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Trial registered on ANZCTR


Registration number
ACTRN12624000919516
Ethics application status
Approved
Date submitted
19/06/2024
Date registered
29/07/2024
Date last updated
29/07/2024
Date data sharing statement initially provided
29/07/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Duloxetine for chronic sciatica (DREAM): an adaptive randomised placebo-controlled trial
Scientific title
DREAM: an adaptive randomised placebo-controlled trial of duloxetine compared to placebo for reducing leg pain in people with chronic sciatica
Secondary ID [1] 312091 0
None
Universal Trial Number (UTN)
Trial acronym
DREAM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sciatica 333723 0
Condition category
Condition code
Musculoskeletal 330405 330405 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Duloxetine in addition to usual care

Participants randomised to the active arm of the study will receive a 12-week course of oral duloxetine followed by a 2-week tapering phase. The starting dose will be 30 mg/day for 1 week (one 30 mg capsule per day), increasing to 60 mg/day for 11 weeks (maintenance phase – two 30 mg capsules per day). In the 2-week tapering phase, they will receive 30 mg/day (one 30 mg capsule per day) for 2 weeks before treatment is discontinued. Study doctors will be allowed to make modifications to the treatment regimen if required.

Participants in this group will also receive guideline-recommended advice (eg NICE).

Adherence to study medication will be measured by participants’ self-report of daily medication intake, recorded in a diary or online, and by counting the returned medications, against the study doctor’s prescription record.
Intervention code [1] 328532 0
Treatment: Drugs
Comparator / control treatment
Placebo in addition to usual care

The treatment regimen for participants randomised to the placebo arm of the study will be the same as the treatment regimen described for the group receiving duloxetine. The placebo capsules will be identical in appearance to the duloxetine capsules. They will consist of gelatin capsules filled with microcrystalline cellulose.

Participants will also receive guideline-recommended advice as per the intervention arm (eg NICE).
Control group
Placebo

Outcomes
Primary outcome [1] 338158 0
Leg pain intensity
Timepoint [1] 338158 0
Baseline, 4, 8, 12 (primary timepoint), 16, 26 and 52 weeks post-randomisation
Secondary outcome [1] 434761 0
Disability (key secondary outcome)
Timepoint [1] 434761 0
Baseline, 4, 8, 12, 16, 26, and 52 weeks post-randomisation
Secondary outcome [2] 434762 0
Low back pain intensity
Timepoint [2] 434762 0
Baseline, 4, 8, 12, 16, 26, and 52 weeks post-randomisation
Secondary outcome [3] 434763 0
Time to recovery
Timepoint [3] 434763 0
Participants will be asked to record the average daily leg pain intensity score in a pain diary for the duration of treatment (14 weeks) using a 0-10 numerical rating scale. Recovery is defined as seven consecutive days with leg pain intensity no higher than 1 out of 10. Data will be censored at 14 weeks or if participants report having recovered, whichever occurs first.
Secondary outcome [4] 434764 0
Quality of life
Timepoint [4] 434764 0
Baseline, 4, 8, 12, 16, 26, and 52 weeks post-randomisation.
Secondary outcome [5] 434765 0
Depression
Timepoint [5] 434765 0
Baseline and 8 weeks post-randomisation
Secondary outcome [6] 434766 0
Anxiety
Timepoint [6] 434766 0
Baseline and 8 weeks post-randomisation
Secondary outcome [7] 434767 0
Sleep disturbance
Timepoint [7] 434767 0
Baseline and 8 weeks post-randomisation
Secondary outcome [8] 434768 0
Work absenteeism
Timepoint [8] 434768 0
4, 8, 12, 16, 26, and 52 weeks post-randomisation
Secondary outcome [9] 434769 0
Global perceived effect
Timepoint [9] 434769 0
4, 8, 12, 16, 26, and 52 weeks post-randomisation
Secondary outcome [10] 434770 0
Safety
Timepoint [10] 434770 0
2, 4, 6, 8, 12, and 16 weeks post-randomisation
Secondary outcome [11] 434771 0
Adherence to study medication
Timepoint [11] 434771 0
End of treatment phase (14 weeks)

Eligibility
Key inclusion criteria
- Adults (18 years old and above) with radiating pain into one leg in a dermatomal distribution
- Leg pain duration of at least three months
- Evidence of nerve root involvement, defined by the presence of at least ONE of the following clinical signs in the corresponding distribution: myotomal weakness and/or diminished reflex and/or sensory deficit and/or imaging evidence of nerve root impingement that is consistent with the clinical presentation.
- Leg pain that is at least moderate in intensity at the time of enrolment by a study doctor (as measured by a modified version of item 21 in the 36-Item Short Form Survey Instrument).
- An adequate understanding of English or the availability of interpretation services for the participant to complete the trial.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known or suspected specific pathologies in the spine (e.g. fracture, cauda equina syndrome).
- Known or suspected malignancy.
- Having had spinal surgery or other interventional procedure (e.g. epidural injection) in the preceding 6 months.
- Scheduled to have a spinal procedure (e.g. spinal surgery, epidural injection) within 12 weeks at the time of enrolment.
- Currently using any antidepressant for any condition.
- Contraindications to duloxetine, including concomitant use of monoamine oxidase inhibitors, or if a monoamine oxidase inhibitor has been discontinued within less than 2 weeks, known acute or chronic liver disease, concomitant use with CYP1A2 inhibitors (e.g. fluvoxamine).
- Known history of chronic kidney disease stage 4 or above.
- Precautions for use of duloxetine as specified by the Product Information where risks outweigh potential benefits (e.g. depressive symptoms for which treatment is required as judged by the study doctor, bipolar disorder, history of seizure disorder, etc.).
- Previous severe adverse reaction to duloxetine (e.g. serotonin syndrome) as judged by the study doctor
- For females: pregnant, breastfeeding, or planning conception during the treatment period.

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)
Study medication packs will be prepared by a clinical trials investigational product manufacturer according to the randomisation sequence prepared by an independent statistician. Study medication packs will be sealed and distributed to participating sites or dispensed directly to participants. Participants will be dispensed the next sequentially numbered medication pack.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
An independent statistician not involved in any aspect of the study will prepare the randomisation sequence using a computerised random number generator a priori. Patients will be randomised to receive either duloxetine or placebo at a 1:1 ratio using randomly permuted blocks of various sizes.
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
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2024
Actual
Date of last participant enrolment
Anticipated
30/06/2027
Actual
Date of last data collection
Anticipated
30/06/2028
Actual
Sample size
Target
332
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 316448 0
Government body
Name [1] 316448 0
National Health and Medical Research Council (NHMRC)
Country [1] 316448 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Country
Australia
Secondary sponsor category [1] 318624 0
None
Name [1] 318624 0
Address [1] 318624 0
Country [1] 318624 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315239 0
The University of Sydney Human Research Ethics Committee
Ethics committee address [1] 315239 0
https://www.sydney.edu.au/research/research-integrity-and-ethics.html
Ethics committee country [1] 315239 0
Australia
Date submitted for ethics approval [1] 315239 0
29/01/2024
Approval date [1] 315239 0
01/05/2024
Ethics approval number [1] 315239 0
2024/HE000160

Summary
Brief summary
Sciatica affects many Australians every year, and half of the people who develop sciatica report having persisting pain of at least moderate intensity after 1 year. There are no simple, readily available treatments for patients with chronic sciatica. Identifying a simple low-cost treatment for chronic sciatica would be a major advance in the field. We have shown that the antidepressant duloxetine is a promising, accessible, low-cost treatment for chronic sciatica. However, the is considerable uncertainty about its efficacy. We will conduct the DREAM trial, which will provide a definitive answer about the efficacy duloxetine for chronic sciatica.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 134098 0
Dr Giovanni Ferreira
Address 134098 0
Institute for Musculoskeletal Health, The University of Sydney, Level 10N KGV Building, Missensden Road, Camperdown, NSW, 2050
Country 134098 0
Australia
Phone 134098 0
+61 02 86276681
Fax 134098 0
Email 134098 0
[email protected]
Contact person for public queries
Name 134099 0
Melissa Webb
Address 134099 0
Institute for Musculoskeletal Health, The University of Sydney, Level 10N KGV Building, Missensden Road, Camperdown, NSW, 2050
Country 134099 0
Australia
Phone 134099 0
+61 02 86276254
Fax 134099 0
Email 134099 0
[email protected]
Contact person for scientific queries
Name 134100 0
Giovanni Ferreira
Address 134100 0
Institute for Musculoskeletal Health, The University of Sydney, Level 10N KGV Building, Missensden Road, Camperdown, NSW, 2050
Country 134100 0
Australia
Phone 134100 0
+61 02 86276681
Fax 134100 0
Email 134100 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 trial collected as part of the clinical trial will be made available upon request.
When will data be available (start and end dates)?
Data will be made available after the full trial report has been published.
Available to whom?
Data will be available to researchers who provide a methodologically sound proposal for its use and have ethical approval, and will be based on a case-by-case as decided by the Steering Committee.
Available for what types of analyses?
Any
How or where can data be obtained?
Access subject to approvals by the Steering Committee. Please forward any requests to the Principal Investigator, Dr Giovanni Ferreira ([email protected])


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
22345Study protocol  [email protected]
22346Statistical analysis plan  [email protected]
22347Ethical approval  [email protected]



Results publications and other study-related documents

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