Inflammatory Targeted Laser Treatment of Knee Osteoarthritis

Study Overview
=================
Brief Summary
-----------------
This study is conducted to evaluate the effectiveness of low-level laser therapy (LLLT) as an adjunct to exercise therapy in knee osteoarthritis (KOA).

Official Title
-----------------
Inflammatory Targeted Low-level Laser Treatment of Knee Osteoarthritis - A Randomized Clinical Trial

Conditions
-----------------
Knee Osteoarthritis

Intervention / Treatment
-----------------
* Other: Exercise therapy
* Other: LLLT
* Other: Sham LLLT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Any gender Age ≥ 50 years Pain on movement ≥ 40 mm Visual Analog Scale Knee pain for the last ≥ 3 months KOA verified with the American College of Rheumatology criteria using a history and physical examination, i.e. knee pain and at least three of the following: ≥ 50 years old, ≤ 30 minutes of morning stiffness, crepitus on active range of motion, bony tenderness, bony enlargement, and no palpable warmth of synovia Exclusion criteria: Knee alloplastic Total meniscectomy Intra-articular steroid injection and/or oral steroid treatment within the last six months Cancer Rheumatoid arthritis Severe cognitive deficit Neurological deficits affecting the knee Inability to speak and understand English/Norwegian

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Exercise therapy + LLLT<br>Exercise therapy 3 times per week for 8 weeks from baseline. LLLT applied to the knee 3 times per week for 3 weeks from baseline. | Other: Exercise therapy<br>* 5 min. warm up with light exercises for the lower limb prior to strength/endurance exercise therapy. Strength/endurance exercise therapy including level 1 or 2 per session: Level 1: Pelvic lifts (2x15 rep.), one-legged knee bends (2x10 rep. per leg), hip abductions (2x10 rep. per leg). The participants may progress from level 1 to level 2. Level 2: Pelvic lifts (3x15 rep.), one-legged knee bends (3x10 rep. per leg), hip abductions (2x10 rep. per leg), sideways slide (2x10 rep. per leg), and backwards slide (2x10 rep. per leg). The participants may regress from level 2 to level 1.<br>Other: LLLT<br>* - LLLT (60 mW mean output per probe, 904 nm wavelength) applied to the knee in adherence with the recommendations by World Association for Laser Therapy, in terms of dosage per treatment spot.<br>|
| Placebo Comparator: Exercise therapy + sham LLLT<br>Exercise therapy 3 times per week for 8 weeks from baseline. Sham LLLT applied to the knee 3 times per week for 3 weeks from baseline. | Other: Exercise therapy<br>* 5 min. warm up with light exercises for the lower limb prior to strength/endurance exercise therapy. Strength/endurance exercise therapy including level 1 or 2 per session: Level 1: Pelvic lifts (2x15 rep.), one-legged knee bends (2x10 rep. per leg), hip abductions (2x10 rep. per leg). The participants may progress from level 1 to level 2. Level 2: Pelvic lifts (3x15 rep.), one-legged knee bends (3x10 rep. per leg), hip abductions (2x10 rep. per leg), sideways slide (2x10 rep. per leg), and backwards slide (2x10 rep. per leg). The participants may regress from level 2 to level 1.<br>Other: Sham LLLT<br>* - Same procedure as in the LLLT group with the exception of laser irradiation (0 mW mean output power).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain on movement | The participants are asked to rate their pain experienced on movement using an unidimensional visual analogue scale (VAS). No pain (0) is written in one end and worst imaginable pain (100) is written in the other end of the VAS tool. | 0, 3, 8, 26 and 52 weeks after randomization | 
| Pain at night | The participants are asked to rate their pain experienced in bed at night using an unidimensional visual analogue scale (VAS). No pain (0) is written in one end and worst imaginable pain (100) is written in the other end of the VAS tool. | 0, 3, 8, 26 and 52 weeks after randomization | 
| Pain at rest | The participants are asked to rate their pain experienced at rest in sitting position using an unidimensional visual analogue scale (VAS). No pain (0) is written in one end and worst imaginable pain (100) is written in the other end of the VAS tool. | 0, 3, 8, 26 and 52 weeks after randomization | 
| Pain in general | Pain in general is reported with the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire pain subscale. The subscale is based on Likert scales, each with five severity categories. The raw KOOS score is transformed to a 0-100 percentage score (higher is better). | 0, 3, 8, 26 and 52 weeks after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical function in daily living | Physical function in daily living is reported with the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire physical function in daily living subscale. The subscale is based on Likert scales, each with five severity categories. The raw KOOS score is transformed to a 0-100 percentage score (higher is better). | 0, 3, 8, 26 and 52 weeks after randomization | 
| Physical function in sports and recreational activities | Physical function in sports and recreational activities is reported with the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire physical function in sports and recreational activities subscale. The subscale is based on Likert scales, each with five severity categories. The raw KOOS score is transformed to a 0-100 percentage score (higher is better). | 0, 3, 8, 26 and 52 weeks after randomization | 
| Quality of life | Quality of life is reported with the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire quality of life subscale. The subscale is based on Likert scales, each with five severity categories. The raw KOOS score is transformed to a 0-100 percentage score (higher is better). | 0, 3, 8, 26 and 52 weeks after randomization | 
| Global health status assessment | The participants evaluate their change from baseline in terms of symptoms in general from 1 to 7 (1, no symptoms; 7, worse than ever). | 8 weeks after randomization | 
| Real time ultrasonography assessment of effusion | Maximum height will be measured. | 0, 3, 8, 26 and 52 weeks after randomization | 
| Real time ultrasonography assessment of neovascularization | Doppler area will be measured. | 0, 3, 8, 26 and 52 weeks after randomization | 
| Real time ultrasonography assessment of femur cartilage thickness |  | 0, 3, 8, 26 and 52 weeks after randomization | 
| 30 seconds chair stand | Last attempt counts if the participant is more than half way up. | 0, 3, 8, 26 and 52 weeks after randomization | 
| Knee extension active range of motion | A 30 cm goniometer is used. | 0, 3, 8, 26 and 52 weeks after randomization | 
| Knee flexion active range of motion | A 30 cm goniometer is used. | 0, 3, 8, 26 and 52 weeks after randomization | 
| Maximum pain free isometric quadriceps strength | A dynamometer is used: The dynamometer display is not visible during the procedure in order to blind the assessor for the level of pressure. | 0, 3, 8, 26 and 52 weeks after randomization | 
| Joint line pain pressure threshold | The most tender spot in the medial knee joint line is identified with palpation. Subsequently, a pain pressure threshold algometer is used at this spot. The display of the algometer is not visible during the procedure in order to blind the assessor for the level of pressure. | 0, 3, 8, 26 and 52 weeks after randomization | 
| Tibia bone pain pressure threshold | The most tender spot in the medial knee joint line is identified with palpation. Subsequently, a pain pressure threshold algometer is used 1.5 cm distally from this spot. The display of the algometer is not visible during the procedure in order to blind the assessor for the level of pressure. | 0, 3, 8, 26 and 52 weeks after randomization | 
| Analgesic drug consumption due to knee pain |  | 0, 3, 8, 26 and 52 weeks after randomization | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Knee osteoarthritis, Inflammation, Photobiomodulation, Low-level laser therapy, Double-blind, Randomized clinical trial, RCT