Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000411448
Ethics application status
Approved
Date submitted
23/03/2016
Date registered
31/03/2016
Date last updated
5/12/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Open, non-deceptive placebo administration for wound healing
Scientific title
Open, non-deceptive placebo administration to improve the re-epithelialisation rate of 4mm punch biopsy wounds in healthy participants
Secondary ID [1] 288830 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy participants: measuring wound healing rate of a 4mm punch biopsy wound to the upper inner arm. 298109 0
Condition category
Condition code
Skin 298276 298276 0 0
Other skin conditions
Mental Health 298330 298330 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The initial meeting with the study dermatologist will use a scripted introduction to the placebo effect to establish an expectation that placebo administration will be effective. In summary the script describes the following information: The placebo effect is any type of treatment – in this case, a pill – that doesn’t actually contain any drugs or active ingredients. The scientific evidence shows the placebo effect is powerful for conditions like pain and headaches, and previous research has demonstrated that open placebo administration (with participants knowing they were taking placebos) was beneficial for physical health outcomes. This may be because the body is conditioned to respond to taking medications, or because taking the pills increases expectations of an effect. As the brain and immune system are highly interconnected, placebos can affect immune functioning and therefore wound healing. Psychological factors have been shown to affect wound healing in previous research, so it is plausible that expecting benefits through taking placebos would enhance healing.

After this introduction and a final consent form for the wounding procedure, the dermatologist will make the punch biopsy wound. The procedure involves creating a 4 mm punch biopsy wound 7 cm superior to the medial epicondyle of the inner upper arm (the participant chooses which arm), delivered under local anaesthetic and covered with a hydrocolloid dressing and an additional opsite dressing. This wound will be cleaned and the dressing changed at 7 days post-wounding, and again at 10 days.

Treatment will consist of placebo tablets containing lactose monohydrate, microcrystalline cellulose and magnesium stearate as the only 3 ingredients, Participants will be aware that they are receiving inert placebo tablets without active ingredients. Dosage will be two tablets twice per day, starting on the evening of the wounding procedure and continuing daily until the morning of the 10th day after wounding, which is the day the final measures will be taken. Adherence will be measured with a self-report item on the final questionnaire administered at 10 days post-wounding.
Intervention code [1] 294285 0
Treatment: Other
Comparator / control treatment
Participants randomised to the control group will take no treatment subsequent to the wounding procedure.
Control group
Active

Outcomes
Primary outcome [1] 297762 0
Wound healing will be measured from photographs, operationalised as the percentage of the wound area re-epithelialised out of the whole wound area. Wounds are 4mm punch biopsy wounds 7 cm superior to the medial epicondyle of the inner upper arm.
Timepoint [1] 297762 0
Photographs will be taken at 7 days and 10 days after wounding.
Secondary outcome [1] 322285 0
None
Timepoint [1] 322285 0
N/A

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
Participants will be excluded if they smoke, have medical conditions that would affect wound healing (e.g. eczema, psoriasis, anemia, diabetes, etc.), regular use of other treatments affecting wound healing (e.g. anticoagulants, non-steroidal anti-inflammatories), or any surgery or tattoos within the last 30 days.

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 is not concealed to the study dermatologist, who will randomise participants subsequent to the wounding procedure. All follow up measurements and photographs will be taken by the study researcher, who is not aware of allocation, and photographs will not have identifying information by which the dermatologist will be able to determine group allocation of the participant when measuring wound healing.
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 assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
A two-tailed independent samples t-test will be conducted comparing wound area between the open placebo group and the no-treatment control group. Separate analyses will be conducted for 7 days and 10 days post-wounding.

G*Power (version 3.1.9.2) was used to conduct a power analysis to determine the number of participants required. Given an expected effect size of d = 0.7 based on a meta-analysis of wound healing studies (Robinson et al., unpublished manuscript) and a = .05, 68 participants will be required to achieve a power of 80% (i.e. 1-beta = 0.8).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
5/04/2016
Actual
3/05/2016
Date of last participant enrolment
Anticipated
Actual
13/09/2016
Date of last data collection
Anticipated
Actual
23/09/2016
Sample size
Target
68
Accrual to date
Final
70
Recruitment outside Australia
Country [1] 7732 0
New Zealand
State/province [1] 7732 0
Auckland Region

Funding & Sponsors
Funding source category [1] 293191 0
University
Name [1] 293191 0
University of Auckland
Country [1] 293191 0
New Zealand
Primary sponsor type
University
Name
University of Auckland Masters Programme Funding
Address
University of Auckland,
Room 12.017, Level 12,
Auckland Hospital Support Building,
2 Park Road,
Grafton,
Auckland 1023
Country
New Zealand
Secondary sponsor category [1] 291989 0
None
Name [1] 291989 0
None
Address [1] 291989 0
None
Country [1] 291989 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294677 0
University of Auckland Human Participants Ethics Committee (UAHPEC)
Ethics committee address [1] 294677 0
The University of Auckland
Private Bag 92019
Auckland, New Zealand

Level 10, 49 Symonds Street,
Grafton,
Auckland 1010
Ethics committee country [1] 294677 0
New Zealand
Date submitted for ethics approval [1] 294677 0
26/02/2016
Approval date [1] 294677 0
04/04/2016
Ethics approval number [1] 294677 0

Summary
Brief summary
Aim: The aim of the study is to establish if wound healing is faster for participants
taking open-label placebo pills (i.e. known by the participant to be
pharmacologically inert) than participants taking no treatment for their wound
healing.
Hypothesis: Photographs of a 4 mm diameter punch biopsy wound in the inner arm
will show a greater area of re-epithelialisation at 7 days and 10 days after wounding
for participants using daily open placebo treatment than participants using no
treatment.

Summary of the project:
Placebo treatment can be effective for subjective complaints (Miller, Colloca, &
Kaptchuk, 2009) and also results in physiological changes (Finniss et al., 2010),
suggesting that it may be an effective treatment option for some people. However, it
is currently unethical to prescribe placebo treatment, as this typically requires
deception of patients, undermining the principle of informed consent. This study
aims to establish whether open placebo treatment (i.e. placebo administration
without deception, where participants are aware that they are taking placebos) is
effective for wound healing, which would allow patients to benefit from harnessing
placebo effects with full informed consent.
Wound healing rates can be affected by psychosocial factors such as stress (Walburn
et al., 2009), and psychosocial interventions can improve wound healing rates
(Broadbent et al., 2012; Koschwanez et al., 2013). This means that a
psychologically-based treatment such as placebo may affect wound healing rates
through mechanisms such as expectation of improvement or conditioned
physiological effects from ingesting medication (Benedetti & Amanzio, 2013).
Kaptchuk et al. (2010) demonstrated that open placebo treatment was effective for
improving symptoms and functioning for participants with Irritable Bowel Syndrome,
setting a precedent for the use of open placebo treatment to improve participant
outcomes. Given these results, it is worth investigating whether open placebo is
effective in improving wound healing rates in healthy participants.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 817 817 0 0
/AnzctrAttachments/370392-Open Placebo - Ethics submission.pdf
Attachments [2] 818 818 0 0
/AnzctrAttachments/370392-Open placebo (AM) - Research Protocol (v3.2).docx

Contacts
Principal investigator
Name 64626 0
Prof Keith Petrie
Address 64626 0
Room 12.017, Level 12,
Auckland Hospital Support Building,
2 Park Road,
Grafton,
Auckland 1023
Country 64626 0
New Zealand
Phone 64626 0
+64 9 923-6564
Fax 64626 0
Email 64626 0
[email protected]
Contact person for public queries
Name 64627 0
Prof Keith Petrie
Address 64627 0
Room 12.017, Level 12,
Auckland Hospital Support Building,
2 Park Road,
Grafton,
Auckland 1023
Country 64627 0
New Zealand
Phone 64627 0
+64 9 923-6564
Fax 64627 0
Email 64627 0
[email protected]
Contact person for scientific queries
Name 64628 0
Prof Keith Petrie
Address 64628 0
Room 12.017, Level 12,
Auckland Hospital Support Building,
2 Park Road,
Grafton,
Auckland 1023
Country 64628 0
New Zealand
Phone 64628 0
+64 9 923-6564
Fax 64628 0
Email 64628 0
[email protected]

No information has been provided regarding IPD availability


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
SourceTitleYear of PublicationDOI
EmbaseOpen-label Placebos for Wound Healing: A Randomized Controlled Trial.2018https://dx.doi.org/10.1093/abm/kax057
N.B. These documents automatically identified may not have been verified by the study sponsor.