Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001292268
Ethics application status
Approved
Date submitted
5/07/2018
Date registered
31/07/2018
Date last updated
11/07/2019
Date data sharing statement initially provided
2/11/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Perceptual Effects of Caffeine and Nabilone (PECAN)
Scientific title
Nabilone and caffeine effects on the perceptions of visually, auditory, tactile and multimodal illusions in healthy volunteers
Secondary ID [1] 295440 0
TGA0016889
Universal Trial Number (UTN)
U1111-1216-8090
Trial acronym
PECAN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Psychosis 308698 0
Schizophrenia 308699 0
Condition category
Condition code
Mental Health 307635 307635 0 0
Psychosis and personality disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study 1: caffeine 200 mg capsule taken orally twice in one day by mouth separated by 3 hours on one day, and placebo (glucose powder in capsule, taken orally twice in one day) on the other day, in pseudo-randomised counterbalanced order across participants. Primary purpose to determine if caffeine would be an adequate active placebo for Study 2.
Study 2. Nabilone 2 mg oral capsule twice in one day by mouth, separated by 3 hours on one day, and placebo (either caffeine 200 mg or glucose powder in oral capsule depending on the results of study 1) twice in one day on the other day, in pseudo-randomised counterbalanced order across participants.
Recruitment for each study is undertaken independently.
Intervention code [1] 301750 0
Treatment: Drugs
Comparator / control treatment
This is a double-blind, placebo-controlled, cross-over design (within-subjects design). Each participant has both drug and placebo on different days. In study 1, the placebo is glucose powder in a gelatin capsule, identical to the capsule used for the drug. and in study 2 the placebo is either caffeine (200 mg) twice a day in the same type of capsule or glucose powder depending on the results of study one, investigating the suitability of caffeine as an active placebo.
Control group
Placebo

Outcomes
Primary outcome [1] 306618 0
Effect of nabilone and caffeine on perceptual illusions. The rubber and projected had illusion assess the experience of embodiment and ownership of an inanimate object or image as part of one's own body and the influence of nabilone or caffeine on that experience by self-report questionnaires before and after the illusion, and by a change in the perceived location of one's own hand (unguided by vision). For the Tactile Funnelling Illusion, it is the number of touches felt on the arm, and the distance (cm) one touch is perceived as located relative to the first touch.
Timepoint [1] 306618 0
These will be measured on both days of testing (placebo and drug days). The rubber hand illusion is measured 50 min after second capsule, Projected hand illusion begins 135 min post-capsule 2.
Primary outcome [2] 306619 0
Composite Psychological and Cognitive outcomes, including spatial and digit Working Memory Span tests (SWM and DWM), Schizotypy, measured by a composite z-score derived from the Launey-Slade Hallucination scale (LSH), the Magical Ideation Scale (MIS), the Perceptual Aberration Scale (PAS), the Brief Psychiatric Rating Scale (BPRS) and selected items from the Scale for the Assessment of Positive symptoms (SAPS, Items 15-48). Drug effect self-report questionnaires include The Amphetamine Mood Questionnaire (AMQ), the ARCI marijuana Scale (AMS) and the Marteau and Bekker Self-evaluation scale for anxiety (MBS).
Timepoint [2] 306619 0
AMQ, AMS and MBS are filled in by participants just before taking first capsule, and beginning 30 min after each capsule, and again 120 min and 210 min post-capsule 2. the LSH, MIS, PAS, BPRS and SAPs begin 40 post-capsules (both of them, so twice a day). The SWM test is done once a day, at 50 min post-capsule 1. The DWM is done once a day 110 min post-capsule 1.
Secondary outcome [1] 349052 0
Blood pressure by 3 repeats of a digital blood pressure machine
Timepoint [1] 349052 0
This will be measured on both days of testing (placebo and drug days. They will be assessed 5 times on each of the two test days, at the start of each day before having taken any capsule and 30 min and 2 h after caffeine or its placebo or 60 and 150 min after nabilone and its placebo
Secondary outcome [2] 349217 0
body temperature by 3 repeats of an infrared MediScan digital thermometer measuring supraorbital vein blood temperature
Timepoint [2] 349217 0
Body temperature will be assessed 5 times on each of the two test days, at the start of each day before having taken any drug and 35 and 125 min and 125 h after caffeine or 65 and 155 min after nabilone.
Secondary outcome [3] 349218 0
A saliva sample of 1-2 ml will be taken once each day. This sample will be taken for the purpose of establishing the variant of the COMT gene (gene for the catechol-O-methyl-transferase gene) of each individual. This is to determine if there are differences in the experiences of the illusions, or in the response to drugs, in the two major isoforms of this gene product.
Timepoint [3] 349218 0
One sample will be taken at the beginning of each day, before taking the first capsule.
Secondary outcome [4] 350056 0
Heart rate, measured in triplicate with digital blood pressure machine
Timepoint [4] 350056 0
Gathered at same timepoints as blood pressure
Secondary outcome [5] 350137 0
This is a primary outcome.
Effect of nabilone and caffeine on the Visual Induced Flash illusions. This illusion assess multisensory processing of perceptions of light flashes,
Timepoint [5] 350137 0
This will be measured on both days of testing (placebo and drug days). The Visual Induced Flash Illusion will be tested 90 min after first capsule is taken.
Secondary outcome [6] 350138 0
This is a primary outcome.
Effect of nabilone and caffeine on the Phantom Word Illusion. The outcome measure is the number of novel words heard and their affective ratings.
Timepoint [6] 350138 0
This will be measured on both days of testing (placebo and drug days). Phantom Words Illusion begins 190 min post capsule 2.
Secondary outcome [7] 350139 0
This is a primary outcome.
Effect of nabilone and caffeine on the McGurk effect. The outcome measure is the syllable participants' report hearing, and whether its based on a visual cue or an auditory cue, or is a combination of the two.
Timepoint [7] 350139 0
This will be measured on both days of testing (placebo and drug days). Tactile Funneling Illusion begins 9 min post-capsule 2,

Eligibility
Key inclusion criteria
Inclusion criteria are between the ages of 18 and 59,
Minimum age
18 Years
Maximum age
59 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
pregnant or breastfeeding;
not using a contraceptive if female, fertile and sexually active;
ingesting caffeine on the day of each testing session;
using current prescription medications other than oral contraceptives or acne medication;
using over-the-counter medications in the 48 hours before each testing session; pregnant or breast-feeding;
ingesting caffeine on the day of each testing session,
using current prescription medications other than oral contraceptives or acne medication
using over-the-counter medications in the 48 hours before each testing session/
HAVE:
Heart disease or severe blood vessel disease,
High blood pressure,
Hyperthyroidism,
Tics (muscle twitching usually in the face or shoulders)
Any degenerative disease of the nervous system,
Epilepsy, or other neurological disorders including head injury,
Tourette’s syndrome or a family history of the disorder,
A psychiatric problem for which you are receiving treatment (schizophrenia, depression, anxiety, epilepsy, Parkinson’s, etc)
A serious medical problem for which you are currently receiving treatment (cardiovascular disorders, respiratory disorders, ect),
Had or are currently receiving treatment for substance abuse,
A family history of schizophrenia in your first-degree relatives (parents, children or siblings),
A history of hypersensitivity to any cannabinoids (including cannabis),


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)
Allocation concealment does not apply as this is within-subject cross-over treatment (AB) where the order of treatment is randomised within a blocked (counter-balanced) design, As it is a cross-over study, each participant experiences both conditions, but none of the psychiatrists who conduct the medical and psychiatric exam to determine eligibility, testers or the participant knows on which day they receive drug or placebo. Which day is one is concealed by using the same kind of capsules for both drug and placebo.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation of treatment from a list of possible orders without replacement for each successive block of 24 participants with 12 having placebo first and the 12 with drug first with the restriction that there are no more than 4 sequential participants with the same order.
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
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Pharmacodynamics
Statistical methods / analysis
Either repeated Analysis of Covariance with drug as a within-subject factor, sex of the participants, COMT gene variant, and drug-order as between-subject factors, and with age as a covariate.
We used G*Power 3.1 power calculator, and based our predicted mean difference (Drug-Placebo) and standard deviation of the difference on findings in our lab on the effect of dexamphetamine on the "embodiment" component of the questionnaire assessing changes in the perception of embodiment of the rubber hand, with an effect size of 0.43 (observed under the synchronous condition of the tactile stimulus type condition) with alpha=0.5, with a power of 0.80 (80%), with a two-tailed test and assuming the presence of a sex difference.

For those measures where the data violate the assumptions Analysis of Variance, we will use kernel density estimates with a compare function to determine if the distribution of drug minus placebo differences are significantly different from the null hypothesis distribution (i.e., distribution centered on zero differences), using kernal methods for a permutation test of equality.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
11/07/2018
Date of last participant enrolment
Anticipated
29/06/2023
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
66
Accrual to date
4
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 300031 0
University
Name [1] 300031 0
University of Western Australia
Country [1] 300031 0
Australia
Primary sponsor type
University
Name
University of Western Australia
Address
35 Stirling Highway, Crawley, WA 6009
Country
Australia
Secondary sponsor category [1] 299427 0
None
Name [1] 299427 0
Address [1] 299427 0
Country [1] 299427 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300879 0
The University of Western Australia Human Research Ethics Committee [EC00272]
Ethics committee address [1] 300879 0
Ethics committee country [1] 300879 0
Australia
Date submitted for ethics approval [1] 300879 0
18/06/2018
Approval date [1] 300879 0
29/06/2018
Ethics approval number [1] 300879 0
RA/4/20/4558

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

Contacts
Principal investigator
Name 85138 0
Prof Mathew Martin-Iverson
Address 85138 0
UNIVERSITY OF WESTERN AUSTRALIA, 35 Stirling Highway, Crawley, WA 6009
Country 85138 0
Australia
Phone 85138 0
+61 8 6457 2982
Fax 85138 0
+61 8 6457 3479
Email 85138 0
[email protected]
Contact person for public queries
Name 85139 0
Mathew Martin-Iverson
Address 85139 0
UNIVERSITY OF WESTERN AUSTRALIA, 35 Stirling Highway, Crawley, WA 6009
Country 85139 0
Australia
Phone 85139 0
+61 8 6457 2982
Fax 85139 0
+61 8 6457 3479
Email 85139 0
[email protected]
Contact person for scientific queries
Name 85140 0
Mathew Martin-Iverson
Address 85140 0
UNIVERSITY OF WESTERN AUSTRALIA, 35 Stirling Highway, Crawley, WA 6009
Country 85140 0
Australia
Phone 85140 0
+61 8 6457 2982
Fax 85140 0
+61 8 6457 3479
Email 85140 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
No clear mechanism for sharing available and Ethics protocol confidentiality of data does not include a provision for sharing


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.