ANZCTR - Registration

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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]

nil

Universal Trial Number (UTN)

U1111-1229-7857

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Cognition

Condition category

Condition code

Neurological

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]

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]

Cognitive functioning: Decision making, measured by the Iowa Gambling Task

Timepoint [1]

Cognitive functioning (decision making) will be measured pre- and post- tDCS intervention

Primary outcome [2]

Cognitive functioning: Inhibitory control, measured by the Go/No-Go Task

Timepoint [2]

Cognitive functioning (inhibitory control) will be measured pre- and post- tDCS intervention

Secondary outcome [1]

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]

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

TAS

Recruitment postcode(s) [1]

7001 - Hobart

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Tasmania

Address [1]

Churchill Avenue,
Sandy Bay Campus,
Hobart
Tasmania
7005

Country [1]

Australia

Primary sponsor type

University

Name

University of Tasmania

Address

Churchill Avenue,
Sandy Bay Campus,
Hobart
Tasmania
7005

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Tasmanian Health and Medical Human Research Ethics Committee

Ethics committee address [1]

Research Ethics and Integrity Unit 
Office of Research Services 
Private Bag 1 
Hobart 
Tasmania
Australia
7001

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

17/09/2018

Approval date [1]

23/01/2019

Ethics approval number [1]

H0017713

Summary

Brief summary

Long-term cannabis use is associated with deficits in areas of cognitive functioning. It is important to intervene at the cognitive level as cognitive deficits impede everyday functioning (i.e., driving) and health outcomes for individuals who have engaged in prolonged substance use (Aharonovich, Brooks, Nunes, & Hasin, 2008; Cousijn & Filbey, 2015; Sofuoglu, DeVito, Waters, & Carroll, 2013). For example, poor inhibitory control can reduce the ability to refrain from drug use and hence increase the risk of relapse (Goldstein & Volkow, 2002). There is a need to provide cognitive intervention to cannabis users to 1) improve everyday functioning, and 2) alleviate cognitive problems to hopefully empower individuals to cease cannabis.

Pharmacological interventions are being investigated for assisting drug abstinence, however, such treatment often has unwanted side effects (e.g., headaches, suicidality) and typically does not result in long-term abstinence (Le Foll, Gorelick, & Goldberg, 2009; Levin et al., 2011; McRae-Clark et al., 2015; Schoedel et al., 2011). Pharmacological interventions at the cognitive level has received less attention and existing studies provide mixed results across populations (Boggs et al., 2018; Hindocha et al., 2018; McGuire et al., 2017; Solowij et al., 2018). Moreover, novel pharmacotherapies can be exorbitantly priced and some have restricted access in Australia. In various reviews, researchers emphasise that effective cognitive-enhancing interventions need to be identified as there are few successful pharmacotherapy options for assisting cognitive problems among people who use substances, such as cannabis (Coles, Kozak, & George, 2018; Cousijn, 2015; Flöel, 2014). Cognitive training has received some attention but with mixed results and researchers are now investigating brain stimulation techniques to target cognitive-related brain regions, such as the dorsolateral prefrontal cortex. 

The aim of this pilot study is to determine the feasibility of using transcranial Direct Current Stimulation (tDCS; HDCStim, Newronika s.r.l. Italy) to enhance cognitive functioning in individuals who have engaged in long-term, regular cannabis use. We will provide a single session of tDCS (20 minutes, 1.5mA, DLPFC) and measure decision making and inhibitory control before and after tDCS. Urine will also be collected before and after tDCS in order to investigate potential urinary biomarkers (specifically, a panel of amino acids such as glutamine and GABA) of cognition in relation to cannabis use. 

Our hypothesis is that cognitive functioning, as measured by objective cognitive tests, will increase from pre- to post-tDCS and that changes in urinary biomarkers will be associated with changes in cognitive functioning as a result of tDCS. The group of individuals who use cannabis are expected to show greatest improvements in cognition compared to the control group.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Michael Garry

Address

Room 134
Private Bag 30
Social Science Building
Sandy Bay campus
University of Tasmania
Hobart
Tasmania
7001

Country

Australia

Phone

+61 3 6226 2204

Fax

Michael.Garry@utas.edu.au

Contact person for public queries

Name

Monica Lovell

Address

Private Bag 30
Social Science Building
Sandy Bay campus
University of Tasmania
Hobart
Tasmania
7001

Country

Australia

Phone

+61 3 6226 7458

Fax

Monica.Lovell@utas.edu.au

Contact person for scientific queries

Name

Monica Lovell

Address

Room 108
Psychology Research Centre,
Clark Road,
University of Tasmania
Hobart
Tasmania
7001

Country

Australia

Phone

+61 3 6226 7458

Fax

Monica.Lovell@utas.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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

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No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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