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Trial registered on ANZCTR


Registration number
ACTRN12620001080910
Ethics application status
Approved
Date submitted
20/08/2020
Date registered
20/10/2020
Date last updated
28/01/2024
Date data sharing statement initially provided
20/10/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Open-label placebo for insomnia (OPIN)
Scientific title
Open-label placebo for insomnia (OPIN): a cohort multiple randomized controlled trial in adults with moderate or severe insomnia
Secondary ID [1] 300018 0
None
Universal Trial Number (UTN)
U1111-1244-9305
Trial acronym
OPIN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Insomnia 315514 0
Condition category
Condition code
Mental Health 313799 313799 0 0
Other mental health disorders
Neurological 313800 313800 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants with insomnia symptoms are initially recruited to a large observational cohort to measure changes in insomnia symptoms over a 4-week period as an outcome variable. After two weeks of this observation period, participants will be randomised to one of three different arms. Participants randomized into arm 1 will receive an invite to trial open-label placebo, those in arm 2 will receive an invite to trial conventional placebo, and a third arm will receive no invite (observational control).
In both arm 1 and arm 2, the investigational product is placebo capsules (i.e. capsules containing microcrystalline cellulose). Participants are instructed to take 2 capsules (oral) per day for 2 weeks, 10-15 minutes before they go to bed.
Participants in arm 1 (open-label placebo) are informed that the capsules are placebo capsules (i.e. they contain an inert agent), but provided with a brief rationale as to how placebos may be effective.
Participants in arm 2 (conventional placebo) are informed that the capsules are a new pharmacological agent [7 digit code name] that can reduce insomnia symptoms, and provided with a brief rationale as to how this drug may be effective.
Adherence with placebo capsules will be assessed by asking participants to self-report whether and when they took their capsules each day, as part of a sleep diary. Participants will also be asked to return any unused capsules to their final study site visit.
Intervention code [1] 316290 0
Treatment: Other
Comparator / control treatment
The control group is a no-treatment control.
Control group
Active

Outcomes
Primary outcome [1] 322204 0
Changes in self-reported insomnia symptoms, measured using the Insomnia Severity Index (ISI).
Timepoint [1] 322204 0
Screening, Baseline (Day 14) and Post-treatment (Day 28)
Secondary outcome [1] 377703 0
Rate of uptake of open-label placebo relative to conventional placebo. Rate of uptake of open-label will be measured as the proportion of participants whose written consent to participate in this treatment arm is obtained, relative to the number of participants randomly allocated and invited to participate in this treatment arm. Similarly, rate of uptake to conventional placebo will be measured as the proportion of participants who consent to participate relative to the number of participants invited to participate in this treatment arm.
Timepoint [1] 377703 0
Baseline (randomisation, Day 14)
Secondary outcome [2] 377704 0
Changes in objective sleep parameters, calculated from sleep-wake data collected with an actigraphy watch
Timepoint [2] 377704 0
Daily from Enrolment (Day 1) to Baseline (Day 14).
Daily from Baseline (Day 14) to Post-treatment (Day 28)
Secondary outcome [3] 377705 0
Changes in subjective sleep parameters, assessed using the Consensus Sleep Diary (CSD)
Timepoint [3] 377705 0
Daily from Enrolment (Day 1) to Baseline (Day 14)
Daily from Baseline (Day 14) to Post-treatment (Day 28)
Secondary outcome [4] 377706 0
Changes in daytime fatigue, measured using the Fatigue Symptom Inventory (FSI)
Timepoint [4] 377706 0
Baseline (Day 14) and Post-treatment (Day 28)
Secondary outcome [5] 377707 0
Changes in depression, measured using the Depression, Anxiety Stress Scales - 21(DASS-21)
Timepoint [5] 377707 0
Baseline (Day 14) and Post-treatment (Day 28)
Secondary outcome [6] 377708 0
Changes in anxiety, measured using the Depression, Anxiety Stress Scales - 21(DASS-21)
Timepoint [6] 377708 0
Baseline (Day 14) and Post-treatment (Day 28)
Secondary outcome [7] 377709 0
Changes in stress, measured using the Depression, Anxiety Stress Scales - 21(DASS-21)
Timepoint [7] 377709 0
Baseline (Day 14) and Post-treatment (Day 28)
Secondary outcome [8] 377711 0
Changes in Expectancy, measured by purpose-built Expectancy Measure
Timepoint [8] 377711 0
Baseline, post-randomisation (Day 14) and Post-treatment (Day 28)
Secondary outcome [9] 377715 0
Changes in treatment satisfaction, measured using the Treatment Satisfaction Questionnaire for Medication - II (TSQM-II).
Timepoint [9] 377715 0
Post-treatment (Day 28)
Secondary outcome [10] 377716 0
Self-reported side effects, measured using the Generic Assessment of Side Effects (GASE). No known or possible side effects are expected given the treatment is placebo.
Timepoint [10] 377716 0
Post-treatment (Day 28)

Eligibility
Key inclusion criteria
- Adults (age 18 and above)
- Reporting insomnia symptoms of moderate or greater severity (score on the ISI >= 10)
- Ability and willingness to comply with study protocol
- Proficient in English
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Sleep disorder other than insomnia (e.g. sleep apnoea).
- Serious medical illness requiring invasive treatment/surgery (e.g. cancer) or heavy substance use
- Severe psychiatric comorbidity (e.g. psychosis) or risk of self harm or suicidality
- Currently taking regular (i.e. >=1/week) medication for sleep (including prescription and over-the-counter medications, herbal supplements, homeopathic formulations)
- Current psychological treatment for sleep
- Currently pregnant, planning a pregnancy in the next 3 months, breastfeeding or post-partum < 1 year
- Currently undertaking regular shift work
- Intending to travel to a destination >2 hours’ time difference in the next 3 months

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated randomisation table
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Cohort multiple randomised controlled trial design(cmRCT), All participants enter 2 week observational period, followed by randomisation into one of 3 different groups/arms: open-label placebo, conventional (deceptive) placebo, or observational control.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
To detect an effect size for open-label placebo versus conventional placebo of d=.5, 64 participants in each placebo arm is required to achieve 80% power with alpha=.05. Using an allocation of 2:2:1, a total of 160 participants is required. However, as a 2-stage consent process is employed with a cmRCT design, there is the likelihood that some participants who consent to the first stage (observation) will not accept the invitation to receive treatment (open-label or conventional placebo) in the second stage. To ensure an adequate sample size is obtained in the treatment arms, we will therefore recruit until we have at least 64 participants who accept the invitation to each of the treatment arms.

Primary, Intention-to-treat (ITT) analysis will be used to compare effects of each group (open-label, conventional, observational control) on insomnia symptoms. Primary endpoint (mean ISI scores post-treatment) will be assessed using a mutlilevel model with group and baseline ISI score inluded as factors. Sensitivity analysis, using a per-protocol approach will be implemented as a secondary analysis and include only those participants who complete the study.

Chi-squared independence test will be used to determine differences in uptake to open-label versus conventional placebo treatment.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
2/11/2020
Actual
1/04/2021
Date of last participant enrolment
Anticipated
31/05/2024
Actual
Date of last data collection
Anticipated
21/06/2024
Actual
Sample size
Target
192
Accrual to date
97
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 304471 0
University
Name [1] 304471 0
The University of Sydney
Country [1] 304471 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
University of Sydney
NSW 2006
Country
Australia
Secondary sponsor category [1] 307370 0
None
Name [1] 307370 0
Address [1] 307370 0
Country [1] 307370 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304903 0
The University of Sydney Human Research Ethics Committee
Ethics committee address [1] 304903 0
Ethics committee country [1] 304903 0
Australia
Date submitted for ethics approval [1] 304903 0
22/05/2019
Approval date [1] 304903 0
06/09/2019
Ethics approval number [1] 304903 0
2019/552

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

Contacts
Principal investigator
Name 98594 0
A/Prof Ben Colagiuri
Address 98594 0
A19 - Griffith Taylor
The University of Sydney
NSW 2006 Australia
Country 98594 0
Australia
Phone 98594 0
+61 2 93514589
Fax 98594 0
Email 98594 0
[email protected]
Contact person for public queries
Name 98595 0
Ben Colagiuri
Address 98595 0
A19 - Griffith Taylor
The University of Sydney
NSW 2006 Australia
Country 98595 0
Australia
Phone 98595 0
+61 2 93514589
Fax 98595 0
Email 98595 0
[email protected]
Contact person for scientific queries
Name 98596 0
Ben Colagiuri
Address 98596 0
A19 - Griffith Taylor
The University of Sydney
NSW 2006 Australia
Country 98596 0
Australia
Phone 98596 0
+61 2 93514589
Fax 98596 0
Email 98596 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified participant data collected during the trial.
When will data be available (start and end dates)?
Immediately following publication of study results with no end date determined.
Available to whom?
Researchers providing a methodologically and ethically sound proposal.
Available for what types of analyses?
Any types of analyses.
How or where can data be obtained?
Data can be obtained by contacting the principal investigator, A/Prof Ben Colagiuri at [email protected].


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
14130Study protocol  [email protected]
14131Statistical analysis plan  [email protected]
14132Analytic code  [email protected]



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 placebo for insomnia (OPIN): Study protocol for a cohort multiple randomised controlled trial.2021https://dx.doi.org/10.1136/bmjopen-2020-044045
N.B. These documents automatically identified may not have been verified by the study sponsor.