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Trial registered on ANZCTR


Registration number
ACTRN12616000017426
Ethics application status
Approved
Date submitted
4/01/2016
Date registered
13/01/2016
Date last updated
17/05/2019
Date data sharing statement initially provided
17/05/2019
Date results information initially provided
17/05/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Managing sleep with Zopiclone in acute low back pain. A feasibility study.
Scientific title
A randomised controlled feasibility study of managing sleep with Zopiclone in participants with acute low back pain and sleep disturbances.
Secondary ID [1] 286945 0
Nil known
Universal Trial Number (UTN)
Trial acronym
SLEEPain
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute mild-moderate Insomnia
 295381 0
Acute low back pain 295382 0
Condition category
Condition code
Musculoskeletal 295641 295641 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is Zopiclone, considered an effective and safe, hypnotic medication with minimal adverse effects and mild chance of abuse, dependence, and tolerance and no withdrawal.
Prior to enrollment each participant will be screened by their GP or a research physician at the Woolcock Institute of Medical Research or Neuroscience Research Australia (NeuRA).
The participant will be required to take the intervention every night for 14 nights.
A standard single dose of 7.5mg will be taken shortly before bedtime for 14 days.
The most commonly reported adverse event is bitter taste. Overall disturbances are rare and mild in intensity, however the participant will be reminded that they can withdraw at any time if they no longer feel comfortable taking the intervention.
The intervention will be given orally in a capsule form.
The participants will be asked to return the empty drug packet to monitor adherence.
Intervention code [1] 292138 0
Treatment: Drugs
Comparator / control treatment
The control group will receive placebo. Placebo is a substance that looks just like the intervention drug Zopiclone but has no therapeutic effect.
It is composed of Avicel, in gelatine capsules.
Control group
Placebo

Outcomes
Primary outcome [1] 295358 0
Mean sleep quality, calculated from 14 nightly measures of the 11-point Numerical Rating Scale of sleep quality from the modified Pittsburgh Sleep Diary (PghSD).

Monk, T.H, Reynolds III, C.F., Kupfer, D.J., Buysse, D.J., Coble, P.A., Hayes, A.J., Machen, M.A, Petrie, S.R., Ritenour, A.M., The Pittsburgh Sleep Diary. J. Sleep Res (1994) 3, 111-120
Timepoint [1] 295358 0
14 nights of the intervention period.

Primary outcome [2] 295359 0
Mean pain intensity measured by Pain Intensity Numerical Rating Scale.

Childs, J. D., Piva, S. R. & Fritz, J. M. Responsiveness of the numeric pain rating scale in patients with low back pain. Spine (Phila. Pa. 1976). 30, 1331–1334 (2005)
Timepoint [2] 295359 0
Average pain assessed at 14 days
Secondary outcome [1] 315406 0
Risk of chronic disability measure by the (Orebro Musculoskeletal Pain Screening Questionnaire (OMPSQ))

Hockings, R. L., McAuley, J. H. & Maher, C. G. A systematic review of the predictive ability of the Orebro Musculoskeletal Pain Questionnaire. Spine (Phila. Pa. 1976). 33, E494–E500 (2008).
Timepoint [1] 315406 0
Assessed at 2 weeks post commencement of intervention and 6 weeks post commencement of intervention.
Secondary outcome [2] 315407 0
Global recovery (The Patient Global Back Recovery Scale (GBRS))

Hush, J. M., Kamper, S. J., Stanton, T. R., Ostelo, R. & Refshauge, K. M. Standardized measurement of recovery from nonspecific back pain. Arch. Phys. Med. Rehabil. 93, 849–855 (2012).
Timepoint [2] 315407 0
This will be completed at baseline, 2 weeks post commencement of intervention and 6 weeks post commencement of intervention.
Secondary outcome [3] 315408 0
Depression and Anxiety (DASS-21)

Ronk, F. R., Korman, J. R., Hooke, G. R. & Page, A. C. Assessing clinical significance of treatment outcomes using the DASS-21. Psychol. Assess. 25, 1103–10 (2013).
Timepoint [3] 315408 0
This will be completed at baseline, 2 weeks post commencement of intervention and 6 weeks post commencement of intervention
Secondary outcome [4] 315409 0
Insomnia (Insomnia Severity Index)

Alsaadi, S. M. et al. Detecting insomnia in patients with low back pain: accuracy of four self-report sleep measures. BMC Musculoskelet Disord 14, 196 (2013).
Timepoint [4] 315409 0
This will be completed at baseline, 2 weeks post commencement of intervention and 6 weeks post commencement of intervention
Secondary outcome [5] 315410 0
Fatigue (The Flinders Fatigue Scale (FFS))

Gradisar, M. et al. The flinders fatigue scale: Preliminary psychometric properties and clinical sensitivity of a new scale for measuring daytime fatigue associated with insomnia. J. Clin. Sleep Med. 3, 722–728 (2007).
Timepoint [5] 315410 0
This will be completed at baseline, 2 weeks post commencement of intervention and 6 weeks post commencement of intervention
Secondary outcome [6] 315411 0
Drowsiness (Epsworth Sleepiness Scale)

Johns, M. W. Reliability and factor analysis of the Epworth Sleepiness Scale. Sleep 15, 376–381 (1992).
Timepoint [6] 315411 0
This will be completed at baseline, 2 weeks post commencement of intervention and 6 weeks post commencement of intervention
Secondary outcome [7] 315412 0
Sleep Effort (The Glasgow Sleep Effort Scale)

Broomfield, N. M. & Espie, C. a. Towards a valid, reliable measure of sleep effort. J. Sleep Res. 14, 401–407 (2005).
Timepoint [7] 315412 0
This will be completed at baseline, 2 weeks post commencement of intervention and 6 weeks post commencement of intervention
Secondary outcome [8] 315413 0
Participant Satisfaction (Participant Satisfaction Questionnaire)
Timepoint [8] 315413 0
This will be completed at 6 weeks post commencement of intervention
Secondary outcome [9] 319818 0
Objective Measure of movement intensity while asleep, using Actiwatch
Timepoint [9] 319818 0
14 nights of the intervention period.
Secondary outcome [10] 319819 0
DynaPort Move Monitor measuring movement and body position during the night
Timepoint [10] 319819 0
the first 7 nights of the intervention period

Eligibility
Key inclusion criteria
1. Low back pain.
2. Mild to moderate insomnia (Insomnia Severity Index score of between 7-21), of less than 6 weeks duration
3. Sufficient understanding of written and verbal English language.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known allergy to sedative drugs
2. Diagnosed with sleep disorder including sleep apnea, primary hypersomnia, narcolepsy, circadian rhythm disorder, parasomnia or dyssomnia.
3. Diagnosed with a psychiatric disorder
4. Diagnosis serious hepatic disorder
5. Diagnosis severe myasthenia gravis
6. Diagnosis acute narrow angle glaucoma
7. Major surgery or blood donation in the past 12 weeks
8. Pregnancy or expected pregnancy, or breastfeeding
9. Have a history of substance abuse or substance dependence subjects with alcohol abuse.
10. Weekly consumption more than 14 units (women) or 21 units (men) of alcohol.
11. Daily consumption of more than the nicotine-equivalent of 15 cigarettes a day.
12. Daily consumption of more than 5 caffeine-containing beverages a day/ caffeine consumption of >500 mg/day
13. Flew >2 time zone in the past month or will have to do so during course of the study
14. Working night shifts and unable or unwilling to discontinue this work pattern
15. Presented with any condition that would prevent normal management of low back pain such as cancer.

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)
Prior to initiation of the study, the Zopiclone and placebo pills will be encapsulated and placed into Webster packs by a compounding pharmacy.
Both Zopiclone and placebo will be formulated such that the pills and packs appear identical.
Each Webster pack, whether Zopiclone or placebo, will be randomly assigned a number from 1-32, based on a computer generated random number sequence. Pack numbering was performed by two independent researchers otherwise uninvolved in the study. The packs will be used in a consecutive manner as participants are enrolled.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A block randomization schedule will be created using computer-generated random number table,
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
Parallel
Other design features
The participants will also be asked to complete a participant satisfaction and devices utility questionnaire.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical analysis will be carried out on an intent-to-treat basis. Group comparisons will be made using ANOVA. The overall survival/ resolution of symptoms rate will be calculated by nonparametric Kaplan-Meier method. The median days to recovery will be calculated. Treatment effects will be represented by point estimates and confidence intervals of all outcome variables at all follow-up points.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
21/12/2015
Date of last participant enrolment
Anticipated
20/09/2017
Actual
17/02/2017
Date of last data collection
Anticipated
Actual
31/03/2017
Sample size
Target
32
Accrual to date
Final
22
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 291505 0
Self funded/Unfunded
Name [1] 291505 0
Not funded
Country [1] 291505 0
Primary sponsor type
Individual
Name
Dr. James McAuley
Address
Neuroscience Research Australia (NeuRA)
PO Box 1165
Randwick
NSW
2031
Country
Australia
Secondary sponsor category [1] 291072 0
None
Name [1] 291072 0
Address [1] 291072 0
Country [1] 291072 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293045 0
Sydney Local Health District
Ethics committee address [1] 293045 0
Research Development Office
RPAH Medical Centre
Suite 210A, 100 Carillon Avenue
NEWTOWN NSW 2042
Ethics committee country [1] 293045 0
Australia
Date submitted for ethics approval [1] 293045 0
23/06/2015
Approval date [1] 293045 0
15/10/2015
Ethics approval number [1] 293045 0
X15-0251

Summary
Brief summary
Aims and research design
The aim of this pilot study is to assess the feasibility of a randomised controlled trial aimed to improve sleep of patients with low back pain, using a hypnotic drug called Zopiclone, which is a currently available drug approved by the Therapeutic Goods Administration.
Methods
In accordance with recommendations for pilot studies this pilot will recruit thirty-two
participants. Participants will have acute low back pain and a co-existing sleep disturbance. Participants will be randomly allocated to one of two study groups of equal sizes. Patients in both groups will be encouraged to continue with their usual care, one group will receive placebo, while the other group also will receive Zopiclone over the course of 14 days.
Procedure
Participants who have sleep apnoea or severe insomnia will be excluded.
As this is a pilot study the primary aim of this study is to use the data obtained to refine recruitment, outcome measures and randomisation procedures for a larger trial. A secondary aim of this study is to estimate the effect of managed sleep on acute low back pain from the 95% confidence intervals. There have been no other studies to date that have evaluated the feasibility of controlling sleep as a way of improving low back pain. As this is a feasibility study the primary outcome measure has not yet been defined. The participants will be asked to complete a Pittsburgh Sleep diary and a numeric rating scale (NRS) to rate their average pain intensity daily for the first 14 days. During this time participants will be asked to wear an actiwatch overnight. The actiwatch measures movement during sleep and therefore it is an indirect measure of sleep quality. Participants will be asked to complete a Low back screening questionnaire and Global perception of change scale. These measures were selected because they are widely employed to assess persistence in low back pain. Psychological factors including depression and anxiety will be measured using the DASS. Participants will also be asked to rate next day effects using a Flinders fatigue scale and an Epsworth sleepiness scale.
Conclusion.
This trial aims to conclude whether or not it is feasible to do a large scale randomised placebo controlled trial.
Trial website
Trial related presentations / publications
None available as yet
Public notes
Attachments [1] 632 632 0 0
/AnzctrAttachments/368790(v10-11-2015-16-23-01)-Protocol 2.docx

Contacts
Principal investigator
Name 58218 0
Dr James McAuley
Address 58218 0
Neuroscience Research Australia (NeuRA)
PO Box 1165
Randwick
NSW
2031
Country 58218 0
Australia
Phone 58218 0
+612 93991266
Fax 58218 0
+612 93991121
Email 58218 0
j.mcauley@neura.edu.au
Contact person for public queries
Name 58219 0
Dr James McAuley
Address 58219 0
Neuroscience Research Australia (NeuRA)
PO Box 1165
Randwick
NSW
2031
Country 58219 0
Australia
Phone 58219 0
+612 93991266
Fax 58219 0
+612 93991121
Email 58219 0
j.mcauley@neura.edu.au
Contact person for scientific queries
Name 58220 0
Dr James McAuley
Address 58220 0
Neuroscience Research Australia (NeuRA)
PO Box 1165
Randwick
NSW
2031
Country 58220 0
Australia
Phone 58220 0
+612 93991266
Fax 58220 0
+612 93991121
Email 58220 0
j.mcauley@neura.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD being made available was not considered at the development of this trial


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.