulation will involve stimulation for 20 seconds and then will automatically switch off.

The study also involves:
1) Paired Pulse Transcranial Magnetic Stimulation (TMS). ppTMS (120%) will be applied to the primary motor cortex (M1) once prior to and once after tDCS (within approximately 10 minutes after brain stimulation has been terminated). The pre-tDCS TMS session will take approximately 40 minutes including paradigm set-up. The post-tDCS TMS session will take approximately 20 minutes. During paired pulse TMS two consecutive pulses are applied to the skull with a variable inter-stimulus interval (ISI). Short Interval Intracortical Inhibition (SICI) occurs when a sub-threshold conditioning TMS pulse is given one to five milliseconds before a supra-threshold test pulse. SICI provides a measure of GABA-a (inhibitory neurotransmitter).

2) Urinary biomarker analysis. A urine sample will be collected from participants prior to and shortly after tDCS.

3) Objective cognitive measures. Cognitive function will be measured pre-tDCS and post-tDCS using computerised cognitive tasks. We will use the Iowa Gambling Task (measures decision making) and the Go/No Go task (measures inhibitory control) relevant to dorsolateral prefrontal cortex (DLPFC) functioning. The Go/No Go task also involves a motor component relevant to the primary motor cortex (M1). The cognitive tasks will take approximately 20 minutes to complete.

All procedures will be carried out in a Laboratory setting at the University of Tasmania. tDCS will be administered by a registered psychologist with previous experience in brain stimulation paradigms.
Intervention code [1] 312311 0
Treatment: Devices
Comparator / control treatment
Placebo/sham electrical stimulation delivered by tDCS, which will be administered by a registered psychologist with experience in brain stimulation paradigms.

The control group of participants will be non-substance using individuals, with < 50 lifetime uses of cannabis.
Control group
Placebo

Outcomes
Primary outcome [1] 307306 0
Cognitive functioning: Decision making, measured by the Iowa Gambling Task
Timepoint [1] 307306 0
Cognitive functioning (decision making) will be measured pre- and post- tDCS intervention
Primary outcome [2] 319482 0
Cognitive functioning: Inhibitory control, measured by the Go/No-Go Task
Timepoint [2] 319482 0
Cognitive functioning (inhibitory control) will be measured pre- and post- tDCS intervention
Secondary outcome [1] 351431 0
Composite secondary outcome - Urinary amino acid biomarkers:
1. Gamma y-aminobutyric acid
2. L-glutamine
3. Succinic acid
4. Alpha-ketoglutaric acid
5. Catecholaminergic (norepinephrine, epinephrine)
6. Dopamine
7. D,L-tryptophan
8. L-tyrosine
9. p-tyramine
10. Serotonergic
11. L-kynurenine
12. L-ornithine
Timepoint [1] 351431 0
Urine samples will be obtained pre- and post- tDCS intervention

Eligibility
Key inclusion criteria
General inclusion criteria: 18-50 years old, male and female, English-speakers, normal or corrected-to-normal vision

Cannabis group inclusion criteria: Individuals who have regularly (1+ days per week) used cannabis for 1+ year. We are not specifically recruiting individuals with cannabis use disorder (CUD); however, participants may meet criteria for CUD. Cannabis users will be asked to refrain from cannabis use 24 hours + prior to the Research Session.

Control group: No history of cannabis use or minimal (<50 lifetime uses) history of cannabis use
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
General exclusion criteria:
• No current or recent illicit drug use (in the past 30 days)
• Dependence on alcohol (a dependency score of 20 or more on the Alcohol Use Disorder Identification Test) or other illicit substances, except nicotine
• Pregnancy or suspected pregnancy
• Known psychological problems (e.g., depression, anxiety, schizophrenia, PTSD); participants who self-report a clinical diagnosis will be excluded from the study,
• Physical conditions or problems (such as cardiac problems and using related medication such as beta-blockers)
• Metabolic diseases that would confound measures of metabolites (e.g., renal and kidney disease, phenylketonuria/PKU, tyrosinemia)
• Use of prescribed medications to treat psychological conditions (e.g., anxiolytics, antidepressants) due to the potential interactive effect between tDCS and particular medications that could affect measures of cortical excitability

Brain stimulation contraindications:
• Epilepsy or family history of epilepsy
• History of neuropsychiatric conditions (e.g., stroke)
• Skin compromised by pre-existing or current burns (e.g., sun burn), injuries, or conditions affecting the scalp (eczema or psoriasis on the head)
• Pre-existing implants such as pacemakers and metal implants (excluding dental work such as tooth fillings, dental implants and non-ferromagnetic material). Any implant that is conductive, ferromagnetic or contains other magnetic-sensitive metals such as cochlea implants, stents, or implanted stimulators are contraindicated for TMS
• Implanted electronic devices or intracranial magnetic clips such as aneurysm clips
• Serious head injury or neurosurgery

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 by computer that will be completed by an independent researcher. The tDCS stimulation pre-programming will be completed also by an independent researcher to maintain blinding.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation (computer generated)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Pre-post analysis using ANOVA (or ANCOVA for any identified covariates)

We aim to recruit between 14-18 participants per group. To obtain a moderate effect size, a total sample of approximately 28 would be needed. Similar research conducted by Oliveira et al. (2013) used a randomised, double-blind, parallel group design with 14 participants per group and found a moderate to large effect (Hedge's g of .65). G*power (Faul, Erdfelder, Lang, & Buchner, 2017) calculations showed a total sample of 36 (18 participants per group) would be needed to obtain a moderate effect size (f of .25).

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Safety concerns
Date of first participant enrolment
Anticipated
10/09/2019
Actual
10/09/2019
Date of last participant enrolment
Anticipated
20/04/2020
Actual
19/03/2020
Date of last data collection
Anticipated
5/05/2020
Actual
19/03/2020
Sample size
Target
28
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
TAS
Recruitment postcode(s) [1] 25460 0
7001 - Hobart

Funding & Sponsors
Funding source category [1] 300578 0
University
Name [1] 300578 0
University of Tasmania
Country [1] 300578 0
Australia
Primary sponsor type
University
Name
University of Tasmania
Address
Churchill Avenue,
Sandy Bay Campus,
Hobart
Tasmania
7005
Country
Australia
Secondary sponsor category [1] 300072 0
None
Name [1] 300072 0
Address [1] 300072 0
Country [1] 300072 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301367 0
Tasmanian Health and Medical Human Research Ethics Committee
Ethics committee address [1] 301367 0
Ethics committee country [1] 301367 0
Australia
Date submitted for ethics approval [1] 301367 0
17/09/2018
Approval date [1] 301367 0
23/01/2019
Ethics approval number [1] 301367 0
H0017713

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

Contacts
Principal investigator
Name 86770 0
Dr Michael Garry
Address 86770 0
Room 134
Private Bag 30
Social Science Building
Sandy Bay campus
University of Tasmania
Hobart
Tasmania
7001
Country 86770 0
Australia
Phone 86770 0
+61 3 6226 2204
Fax 86770 0
Email 86770 0
[email protected]
Contact person for public queries
Name 86771 0
Monica Lovell
Address 86771 0
Private Bag 30
Social Science Building
Sandy Bay campus
University of Tasmania
Hobart
Tasmania
7001
Country 86771 0
Australia
Phone 86771 0
+61 3 6226 7458
Fax 86771 0
Email 86771 0
[email protected]
Contact person for scientific queries
Name 86772 0
Monica Lovell
Address 86772 0
Room 108
Psychology Research Centre,
Clark Road,
University of Tasmania
Hobart
Tasmania
7001
Country 86772 0
Australia
Phone 86772 0
+61 3 6226 7458
Fax 86772 0
Email 86772 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
We will not be sharing data due to the sensitive nature of the study


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.