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Trial registered on ANZCTR


Registration number
ACTRN12614000719639
Ethics application status
Approved
Date submitted
1/07/2014
Date registered
8/07/2014
Date last updated
20/11/2018
Date data sharing statement initially provided
20/11/2018
Date results information initially provided
20/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Modic trial: do osteoporosis therapies work for back pain?
Scientific title
Effect of zoledronic acid or denosumab on Modic-change related back pain.
Secondary ID [1] 284900 0
Nil
Universal Trial Number (UTN)
Trial acronym
Modic
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Back pain 292358 0
Condition category
Condition code
Musculoskeletal 292681 292681 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Zoledronic acid 5mg in 100ml saline given by intravenous infusion OR denosumab 60mg in 1ml subcutaneous injection.
Participants receive two needles in a double dummy approach, receiving zoledronic acid (IV) and saline placebo (subcutaneous injection) OR saline (IV) and denosumab (subcutaneous injection) OR saline in both IV and subcutaneous injection.
Intervention is only given once.
Intervention code [1] 289716 0
Treatment: Drugs
Comparator / control treatment
Placebo 100ml (saline infusion); placebo 1ml (saline injection).
There are two separate control arms.
Control group
Placebo

Outcomes
Primary outcome [1] 292524 0
Back pain, as assessed using a 100mm visual analog score.
Timepoint [1] 292524 0
6 months
Primary outcome [2] 292525 0
Maximum size of Modic lesion (mm2), as assessed on MRI.
Timepoint [2] 292525 0
6 months
Secondary outcome [1] 309144 0
Size of Modic lesion on an ordinal scale, using the Nordic Modic Consensus Group classification
Timepoint [1] 309144 0
6 months
Secondary outcome [2] 309145 0
Proportion with type 1 Modic changes over 6 months, as assessed on presence or absence of Modic changes visible on MRI.
Timepoint [2] 309145 0
6 months
Secondary outcome [3] 309146 0
Back pain as assessed by questionnaire (the LBP Rating Scale)
Timepoint [3] 309146 0
3 months
Secondary outcome [4] 309147 0
Disability, using the Roland Morris Disability Questionnaire
Timepoint [4] 309147 0
6 months
Secondary outcome [5] 309148 0
Safety assessed by monitoring and reporting any adverse events. Adverse events include any changes in the health of a participant and will be self-reported. Participants will be asked to report any adverse events at 3 months (by questionnaire designed for this purpose) and 6 months (by interview). Participants will also be able to report events between clinic visits by telephoning the coordinator. Adverse events may include, for example, a reaction at the infusion / injection site, attendance at a hospital emergency department, hospitalisation. All adverse events will be reported to the Prinicpal Investigator at each site who will determine the relationship (or otherwise) to zoledronic acid or denosumab.
Timepoint [5] 309148 0
3 and 6 months
Secondary outcome [6] 309150 0
Utility, as assessed by the AQoL questionnaire.
Timepoint [6] 309150 0
6 months

Eligibility
Key inclusion criteria
Back pain primarily due to Modic changes visible on MRI.
Back pain >40 on 100mm VAS.
Aged >40 years.
Modic changes type 1 must be present in at least one vertebrae (L1-L5 or upper endplate of S1).
Participants must be able and willing to provide written informed consent and to comply with the requirements of the study.
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Prior use of bisphosphonates, except according to a washout schedule
Prior use of denosumab
Contra-indications to use of zoledronic acid or denosumab: history of non-traumatic iritis or uveitis, abnormal blood tests [serum calcium >2.75 mmol/L (11.0 mg/dL) or <2.00 mmol/L (8.0 mg/dL) or creatinine < 35 ml/min], serum 25-hydroxyvitamin D concentrations < 40 nmol/L (such participants can receive vitamin D supplementation prior to study entry), particiant is pregnant, breastfeeding, or planning to become pregnant. Female participants who are able to conceive will be required to use adequate contraception.
Use of any investigational drug(s) and/or devices within 30 days prior to randomisation
Prior diagnosis of cancer (metastatic cancer or cancer diagnosed < 2 years ago where treatment is still ongoing)
Poor dental fitness: Persons will be excluded from the study if they have had recent dental injuries (implants / extractions) or are aware of the need for dental work (implants / extractions) in the near future (next 6–12 months) or have poor oral health (eg gum disease).
Regular use of high doses of opiate pain medication (equivalent to oxycontin greater than or equal to 80mg/day)
Diagnosis of chronic widespread pain including fibromyalgia or any other centrally mediated pain phenotype.
Leg pain is of a greater severity than back pain
Prior back surgery
The participant is considered by the investigator, for any reason, to be an unsuitable candidate for the study.

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)
Enrolment of participant by allocation to next random number. Random number generation to allocate drug or placebo performed by researcher not involved in seeing participants or assessing outcomes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomization table created by a computer software (i.e. computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
14/07/2014
Actual
14/11/2014
Date of last participant enrolment
Anticipated
Actual
31/10/2015
Date of last data collection
Anticipated
Actual
30/04/2016
Sample size
Target
90
Accrual to date
Final
103
Recruitment in Australia
Recruitment state(s)
TAS

Funding & Sponsors
Funding source category [1] 289522 0
Charities/Societies/Foundations
Name [1] 289522 0
Tasmanian Community Fund
Country [1] 289522 0
Australia
Funding source category [2] 289548 0
Charities/Societies/Foundations
Name [2] 289548 0
Arthritis Australia
Country [2] 289548 0
Australia
Primary sponsor type
University
Name
University of Tasmania
Address
Menzies Research Institute Tasmania
University of Tasmania
Private Bag 23
Hobart
Tasmania 7001
Country
Australia
Secondary sponsor category [1] 288211 0
None
Name [1] 288211 0
Address [1] 288211 0
Country [1] 288211 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291265 0
Tasmania Health & Medical Human Research Ethics Committee
Ethics committee address [1] 291265 0
Office of Research Services
University of Tasmania
Private Bag 1
Hobart TAS 7001
Ethics committee country [1] 291265 0
Australia
Date submitted for ethics approval [1] 291265 0
Approval date [1] 291265 0
25/06/2014
Ethics approval number [1] 291265 0
H0013961

Summary
Brief summary
This study aims to determine whether zoledronic acid or denosumab are efficacious in reducing back pain and size of Modic lesions in persons with back pain and Modic changes. Primary hypothesis is that either drug will be different to placebo for pain and size of Modic lesion at 6 months. The design is a double-blind placebo-controlled trial. Participants will be randomised to receive zoledronic acid or denosumab or placebo, and will be observed for 6 months.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49434 0
Dr Laura Laslett
Address 49434 0
Menzies Research Institute Tasmania
University of Tasmania
Private Bag 23
HOBART TAS 7001
Country 49434 0
Australia
Phone 49434 0
+61 3 6226 7736
Fax 49434 0
+61 3 6226 7704
Email 49434 0
Laura.Laslett@utas.edu.au
Contact person for public queries
Name 49435 0
Dr Laura Laslett
Address 49435 0
Menzies Research Institute Tasmania
University of Tasmania
Private Bag 23
HOBART TAS 7001
Country 49435 0
Australia
Phone 49435 0
+61 3 6226 7736
Fax 49435 0
+61 3 6226 7704
Email 49435 0
Laura.Laslett@utas.edu.au
Contact person for scientific queries
Name 49436 0
Dr Laura Laslett
Address 49436 0
Menzies Research Institute Tasmania
University of Tasmania
Private Bag 23
HOBART TAS 7001
Country 49436 0
Australia
Phone 49436 0
+61 3 6226 7736
Fax 49436 0
+61 3 6226 7704
Email 49436 0
Laura.Laslett@utas.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
The data that will be generated from this study will not be deposited in a
public repository due to privacy and consent restrictions. De-identified data
can be made available from the corresponding author on reasonable request, subject to a data sharing agreement.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Conference abstractNo Conference presentation at the American College of... [More Details] 366594-(Uploaded-20-11-2018-10-42-38)-Other results publication.pdf

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEffect of Zoledronic Acid and Denosumab in Patients With Low Back Pain and Modic Change: A Proof-of-Principle Trial.2018https://dx.doi.org/10.1002/jbmr.3376
N.B. These documents automatically identified may not have been verified by the study sponsor.