Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001694808
Ethics application status
Approved
Date submitted
18/11/2020
Date registered
10/12/2021
Date last updated
11/11/2022
Date data sharing statement initially provided
10/12/2021
Date results information initially provided
11/11/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of low-level and high-intensity laser therapy as an adjunct to rehabilitation exercise in the management of adults with mild to moderate knee osteoarthritis.
Scientific title
Short- and long-term effects of low-level and high-intensity laser therapy as an adjunct to rehabilitation exercise on clinical outcomes among adults with mild to moderate knee osteoarthritis: a randomized control trial
Secondary ID [1] 302813 0
None
Universal Trial Number (UTN)
U1111-1261-3064
Trial acronym
LT (Laser Therapy Trial)
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
knee osteoarthritis 319772 0
Condition category
Condition code
Physical Medicine / Rehabilitation 317705 317705 0 0
Other physical medicine / rehabilitation
Musculoskeletal 322100 322100 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The recruited participants (n = 60) will be allocated into three equal-size groups by simple block randomization based on age and gender; Group 1 (Low-level laser therapy + Exercise), Group 2 (High-intensity laser therapy + Exercise), and Group 3 (Placebo laser + Exercise). All participants will receive their usual physiotherapy care provided by the Sports Medicine Unit of the University Malaya Medical Centre (UMMC). The usual physiotherapy care is a rehabilitation exercise program that is individually tailored to the participant's needs and will be prescribed and progressed based on recommended knee osteoarthritis (KOA) treatment guidelines (to ensure uniformity in rehabilitation programs). This exercise program will take approximately one hour per session, and examples of the exercises are active movement exercises, stretching, flexibility, muscle strengthening, knee stabilization exercise, and functional training. The usual physiotherapy treatment will be administered by qualified physiotherapists from the Sports Medicine Unit (UMMC) who are unaware of participants’ grouping.

In addition to the usual rehabilitation, participants in the Group 1 (LLLT+E, n = 20) and Group 2 (HILT+E, n = 20) will receive an active application of LLLT and HILT, respectively. Interventions will be conducted twice a week for a consecutive six weeks, and the laser interventions will be carried out by the same physiotherapist who will not involve in the outcome’s assessment. A regular phone call reminder and attendance checklist will be used to monitor participants' adherence to the intervention program. Details of the interventions for Group 1 and 2 are as follows:

Group 1 LLLT+E (n = 20)
Low-level laser therapy (LLLT) in addition to usual physiotherapy care, twice a week for six weeks; laser model GA diode (BTL), wavelength 830 nm, energy density 50 Jcm2, total energy 1250 Joule per session, 15 minutes of laser treatment per session (5 minutes of analgesic mode and 10 minutes of biostimulation mode), and the laser treatment will be applied at the medial and lateral knee joint lines.

Group 2 HILT+E (n = 20)
High-intensity laser therapy (HILT) in addition to usual physiotherapy care, twice a week for six weeks; laser model GA diode (BTL-5000 laser), wavelength 1064 nm, energy density 100 Jcm2, total energy 2400 Joule per session, 15 minutes of laser treatment per session (5 minutes of analgesic mode and 10 minutes of biostimulation mode), and the laser treatment will be applied at the medial and lateral knee joint lines.
Intervention code [1] 319087 0
Rehabilitation
Intervention code [2] 319088 0
Treatment: Devices
Comparator / control treatment
Group 3: PL+E (n = 20)
Placebo laser in addition to usual physiotherapy care, twice a week for eight weeks. The procedures would be identical to the actual laser application but without emission of energy (15 minutes of laser treatment per session and will be applied at the medial and lateral knee joint lines).
Control group
Placebo

Outcomes
Primary outcome [1] 325756 0
The Knee Injury and Osteoarthritis Outcome Score (KOOS) is a self-administered questionnaire to evaluate participants’ views about their knee and associated problems with osteoarthritis (OA). The questionnaire consists of 42 items across five subscales which will be scored independently; (1) knee pain during functional activities; (2) symptoms such as knee stiffness, swelling and active knee joint range; (3) activities of daily living; (4) sport and recreational activities; and (5) quality of life.
Timepoint [1] 325756 0
The outcomes measures will be evaluated at four different intervals; (1) pre-intervention at week-0, (2) mid-intervention at week-3, (3) post-intervention at week-6, and (4) follow-up at week-18. The primary timepoints will be pre-(week-0) and post-intervention (week-6).
Secondary outcome [1] 389015 0
Numerical Rating Pain Scale (NRPS). It is a common measure of pain intensity in clinical practice. It is a subjective measure in which individuals evaluate their pain on an eleven-point numerical scale, with the scores ranged from 0 (no pain at all) to 10 (worst imaginable pain).
Timepoint [1] 389015 0
The outcomes measures will be evaluated at four different intervals; (1) pre-intervention at week-0, (2) mid-intervention at week-3, (3) post-intervention at week-6, and (4) follow-up at week-18.
Secondary outcome [2] 389016 0
Time Up and Go (TUG): TUG test is a highly reliable, valid, cost-effective, and time-efficient method to evaluate overall functional mobility, balance and risk for falls. The participants will be asked to sit on an armchair with the height is 46 cm. They need to rise form the chair and walk at a safe and comfortable pace to a mark 3 m away, which is mark by a line and a cone. They need to turn around the cone then return to a sitting position in the chair. They are allowed to use walking aids while walking and hold the armrest to sit and stand. The time will be recorded as the participant start to move from the chair and sit back on the chair, and a score of more than 14 seconds indicated a high risk of falls.
Timepoint [2] 389016 0
The outcomes measures will be evaluated at four different intervals; (1) pre-intervention at week-0, (2) mid-intervention at week-3, (3) post-intervention at week-6, and (4) follow-up at week-18.
Secondary outcome [3] 389018 0
Lower Extremity Isokinetic Muscle Performance Assessment: Isokinetic assessment of the knee muscles will be performed by using a computerised isokinetic dynamometer (Norm model, Cybex International, USA). The isokinetic exercise machine is a reliable and feasible tool to assess muscular performance, particularly strength and endurance.
Timepoint [3] 389018 0
The outcomes measures will be evaluated at two different intervals; (1) pre-intervention at week-0, and (2) post-intervention at week-6,

Eligibility
Key inclusion criteria
The inclusion criteria will be: (1) adults of both genders aged 18 to 75 years, (2) diagnosed with symptomatic (pain and/or stiffness) unilateral or bilateral knee osteoarthritis based on the American College of Rheumatology criteria (Nazari et al., 2019), (3) persistent knee pain with intensity at least 3 on a 10-cm visual analog scale (VAS) for more than 3 months during activities such as going up-and downstairs, sitting or squatting (Alayat et al., 2017, Nazari et al., 2019), (4) degenerative osteoarthritic knee of grade 2 (mild) to 3 (moderate) or less according to the Kellgren-Lawrence classification; verified by knee radiograph performed during the last 6 months (Kheshie et al., 2014).

For bilateral knee osteoarthritis, the most painful knee based on pain score will be taken for evaluation; whereas, if findings were identical, the dominant side of the knee would be included (Yurtkuran et al., 2007, Kheshie et al., 2014)
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The exclusion criteria will be as follows: (1) severe knee osteoarthritis (grade 4) according to the Kellgren-Lawrence classification, (2) other pathological conditions such as rheumatic disease, previous hip or knee joint replacement, congenital dysplasia, osteochondritis dissecans, intra-articular fractures, septic arthritis, Perthes disease, ligament or meniscus injury and plica syndrome, (3) history of acute traumatic injuries to the knee or lower extremities (Nazari et al., 2019), (4) patients who had received intra-articular injections (e.g., corticosteroid, hyaluronic acid, or blood-derived products) for knee osteoarthritis during the last 6 months (Kheshie et al., 2014, Alayat et al., 2017, Nazari et al., 2019), (5) uncontrolled medical conditions (e.g., heart, blood, or respiratory disease) that would limit participation with the assessments and intervention program (Alayat et al., 2017), and (6) current participation in another knee osteoarthritis-related interventional 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)
The group allocation will be concealed using central randomization by computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The recruited participants (n = 60) will be allocated into three equal-size groups by simple block randomization stratified by age and gender using a randomization table created by computer software (i.e. computerized sequence generation).
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
Efficacy
Statistical methods / analysis
The data collected will be analyzed using Statistic Product for Statistical Solutions (SPSS) version 23.0 (SPSS Inc. Chicago, USA). Descriptive statistics will be used to describe the demographic information of the participants; age, gender, body mass index, affected side of the knee, severity based on Kellgren-Lawrence grading classification, and duration of KOA. ANCOVA and Chi-Square tests will be applied to analyze the effects of these demographic factors as dependent variables. The primary and secondary outcomes will be assessed using a two-way (3 × 3) ANOVA design with repeated measures to examine the likely interaction between groups (LLLT+E, HILT+E and PL+E) and the time (pre-mid-post eight weeks of intervention, and follow up). Bonferroni’s multiple comparisons test will be performed to determine pairwise differences; mean difference (MD) with a 95% confidence interval (CI). All statistical significances will be set at p < 0.05, and the standardized effect size (ES) will be included to support relevant findings. The ES of each variable will be examined using Cohen’s d for between-groups differences (0.2, 0.5, and 0.8 as small, medium, and large effects, respectively).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/01/2022
Actual
15/01/2022
Date of last participant enrolment
Anticipated
30/06/2022
Actual
10/08/2022
Date of last data collection
Anticipated
31/10/2022
Actual
31/10/2022
Sample size
Target
60
Accrual to date
Final
60
Recruitment outside Australia
Country [1] 23109 0
Malaysia
State/province [1] 23109 0
Kuala Lumpur

Funding & Sponsors
Funding source category [1] 307238 0
Self funded/Unfunded
Name [1] 307238 0
Dr Ashril Yusof
Country [1] 307238 0
Malaysia
Primary sponsor type
Commercial sector/Industry
Name
BTL Industries Malaysia Sdn Bhd
Address
BTL Industries Malaysia Sdn Bhd, Oasis Square, D-1-02,Capital 4, No 2, Jalan PJU 1A/7A, Ara Damansara, 47301 Petaling Jaya, Selangor
Country
Malaysia
Secondary sponsor category [1] 307851 0
None
Name [1] 307851 0
Address [1] 307851 0
Country [1] 307851 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307335 0
Medical Research Ethics Committee, University of Malaya Medical Centre (MREC, UMMC)
Ethics committee address [1] 307335 0
Pusat Perubatan Universiti Malaya,
Lembah Pantai, 59100,
Kuala Lumpur
Ethics committee country [1] 307335 0
Malaysia
Date submitted for ethics approval [1] 307335 0
01/10/2020
Approval date [1] 307335 0
21/12/2020
Ethics approval number [1] 307335 0
MREC ID 2020102-9129

Summary
Brief summary
As a disease-modifying intervention for knee osteoarthritis (KOA) is still unknown, rehabilitation exercise has been frequently combined with physical modalities, and among the recent is low-level (LLLT) and high-intensity laser therapy (HILT). However, it is uncertain which combination is more efficient. Moreover, available treatment guidelines have yet to include LLLT or HILT due to a lack of supporting evidence. Hence, this study aimed to investigate the effects of LLLT versus HILT as an adjunct to rehabilitation exercise on clinical outcomes in KOA.

This study will be a randomized placebo-control design and will adhere to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. This study will involve 60 adults aged between 18 to 75 years with mild to moderate KOA which will be recruited from the Sports Medicine Unit, Department of Rehabilitation Medicine, and Department of Primary Care Medicine (UMMC). The inclusion criteria will be : (i) diagnosed with symptomatic (pain and/or stiffness) KOA based on American College of Rheumatology criteria; and (ii) Kellgren-Lawrence classification of grade 3 (moderate) or less according to knee radiograph.

Participants will be randomly allocated into three equal-size groups; LLLT+E, HILT+E and PL+E. In addition to their usual rehabilitation, LLLT+E (n = 20) and HILT+E (n = 20) groups will receive an active application of LLLT and HILT, respectively. Whereas, PL+E (n = 20) group will be given a placebo laser in addition to their usual rehabilitation. Interventions will be conducted twice a week for six weeks. The outcomes measures (questionaries and physical performance tests) will be evaluated at four different intervals; pre-mid-post intervention, and follow-up at week-18.
Trial website
Trial related presentations / publications
Public notes
This study will provide necessary input as well as a clearer understanding of the short- and long-term effects of laser therapy (especially HILT) combined with rehabilitation exercise on pain, function, and disability levels with a specific focus on adults with mild knee osteoarthritis (KOA). This information may assist related health professionals, particularly physiotherapists, in selecting the most appropriate physical modality to provide the most optimal outcomes. Based on the scientific theory and clinical evidence behind laser treatment, it is anticipated to bring about positive changes in KOA symptoms, subsequently augmenting the effects of primary rehabilitation exercise; ultimately improving health outcomes, as well as decreasing healthcare utilization and burden. Furthermore, this study will provide comprehensive information with quantification of the knee muscles strength in adults with mild KOA, which can be used as a preliminary reference for rehabilitation purpose. Cumulatively, the expected findings may (i) provide a valid justification for HILT to be included as part of mainstream KOA management, and (ii) contribute to the development of a more specific and effective rehabilitation strategy (by integrating laser technology and exercise), particularly in preventing disease progression for patients with mild to moderate KOA.

Contacts
Principal investigator
Name 106874 0
Dr Ashril Yusof
Address 106874 0
Centre for Sports and Exercise Sciences, University of Malaya,
50603, Kuala Lumpur
Country 106874 0
Malaysia
Phone 106874 0
+60379674624
Fax 106874 0
Email 106874 0
[email protected]
Contact person for public queries
Name 106875 0
Mr Mohd Azzuan Ahmad
Address 106875 0
Physiotherapy Programme, Centre for Rehabilitation and Special Needs Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 50300, Kuala Lumpur
Country 106875 0
Malaysia
Phone 106875 0
+60123297292
Fax 106875 0
Email 106875 0
[email protected]
Contact person for scientific queries
Name 106876 0
A/Prof Mohamad Shariff A Hamid
Address 106876 0
Sports Medicine Unit, Faculty of Medicine, University of Malaya Medical Centre, 59100 Kuala Lumpur, Malaysia
Country 106876 0
Malaysia
Phone 106876 0
+60379674968
Fax 106876 0
+60379677511
Email 106876 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


What supporting documents are/will be available?

No Supporting Document Provided



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.