ANZCTR - Registration

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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]

None

Universal Trial Number (UTN)

Trial acronym

DREAM

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Sciatica

Condition category

Condition code

Musculoskeletal

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]

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]

Leg pain intensity

Timepoint [1]

Baseline, 4, 8, 12 (primary timepoint), 16, 26 and 52 weeks post-randomisation

Secondary outcome [1]

Disability (key secondary outcome)

Timepoint [1]

Baseline, 4, 8, 12, 16, 26, and 52 weeks post-randomisation

Secondary outcome [2]

Low back pain intensity

Timepoint [2]

Baseline, 4, 8, 12, 16, 26, and 52 weeks post-randomisation

Secondary outcome [3]

Time to recovery

Timepoint [3]

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]

Quality of life

Timepoint [4]

Baseline, 4, 8, 12, 16, 26, and 52 weeks post-randomisation.

Secondary outcome [5]

Depression

Timepoint [5]

Baseline and 8 weeks post-randomisation

Secondary outcome [6]

Anxiety

Timepoint [6]

Baseline and 8 weeks post-randomisation

Secondary outcome [7]

Sleep disturbance

Timepoint [7]

Baseline and 8 weeks post-randomisation

Secondary outcome [8]

Work absenteeism

Timepoint [8]

4, 8, 12, 16, 26, and 52 weeks post-randomisation

Secondary outcome [9]

Global perceived effect

Timepoint [9]

4, 8, 12, 16, 26, and 52 weeks post-randomisation

Secondary outcome [10]

Safety

Timepoint [10]

2, 4, 6, 8, 12, and 16 weeks post-randomisation

Secondary outcome [11]

Adherence to study medication

Timepoint [11]

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?

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]

Government body

Name [1]

National Health and Medical Research Council (NHMRC)

Address [1]

Country [1]

Australia

Primary sponsor type

University

Name

The University of Sydney

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The University of Sydney Human Research Ethics Committee

Ethics committee address [1]

https://www.sydney.edu.au/research/research-integrity-and-ethics.html

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

29/01/2024

Approval date [1]

01/05/2024

Ethics approval number [1]

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

Dr Giovanni Ferreira

Address

Institute for Musculoskeletal Health, The University of Sydney, Level 10N KGV Building, Missensden Road, Camperdown, NSW, 2050

Country

Australia

Phone

+61 02 86276681

Fax

[email protected]

Contact person for public queries

Name

Melissa Webb

Address

Institute for Musculoskeletal Health, The University of Sydney, Level 10N KGV Building, Missensden Road, Camperdown, NSW, 2050

Country

Australia

Phone

+61 02 86276254

Fax

[email protected]

Contact person for scientific queries

Name

Giovanni Ferreira

Address

Institute for Musculoskeletal Health, The University of Sydney, Level 10N KGV Building, Missensden Road, Camperdown, NSW, 2050

Country

Australia

Phone

+61 02 86276681

Fax

[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.	Type	Email
22345	Study protocol	[email protected]
22346	Statistical analysis plan	[email protected]
22347	Ethical approval	[email protected]

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.

Trial Review

Documents added manually

Documents added automatically