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Trial registered on ANZCTR


Registration number
ACTRN12616001176459
Ethics application status
Approved
Date submitted
21/07/2016
Date registered
26/08/2016
Date last updated
26/08/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
How do side effects influence perceived drug effectiveness?
Scientific title
The influence of induced local side effects on perceived drug effectiveness in healthy participants?
Secondary ID [1] 289709 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
the mechanisms by which the number and type of side effects experienced by healthy individuals will influence their perceived efficacy of medications. 299524 0
Condition category
Condition code
Mental Health 299501 299501 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
At the initial study session participants will meet with the researcher (Masters student) who will use a scripted cover story to mask the actual psychological investigation of the study. Deception is necessary to ensure the validity and integrity of the study. If participants were aware of the true psychological aims of the study to investigate how side effects impact placebo-nocebo responses, this may influence their own expectations and responses to the medication. The cover story is based on research that increasing levels of oxygen in the brain can improve memory formation in healthy young adults (Moss & Scholey, 1996).

Following the scripted introduction to the research session written informed consent will be collected. Baseline and follow up questionnaires will gather information including demographic, mood state, perceived sensitivity to medications, symptom reports, standardized memory function tasks, lung function, breathing sensations, and following administration of a nasal spray participants' perceptions of the efficacy of the medication on memory function and breathing status will be collected.

Participants will be told they will be randomized to take either a nasal spray medication containing the active ingredient Salbutamol (a bronchodilator) in a pediatric equivalent dose, or a control medication not containing the active ingredient. As a cover story, participants will also be told that we believe by improving lung function more oxygen will be delivered to the circulatory system which will result in elevated oxygen levels in the brain, with the flow on effect of improving memory formation. In order to maintain the cover story participants will perform two standardized memory function tasks and a spirometer lung function test before and after taking the nasal spray medication.

In reality all nasal sprays in the experimental groups will contain graduated dilutions of capsaicin (originally 3% in sesame oil) as the active placebo ingredient in order to induce local side effects. The nasal spray solutions are mixed in a university bio-engineering laboratory by a senior technician, and tested with a focus group representative of the target population. Participants will be randomized to one only of the four intervention groups and will take one dose only of either nil, low, medium or high (relative to each other) doses of the solution containing capsaicin.

The doses of 3% capsaicin in sesame oil (microlitre) and saline (ml) are diluted as follows:
High group - 0.0165 microlitre/1ml
Medium group - 0.0041250 microlitre/1ml
Low group - 0.00103120 microlitre/1ml
Nil - saline only

Treatment will involve participants self-administering one dose of the solution as one spray only into each nostril. Each spray of the applicator will deliver 0.01ml of solution. Participants will also be told the spray may also cause minor side effects including a prickling sensation in the nose, elevated heart rate, headache, tremor, feeling jittery, dry mouth, dry or irritated nose and throat, chest discomfort, nausea, drowsiness, dizziness and light headedness. Participants will be asked to gently inhale the medication and to sit quietly for 15 minutes in order for the medication to take effect. After this resting period follow up measures and tests will be administered in the same order as prior to administration of the nasal spray. Following the research session participants will be told any medication effect will dissipate within two hours.

The active placebo contains graduated dilutions of 3% capsaicin (in sesasme oil) in saline. While high concentrations of capsaicin have an analgesic effect, the concentrations we deliver are minimal and not harmful. Th solutions will cause a slight prickling sensation in the nasal pathway. A previous study of 144 participants has shown that a similar formula is well tolerated and causes no adverse effects aside from mild prickling sensations
(Rief & Glombiewski, 2012). In our own recent study looking at the effect of price on place and nocebo effects conducted last year, we found at the dose similar to that used in the high side effect group in this study that the spray caused transient nasal prickling and irritated nose symptom reports for a few minutes following the nasal spray administration. No other adverse events were reported.

Following the analysis of results, all participants will be emailed a debriefing sheet with full disclosure of the actual study aims, and an offer to meet with the researchers to discuss any concerns a participant may have regarding the study protocol.
Intervention code [1] 295335 0
Treatment: Other
Comparator / control treatment
The control group will be administered a saline solution without the active placebo ingredient. In other respects the procedure remains the same for all participants.
Control group
Placebo

Outcomes
Primary outcome [1] 298986 0
Perceptions of the efficacy of the nasal spray, assessed via self-report using a two item questionnaire (likert scale 0-10).
item 1: How effective was the medication that you took today for improving your breathing?
item 2: How effective was the medication that you took today for improving your memory?
Timepoint [1] 298986 0
20 minutes post-medication administration
Secondary outcome [1] 325823 0
Lung function will be measured with a Vitalograph Hand Held COPD-6 Spirometer. The first outcome measure to be compared is FEV1% predicted against normative population values for age, height, weight, gender (Forced Expiratory Volume - in this case the amount of air forcibly exhaled in 1 second)
Timepoint [1] 325823 0
The first outcome measure of lung function as FEV1% predicted will be collected prior to and post administration of a nasal spray, approximately 20 minutes apart.
Secondary outcome [2] 326925 0
Working memory function tasks:
1 - Rey Verbal Learning Test - a modified version suitable to our study
2 - WAIS-IV Forward Backward Digit Span
Timepoint [2] 326925 0
Measures of memory function will be collected prior to and post administration of a nasal spray, approximately 20 minutes apart.
Secondary outcome [3] 327129 0
Lung function will be measured with a Vitalograph Hand Held COPD-6 Spirometer. The second lung function outcome measure to be compared is FVC% predicted against normative population values for age, height, weight, gender (Forced Vital Capacity - the amount of air exhaled over 5 seconds, the duration of the FEV test)
Timepoint [3] 327129 0
The second outcome measure of lung function as FVC% predicted will be collected prior to and post administration of a nasal spray, approximately 20 minutes apart.

Eligibility
Key inclusion criteria
Healthy participants who are able to understand and write in English
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
smoker
diagnosed illness (e.g. asthma/COPD)
taking antidepressants
taking beta blockers
taking bronchodilator medications

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 to condition is concealed to the researcher conducting the screening interview and the research sessions. Randomisation procedures were undertaken by a PhD candidate not involved in the research project. All materials for the research session are contained in numbered opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation.
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

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
4/07/2016
Date of last participant enrolment
Anticipated
30/09/2016
Actual
Date of last data collection
Anticipated
30/09/2016
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment outside Australia
Country [1] 8042 0
New Zealand
State/province [1] 8042 0
Auckland

Funding & Sponsors
Funding source category [1] 294096 0
University
Name [1] 294096 0
The University of Auckland
Country [1] 294096 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland Masters Programme Funding
Address
The University of Auckland
Room 12.017, Level 12
Auckland City Hospital Support Building
2 Park Rd
Grafton
Auckland 1023
Country
New Zealand
Secondary sponsor category [1] 292928 0
None
Name [1] 292928 0
None
Address [1] 292928 0
None
Country [1] 292928 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295512 0
UNIVERSITY OF AUCKLAND HUMAN PARTICIPANTS ETHICS COMMITTEE (UAHPEC)
Ethics committee address [1] 295512 0
The University of Auckland
Private Bag 92019
Auckland, New Zealand

Level 10,
49 Symonds Street,
Grafton 1010,
Auckland
Ethics committee country [1] 295512 0
New Zealand
Date submitted for ethics approval [1] 295512 0
Approval date [1] 295512 0
10/05/2016
Ethics approval number [1] 295512 0
017184

Summary
Brief summary
Side effects are a common occurrence with many medical treatments but their influence on the placebo-nocebo effect has not been explored. In a placebo study purportedly examining how the drug Salbutamol influences memory we will actually examine how different levels of local side effects from a nasal spray influence drug effectiveness.

We hypothesise that higher levels of side effects will be associated with a greater level of actual and perceived drug effectiveness. In this study we will use a nasal spray that purportedly increases lung function. In reality all nasal sprays given will be placebos but with varying degrees of local nasal sensation caused by different levels of capsaicin.

We hypothesise that participants who receive the nasal spray with more local side effects will show a greater placebo effect – the medication will be more effective in improving lung function markers (assessed using FEV1, FVC and FEV1/FVC ratio), memory performance, and perceived medication efficacy for memory and breathing sensations than for participants who receive the medication with lower or no local side effects.

Previous research has demonstrated that patient’s expectations play an important role in the efficacy of medical treatments (Bingel et al., 2011; Faasse & Petrie, 2013). It is believed that side effects have an important influence on expectations, with greater levels of side effects influencing the perception of the medication as being more powerful and therefore generating a larger placebo response. Conversely, medications with no or very mild side effects may be seen as weaker. This study will investigate whether using a medication with no or low side effects will result in poorer efficacy (a reduced placebo or nocebo effect) when compared to using a medication that has more side effects.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 967 967 0 0
/AnzctrAttachments/371117-Ethics_Outcome_ Approved_10May2016.pdf

Contacts
Principal investigator
Name 67526 0
Prof Keith Petrie
Address 67526 0
Room 12.017, Level 12
Auckland City Hospital Support Building
2 Park Rd
Grafton
Auckland 1023
Country 67526 0
New Zealand
Phone 67526 0
+64 9 923 6564
Fax 67526 0
Email 67526 0
[email protected]
Contact person for public queries
Name 67527 0
Keith Petrie
Address 67527 0
Room 12.017, Level 12
Auckland City Hospital Support Building
2 Park Rd
Grafton
Auckland 1023
Country 67527 0
New Zealand
Phone 67527 0
+64 9 923 6564
Fax 67527 0
Email 67527 0
[email protected]
Contact person for scientific queries
Name 67528 0
Keith Petrie
Address 67528 0
Room 12.017, Level 12
Auckland City Hospital Support Building
2 Park Rd
Grafton
Auckland 1023
Country 67528 0
New Zealand
Phone 67528 0
+64 9 923 6564
Fax 67528 0
Email 67528 0
[email protected]

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No Supporting Document Provided



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