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Trial registered on ANZCTR


Registration number
ACTRN12622000051741
Ethics application status
Approved
Date submitted
3/12/2021
Date registered
17/01/2022
Date last updated
11/01/2023
Date data sharing statement initially provided
17/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The Light Knee Study: The effects of light therapy on post-operative pain and functional mobility in people undergoing knee replacement surgery.
Scientific title
An investigation of the effects of photobiomodulation (PBM) therapy on post-operative pain and functional mobility in people undergoing knee replacement surgery (a randomised, sham-controlled study).
Secondary ID [1] 305967 0
None
Universal Trial Number (UTN)
U1111-1272-1961
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Knee osteoarthritis 324567 0
Total knee arthroplasty 324568 0
Condition category
Condition code
Musculoskeletal 322034 322034 0 0
Osteoarthritis
Surgery 322035 322035 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is photobiomodulation (PBM) or light therapy applied using a novel light patch system.
CareWear is a novel, 3-D printed self-adhesive patch with hundreds of micro-diodes (light emitting diodes are found in many home appliances) that emit specific light frequencies that have been found in other research to reduce inflammation and pain. The CareWear patch is registered in the USA and with the Australian Therapeutic Goods Administration (TGA) for applying light to areas of pain and inflammation. The effectiveness of the light patches will be compared to sham light patches.
Consenting participants will be loaned a CareWear kit and visited at home to be shown how to apply the light patches to the knee to be operated on. Whether in the sham (inactive) group or the active intervention group, the light patch treatment period lasts for 3 weeks commencing the week before the participants' scheduled surgery, and for the two weeks following knee replacement surgery. Regardless of which group participants are randomly assigned to, they will continue to be seen for follow-up appointments, and will be asked to complete all tests and questionnaires, as described.
Participants will be visited at home one week before scheduled surgery, one day before the surgery, and at one week, two weeks, four weeks, and six weeks after knee replacement surgery; and again at 6 months and 12 months after surgery. Participants will also be seen in hospital on Day 4 after surgery when they would normally be expected to be discharged from hospital.
Participants will be shown how to self-apply the patches to standardised positions over the large muscle at the front of the thigh, behind the knee, and above and below the knee at each treatment; and remove the patches following each 30-minute daily treatment. Treatment shall be applied with the participant comfortably seated and the knee extended and supported (e.g., on a lounge or bed) to accommodate the popliteal fossa light patch.
Participants will receive the first treatment one week prior to the scheduled knee replacement surgery and will be instructed on how to apply and care for the device at home (placement, application and removal of the patches) for daily treatments until they are admitted to hospital for surgery. Participants will be provided with contact details and asked to call the researcher if they have any questions or concerns during the home application period.
After the surgery, participants will recommence light patch applications every day (for 1 week) commencing on the day immediately following knee replacement surgery unless their doctor advises otherwise. The researchers will continue to see participants whilst they are in hospital, and once discharged home. During the second week after the surgery, participants will apply the light patches 3 more times, after which the treatment phase of the research is complete. In total there will be 17 treatments of 30 minutes each over the course of the study, for each participant. Participants will be seen a total of 9 times over the 12 months of the study with the first appointment lasting approximately 2 hours, and each subsequent appointment lasting less than one hour. Participants will be contacted by telephone between appointments; and adherence to treatment is recorded on the treatment device (from which the unidentifiable data can be downloaded).
The parameters of the light patches are:
- Pulse Frequency: 33KHz
- Wavelength: Combined 450nm (blue light) and 640nm (red light)
- Peak optical power: 6.75 mW/cm2 (450 nm); 2.25 mW/cm2 (640 nm)
- Pulse duration/interval: 10 microsec/20 microsec
- Radiant exposure (dose): 4.5 J/cm2
Intervention code [1] 322360 0
Treatment: Devices
Comparator / control treatment
The comparator treatment is a sham device designed to look and feel like the active devices. The device will be programmed to behave in the same way as the active devices with tactile (vibration) and visual signals. The sham devices will emit an initial pulse of light briefly at the start of the treatment, and briefly every 1 minute during treatment. No photonic energy will be emitted between these pulses.
Control group
Placebo

Outcomes
Primary outcome [1] 329796 0
Change in numeric pain rating scale (NPRS)
Timepoint [1] 329796 0
Baseline one week prior to knee replacement surgery
One day prior to knee replacement surgery
Day 4 post-operation
1 week post-operation (primary timepoint)
2 weeks post-operation
4 weeks post-operation
6 weeks post-operation
6 months post-operation
12 months post-operation
Secondary outcome [1] 403814 0
30 second Timed Stands (chair stand) test to assess physical function, dynamic balance and pain
Timepoint [1] 403814 0
Baseline one week prior to knee replacement surgery
One day prior to knee replacement surgery
Day 4 post-operation
1 week post-operation
2 weeks post-operation
4 weeks post-operation
6 weeks post-operation
6 months post-operation
12 months post-operation
Secondary outcome [2] 403815 0
40m fast-paced walk test to assess pain, walking speed over a short distance, and changing direction whilst walking
Timepoint [2] 403815 0
Baseline one week prior to knee replacement surgery
One day prior to knee replacement surgery
1 week post-operation
2 weeks post-operation
4 weeks post-operation
6 weeks post-operation
6 months post-operation
12 months post-operation
Secondary outcome [3] 403816 0
Timed Up-and-Go test to assess functional mobility, balance and pain
Timepoint [3] 403816 0
Baseline one week prior to knee replacement surgery
One day prior to knee replacement surgery
Day 4 post-operation
1 week post-operation
2 weeks post-operation
4 weeks post-operation
6 weeks post-operation
6 months post-operation
12 months post-operation
Secondary outcome [4] 403817 0
WOMAC knee score to assess pain, stiffness and physical function
Timepoint [4] 403817 0
Baseline one week prior to knee replacement surgery
One day prior to knee replacement surgery
1 week post-operation
2 weeks post-operation
4 weeks post-operation
6 weeks post-operation
6 months post-operation
12 months post-operation
Secondary outcome [5] 403818 0
Hospital anxiety and depression scale (HADS)
Timepoint [5] 403818 0
Baseline one week prior to knee replacement surgery
One day prior to knee replacement surgery
1 week post-operation
2 weeks post-operation
4 weeks post-operation
6 weeks post-operation
6 months post-operation
12 months post-operation
Secondary outcome [6] 403819 0
Forgotten Joint Score
Timepoint [6] 403819 0
Weeks 2, 4 and 6 after surgery
At 6- and 12-months after surgery
Secondary outcome [7] 403820 0
Knee Injury and Osteoarthritis Outcome Score (KOOS)
Timepoint [7] 403820 0
At baseline 1 week pre-operatively
At 6 and 12 months after surgery
Secondary outcome [8] 403821 0
Surgical wound healing
Timepoint [8] 403821 0
Assessed by blinded assessor from photographs taken at:
Baseline 1 week before surgery
Day 4 post-operation
1 week post-operation
2 weeks post-operation
4 weeks post-operation
Secondary outcome [9] 403828 0
Exploratory analysis of bone, synovial membrane and synovial fluid samples is a composite secondary outcome for investigating:
- inflammatory cytokines (most likely IL-1 and IL-6)
- histology using simple haematoxylin and eosin (H&E) staining for evidence of basic tissue morphology, inflammatory cell infiltrate, fibrosis / necrosis, bone erosion, osteoblasts and osteoclasts, vascularisation, and acid profile of the cytoplasm.

If the initial histologic analysis demonstrates that there are differences between samples exposed to active PBM compared to sham PBM, further analysis will be undertaken depending on what has been noted with histology. Further analyses by immunofluorescence +/- immunohistochemistry staining of samples may include extracellular matrix compounds, cell differentiation, and other target proteins.
Timepoint [9] 403828 0
Samples normally removed and discarded at the time of surgery (to accommodate the prosthetic implant) will be collected for analysis.
Secondary outcome [10] 403829 0
Manual muscle strength test
Timepoint [10] 403829 0
Baseline one week prior to knee replacement surgery
One day prior to knee replacement surgery
1 week post-operation
2 weeks post-operation
4 weeks post-operation
6 weeks post-operation
6 months post-operation
12 months post-operation
Secondary outcome [11] 403830 0
Knee circumference measured with tape measure (cm)
Timepoint [11] 403830 0
Baseline one week prior to knee replacement surgery
Day 4 post-operation
1 week post-operation
2 weeks post-operation
4 weeks post-operation
6 weeks post-operation
6 months post-operation
12 months post-operation
Secondary outcome [12] 403831 0
Joint range of motion (measured with goniometer)
Timepoint [12] 403831 0
Baseline one week prior to knee replacement surgery
One day prior to knee replacement surgery
Day 4 post-operation
1 week post-operation
2 weeks post-operation
4 weeks post-operation
6 weeks post-operation
6 months post-operation
12 months post-operation
Secondary outcome [13] 403832 0
Analgesic use (for morphine equivalency):
- during at home period, patients will record analgesic use in a study diary
- during hospital in-patient period, morphine-equivalent concentrations will be extracted and recorded from the participant’s medical record
Timepoint [13] 403832 0
Baseline one week prior to knee replacement surgery
One day prior to knee replacement surgery
Day 4 post-operation
1 week post-operation
2 weeks post-operation
4 weeks post-operation
6 weeks post-operation
6 months post-operation
12 months post-operation
Secondary outcome [14] 403833 0
Side effects/Adverse events from study diary
Timepoint [14] 403833 0
One day prior to knee replacement surgery
Day 4 post-operation
1 week post-operation
2 weeks post-operation
4 weeks post-operation
6 weeks post-operation
6 months post-operation
12 months post-operation

Eligibility
Key inclusion criteria
Males and females between 60 and 87 years old and fit for surgery
Undergoing unilateral total knee replacement surgery for severe osteoarthritis at the Mater Hospital Brisbane or Mater Private Hospital Brisbane
Minimum age
60 Years
Maximum age
87 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Coagulopathy
Pre-existing pain syndrome such as peripheral neuropathy
Previous history of stroke
Previous surgery/severe trauma of the operated knee
Neuromuscular disease significantly affecting the operated knee
Severe back pain and arthritis significantly affecting mobility or referring pain to the operated leg
Significant cognitive dysfunction that may prevent ability to consent to participation in the study (people of a non-English speaking background will NOT be excluded if a reliable interpreter will be available to assist with explaining the study requirements, taking part in outcome questionnaires etc)
Medical diagnosis of significant mental ill health (e.g., severe depression, anxiety, catastrophising etc) which may impact upon recovery period
Photosensitising agents (drugs)
Tumour at the knee or thigh where patches will be applied
Skin sensitivity to medical adhesives

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)
Allocation concealment by sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
2-4-6 random-permuted block randomization
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
As all modelling involves correlated outcomes (whether by protocol-level clustering or within-patient correlation), we will employ mixed modelling for all analysis. As primary endpoint (pain scores compared between baseline and each subsequent NPRS assessment) is a binary variable, we will use binary logistic mixed-effect regression. The primary and the secondary outcome variables all represent longitudinal measurements from quantitative psychometric or clinimetric scales. Consequently, Linear Mixed Modelling will be employed. The primary analysis will utilize the Intention-to-treat analysis set, but the per-protocol set may also be used to gauge effectiveness of the therapy (patient compliance is being measured). All analysis will be conducted using the R statistics package [https://www.R-project.org/], and mixed-effect modelling using the R library. For all dataset comparisons, a p value of <0.05 will be considered statistically significant.

As the primary outcome in this study is both continuous and measured longitudinally, we have employed the sample size calculation suggested by Diggle et al (2002). Assuming a significance level of 0.05, 80% power, a moderately strong within-subject correlation (p=0.6), a within-standard deviation of 2.1 (based on a study by Langella et al, 2018) and an anticipated drop-out rate of 20%, 60 patients would be required to detect a 2-point difference in pain levels.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
8/02/2022
Actual
9/06/2022
Date of last participant enrolment
Anticipated
29/09/2023
Actual
Date of last data collection
Anticipated
27/09/2024
Actual
Sample size
Target
60
Accrual to date
18
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 310308 0
Charities/Societies/Foundations
Name [1] 310308 0
Mater Foundation
Country [1] 310308 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Mater Misericordiae Limited
Address
Raymond Terrace , South Brisbane, Queensland 4101
Country
Australia
Secondary sponsor category [1] 311429 0
Individual
Name [1] 311429 0
A/Prof Liisa Laakso
Address [1] 311429 0
Mater Research
Aubigny Place, Raymond Terrace, South Brisbane Queensland 4101
Country [1] 311429 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309972 0
Mater Misericordiae Limited Human Research Ethics Committee
Ethics committee address [1] 309972 0
Aubigny Place, Raymond Terrace, South Brisbane Queensland 4101
Ethics committee country [1] 309972 0
Australia
Date submitted for ethics approval [1] 309972 0
05/10/2021
Approval date [1] 309972 0
14/01/2022
Ethics approval number [1] 309972 0
HREC/MML/79175 (V4)

Summary
Brief summary
In this study (called a randomised, sham-controlled clinical trial) we want to find out if the application of an innovative new adhesive light patch can reduce pain and improve recovery of movement after knee replacement surgery. In this study, we will compare the effect of the active device with the inactive (sham) device. Half of the participants will receive the active treatment, and half will receive the sham treatment.

Today, the usual approach to pain relief and movement recovery after knee replacement surgery is a combination of pain-relief drugs (analgesics) and exercise rehabilitation. They work well, but some people continue to have pain after knee replacement for up to 6 or even 12 months; and they may require continued need for pain medications.

We have previously carried out a small feasibility study to work out the protocol details for this new research study. In the feasibility study, we found that patients accepted and tolerated the device, that it was easy for patients to apply at home, and the device provided good pain relief both before and after knee replacement surgery and good recovery of physical movement after the surgery. Based on our previous research, we expect that using a low dose of light therapy daily before knee replacement surgery, and daily after the surgery for one week after surgery, may help people to have less pain in the days following surgery. We also think that further treatment in the second week after surgery will aid recovery of movement and reduce pain in the weeks and months following the operation.

The device we are testing is called CareWear. CareWear is a novel, 3-D printed self-adhesive patch with hundreds of micro-diodes (light emitting diodes are found in many home appliances) that emit specific light frequencies that have been found in other research to reduce inflammation and pain. The CareWear patch is registered in the USA and with the Australian Therapeutic Goods Administration (TGA) for applying light to areas of pain and inflammation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 116030 0
Dr Liisa Laakso
Address 116030 0
Mater Research Institute
Aubigny Place
Raymond Terrace, South Brisbane
Queensland 4101
Country 116030 0
Australia
Phone 116030 0
+61 0419686134
Fax 116030 0
Email 116030 0
[email protected]
Contact person for public queries
Name 116031 0
Liisa Laakso
Address 116031 0
Mater Research Institute
Aubigny Place
Raymond Terrace, South Brisbane
Queensland 4101
Country 116031 0
Australia
Phone 116031 0
+61 0419686134
Fax 116031 0
Email 116031 0
[email protected]
Contact person for scientific queries
Name 116032 0
Liisa Laakso
Address 116032 0
Mater Research Institute
Aubigny Place
Raymond Terrace, South Brisbane
Queensland 4101
Country 116032 0
Australia
Phone 116032 0
+61 0419686134
Fax 116032 0
Email 116032 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The data will continue to be used for the purposes of R&D thus not able to be shared.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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No additional documents have been identified.