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Trial registered on ANZCTR


Registration number
ACTRN12621001150831
Ethics application status
Approved
Date submitted
15/07/2021
Date registered
26/08/2021
Date last updated
26/08/2021
Date data sharing statement initially provided
26/08/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
How Does Choice Influence Drug Response?
Scientific title
How Does Choice Influence Side Effect Reporting in Response to an Inert Medication in Healthy Adults?
Secondary ID [1] 304767 0
None.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nocebo effect 322820 0
Attention to negative information 322821 0
Condition category
Condition code
Mental Health 320410 320410 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Previous research has shown that reducing patient choice both leads to higher levels of nocebo responding and diminishes the placebo effect (Bartley et al., 2016). This study seeks to explore the mechanisms through which this process occurs. One possibility is that reducing choice focuses attention to negative information about the medication. This study will investigate whether limiting choice will increase recall of negative information and influence both placebo and nocebo responding. As the medication in this research will be a placebo, reported side effects will be nocebo effects (the negative side effects of an inert agent) and reported medication efficacy will be placebo effects. The placebo itself comprises a capsule containing lactose monohydrate, microcrystalline cellulose and magnesium stearate, and will be administered orally at a single time point during the intervention session. Participation will involve randomisation to either a choice group (in which participants will select one of two “beta blockers” to take) or a no-choice group (participants will be led to believe that they will randomly receive one of the two beta blockers, when in actual fact, they will receive their non-preferred option). Participants will receive a beta blocker information brochure, which was designed specifically for this study and gives an overview of the mechanisms of beta blockers, their potential side effects, and how they may be useful for anxiety. After taking the placebo, participants will wait 10 minutes, and will be told that during this time period, the beta blocker should take effect. Immediately following this latent period, they will take part in 3 short tasks to simulate an examination setting (these include digit span, digit symbol matching, and a recall task). Heart rate and blood pressure measurements will be recorded at three time points throughout the session, along with questionnaires about anxiety and side effects. It is expected that the 3 exam-simulating tasks will take participants 15 minutes to complete. The overall session, including the completion of questionnaire and the repeated measurements of heart rate and blood pressure, will take 50 minutes total. The following day, participants will complete a brief follow-up questionnaire on anxiety and side effects experienced over the prior 24 hours. This will be sent via a link and completed online.
Intervention code [1] 321154 0
Behaviour
Comparator / control treatment
After completion of baseline questionnaires and measurements, participants will receive information about the two types of beta blockers, Lopressor and betacarm, and all participants will be provided with a form to select their preferred beta blocker option.

Participants will then be randomized to a 'choice' or a 'no-choice' group, Those in the comparator 'no-choice' group will be informed that they will now be randomized to receive either betacarm, or Lopressor. In actual fact, 'no-choice' group participants will receive their non-preferred option. Participants in the comparator group will also undergo the same assessments and questionnaires as the 'choice' group

Control group
Placebo

Outcomes
Primary outcome [1] 328251 0
Side effect reporting - measured through the Side Effect Attribution Scale (SEAS) (Mackrill et al., 2020).
Timepoint [1] 328251 0
10 minutes after participants take the beta blocker
Immediately following completion of the exam-simulating tasks
24 hours after taking part in the in-person session
Primary outcome [2] 328252 0
State anxiety, assessed using a short version of the State-Trait Anxiety Inventory
Timepoint [2] 328252 0
At baseline
10 minutes after participants take the beta blocker
Immediately following completion of the exam-simulating tasks
24 hours after taking part in the in-person session
Secondary outcome [1] 398255 0
Blood pressure, using a sphygmomanometer
Timepoint [1] 398255 0
At baseline
10 minutes after participants take the beta blocker
Immediately following completion of the exam-simulating tasks
Secondary outcome [2] 398256 0
Heart rate, measured by an iHealth Wireless Blood Pressure Monitor
Timepoint [2] 398256 0
At baseline
10 minutes after participants take the beta blocker
Immediately following completion of the exam-simulating tasks

Eligibility
Key inclusion criteria
18+ years old
English speaking
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
The research necessitates that those participating believe that they are taking a beta blocker. As such, exclusion criteria is as follows:

Those already taking beta blockers
Those taking taking calcium channel blocker medications or digoxin, which are known to interfere with beta blockers
Those with any conditions with which beta blockers are unable to be taken –
such as low heart rate or blood pressure, bronchospasms, diabetes, asthma
Those with any known reactions to beta blockers
Those who are pregnant, or trying to get pregnant.



Study design
Purpose of the study
Educational / counselling / training
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
This was done via sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
This was achieved using a randomisation table created by computer software.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
A total of 82 participants are required to detect a medium effect size in the difference in the number of symptoms reported between
the choice and no choice groups, at an alpha level of .05.
As such, the intention is to recruit 41 participants in each group (those provided with a choice of medication, and those allocated a
medication).

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 outside Australia
Country [1] 23966 0
New Zealand
State/province [1] 23966 0
Auckland

Funding & Sponsors
Funding source category [1] 309138 0
University
Name [1] 309138 0
University of Auckland
Address [1] 309138 0
Department of Psychological Medicine, University of Auckland
85 Park Road, Grafton, Auckland, 1023
Country [1] 309138 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
Department of Psychological Medicine, University of Auckland
85 Park Road, Grafton, Auckland, 1023
Country
New Zealand
Secondary sponsor category [1] 310092 0
None
Name [1] 310092 0
Address [1] 310092 0
Country [1] 310092 0
Other collaborator category [1] 281913 0
University
Name [1] 281913 0
University of New South Wales
Address [1] 281913 0
High St
Kensington, NSW 2052
Australia
Country [1] 281913 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309005 0
University of Auckland Human Participants Ethics Committee
Ethics committee address [1] 309005 0
University of Auckland Office of Research Strategy and Integrity
Level 3, 49 Symonds Street
Private Bag 92019
Auckland 1142
Ethics committee country [1] 309005 0
New Zealand
Date submitted for ethics approval [1] 309005 0
07/07/2021
Approval date [1] 309005 0
19/07/2021
Ethics approval number [1] 309005 0
UAHPEC22835

Summary
Brief summary
Previous research has shown that reducing choice both leads to higher levels of nocebo responding and diminishes the placebo effect (Bartley, Faasse, Horne & Petrie, 2016). This study seeks to explore the mechanisms through which this process occurs. One
possibility is that reducing choice focuses attention on negative information about medication. In a study where participants are randomised to either get a choice of medication or not, we investigate whether a lack of choice increases focus and recall of negative information about a medication. As the medication in this research will be a placebo, reported side effects will be nocebo effects (the reported side effects from an inert agent) and reported medication efficacy will be placebo effects.
Hypothesis 1: Providing participants with a choice in medication will result in fewer nocebo effects and greater placebo response than participants who have been given no choice of medication (replication of Bartley et al. 2016).
Hypothesis 2: The no choice group will show a greater recall of negative information supplied about the medication.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112626 0
Prof Keith Petrie
Address 112626 0
Department of Psychological Medicine
University of Auckland
85 Park Road
Grafton, 1023
Auckland
Country 112626 0
New Zealand
Phone 112626 0
+64211117222
Fax 112626 0
Email 112626 0
kj.petrie@auckland.ac.nz
Contact person for public queries
Name 112627 0
Prof Keith Petrie
Address 112627 0
Department of Psychological Medicine
University of Auckland
85 Park Road
Grafton, 1023
Auckland
Country 112627 0
New Zealand
Phone 112627 0
+64211117222
Fax 112627 0
Email 112627 0
kj.petrie@auckland.ac.nz
Contact person for scientific queries
Name 112628 0
Prof Keith Petrie
Address 112628 0
Department of Psychological Medicine
University of Auckland
85 Park Road
Grafton, 1023
Auckland
Country 112628 0
New Zealand
Phone 112628 0
+64211117222
Fax 112628 0
Email 112628 0
kj.petrie@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data will be available only to the research team for the purposes of analysis.
What supporting documents are/will be available?
Informed consent form
How or where can supporting documents be obtained?
Type [1] 12530 0
Informed consent form
Citation [1] 12530 0
Link [1] 12530 0
Email [1] 12530 0
Other [1] 12530 0
Summary results
No Results