ANZCTR - Registration

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]

None

Universal Trial Number (UTN)

U1111-1272-1961

Trial acronym

Linked study record

Health condition

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

Knee osteoarthritis

Total knee arthroplasty

Condition category

Condition code

Musculoskeletal

Osteoarthritis

Surgery

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]

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]

Change in numeric pain rating scale (NPRS)

Timepoint [1]

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]

30 second Timed Stands (chair stand) test to assess physical function, dynamic balance and pain

Timepoint [1]

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]

40m fast-paced walk test to assess pain, walking speed over a short distance, and changing direction whilst walking

Timepoint [2]

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]

Timed Up-and-Go test to assess functional mobility, balance and pain

Timepoint [3]

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]

WOMAC knee score to assess pain, stiffness and physical function

Timepoint [4]

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]

Hospital anxiety and depression scale (HADS)

Timepoint [5]

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]

Forgotten Joint Score

Timepoint [6]

Weeks 2, 4 and 6 after surgery
At 6- and 12-months after surgery

Secondary outcome [7]

Knee Injury and Osteoarthritis Outcome Score (KOOS)

Timepoint [7]

At baseline 1 week pre-operatively
At 6 and 12 months after surgery

Secondary outcome [8]

Surgical wound healing

Timepoint [8]

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]

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]

Samples normally removed and discarded at the time of surgery (to accommodate the prosthetic implant) will be collected for analysis.

Secondary outcome [10]

Manual muscle strength test

Timepoint [10]

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]

Knee circumference measured with tape measure (cm)

Timepoint [11]

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]

Joint range of motion (measured with goniometer)

Timepoint [12]

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]

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]

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]

Side effects/Adverse events from study diary

Timepoint [14]

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

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]

Charities/Societies/Foundations

Name [1]

Mater Foundation

Country [1]

Australia

Primary sponsor type

Other Collaborative groups

Name

Mater Misericordiae Limited

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

A/Prof Liisa Laakso

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Mater Misericordiae Limited Human Research Ethics Committee

Ethics committee address [1]

Aubigny Place, Raymond Terrace, South Brisbane Queensland 4101

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

05/10/2021

Approval date [1]

14/01/2022

Ethics approval number [1]

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

Public notes

Contacts

Principal investigator

Name

Dr Liisa Laakso

Address

Mater Research Institute
Aubigny Place
Raymond Terrace, South Brisbane
Queensland 4101

Country

Australia

Phone

+61 0419686134

Email

[email protected]

Contact person for public queries

Name

Liisa Laakso

Address

Mater Research Institute
Aubigny Place
Raymond Terrace, South Brisbane
Queensland 4101

Country

Australia

Phone

+61 0419686134

Email

[email protected]

Contact person for scientific queries

Name

Liisa Laakso

Address

Mater Research Institute
Aubigny Place
Raymond Terrace, South Brisbane
Queensland 4101

Country

Australia

Phone

+61 0419686134

Email

[email protected]

Trial Review

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