Participants’ recruitment and eligibility
Participants for this study will be consecutive patients with knee OA referred to the physiotherapy out-patient unit by the general practitioners in the four tertiary hospitals. Recruitment adverts using local posters with contact of the primary investigator will be pasted at various notice boards in the selected hospitals. To be eligible for the study, participants must meet the clinical criteria for the diagnosis of knee OA according to American College of Rheumatology (ACR) criteria for unilateral or bilateral symptomatic knee OA [45] in addition to being male or female of 30–65 years old. They will be excluded if they have any history of knee, hip or ankle surgery prior to the study, peripheral vascular disease, local or systemic infection, deformity in lower limbs, rheumatic disease other than OA, high-risk health status for exercise, unresolved balance or neurological disorder and received intra-articular joint injection within 4 weeks of beginning the study or history of a lower extremity exercise program for a minimum of six weeks prior to enrollment.
Baseline assessment
Physiotherapists at each of the physiotherapy out-patient unit of the selected hospitals will assess potential participants against the eligibility through clinical history, physical examination, and review of self-report questionnaires. After ensuring eligibility, participants will be given oral and written information regarding the procedures and potential risks of the study. Also, they will be given the option to take part and can withdraw from the study at any time should they choose to do so. Written informed consent will be then sought and obtained. Baseline socio-demographic and clinical variables such as age, gender, marital status, education level, occupational status, height, weight, body mass index, duration of knee pain and side affected will be collected using a prepared proforma. Baseline self-report clinical outcome assessments include; pain, physical function, quality of life and knee stability. Baseline objective outcome measure will be proprioception measurement. The flow of participants is depicted in Fig. 2.
Randomization and allocation concealment
After completing the baseline assessment, the participants will be randomized into three study groups in the ratio of 1:1:1. Simple randomization using a fishbowl technique will be carried out in each of the study centers by a third party, who will be completely blinded of the study content. The randomization will be achieved by the means of sealed envelopes, which will be prepared in advance and marked inside with letters A or B or C, representing group 1 (i.e. control or conventional physiotherapy), group 2 (i.e. two session per week of combined PR and KBA exercises) and group 3 (i.e. three session per week of combined PR and KBA exercises), respectively. A participant will be asked to pick an envelope from the bowl without replacement and when opened, the group written on the paper inside determines the intervention the participant will receive. Every new participant that met the inclusion criteria in each of the four research centers will be consecutively recruited and randomly assigned to any of the three groups in the same way until the required sample size is met.
Interventions
Participants in group 1 (control group) will receive a conventional physiotherapy program consisting of brief patient education, ultrasound therapy, stretching, strengthening and aerobic exercises. The program will be delivered twice weekly for 8 weeks except for the education program which will be provided in two sessions. The stretching exercises will be performed as warm-up and cool-down. Participants in group 2 will receive two sessions per week of combined PR and KBA for 8 weeks while participants in group 3 will receive three sessions per week of the same exercise program as for group 2. Both group 2 and 3 will receive the same conventional physiotherapy program as described for the group 1 prior to receiving the combined PR and KBA exercise program. All interventions will be delivered individually under the supervision of the treating physiotherapists. All participants will be encouraged to perform exercises consistent with their group allocation at least 2 times per day at home. A leaflet containing descriptions and pictures of their home exercises will be given to the participants to encourage adherence.
Brief patient education
Prior to exercise interventions, the participants will receive a brief education lasting approximately 15–20 minutes. The program will be delivered by the therapists responsible for exercise interventions. It will be provided in a group of 4–5 or more patients to save effort. The key topics to be addressed include: (1) understanding of knee OA, (2) lifestyle and physical activity/exercise, (3) diet and weight control, (4) self-management skills including active coping and pacing as well as correct use of medications (e.g. paracetamol), and (5) ergonomics and joint protection.
Ultrasound therapy (UST)
The affected knee of the participants will be treated with UST using the direct contact technique. A coupling medium (ultrasonic gel) will be used. The treatment parameters to be used include; frequency = 1MHZ, pulse duration = 2.0 W/cm2, pulse rest time = 1:1 (continuous mode), and duration = 7 minutes. The UST will precede the stretching and strengthening exercise program.
Stretching, strengthening and aerobic exercise
Participants will perform 3 lower-extremity stretching and strengthening exercises commonly prescribed for individuals with knee OA as described in previous studies [44, 46]. The stretching includes; hamstring stretch, quadriceps stretch and calf stretch for each limb. The stretching will be repeated as cool-down after completing the strengthening exercises.
Following the stretching, the participants will be instructed to perform the strengthening exercises including static quadriceps isometric, knee extension and leg curl exercise. Each exercise will be held for 15 seconds and repeat 6 times. Progression will be made by increasing the number of sets from 15 seconds hold to 30 seconds hold when the 15 seconds hold is no longer challenging, and the patient is performing activity with ease and good form. However, the exercise will be discontinued if the patient reports an exacerbation of symptoms. The details of the stretching and strengthening exercise protocol are presented in Table 1.
Table 1
Stretching and strengthening exercise program
Stretching exercise program |
Exercise | Description | Warm-up | Cool-down |
1.Hamstring stretch | Patient positioned in supine and keeps the knees and hips at 90–90 degrees position. The knee of one leg is then, extended progressively with the foot moving towards ceiling until it is perpendicular to the floor. Switch sides. | 15 s hold, 6 reps | 15 s hold, 6 reps |
2.Quadriceps stretch | Patient positioned in side-lying and grasps the forefoot behind. The forefoot or ankle is pulled to rear end. Switch sides. | 15 s hold, 6 reps | 15 s hold, 6 reps |
3.Calf stretch | Patient sits with the legs straight out in front. One leg is bend and a towel is placed around the ball of the opposite foot. While keeping the knee straight, pull the foot towards the body with the towel. Switch sides. | 15 s hold, 6 reps | 15 s hold, 6 reps |
Strengthening exercise program |
Exercise | Description | Intensity |
1.Static quadriceps isometrics | Patient stands with one leg straight and the knee of the opposite leg flexed, and the foot flat on the ground. A rolled towel or a cushion is placed underneath the straight leg’s knee. The straight knee is then pressed on the towel and the position is held. Switch sides. | 15 s hold, 6 reps |
2.Seated knee extension | Patient sits on a chair with one foot flat on the floor and straightens the opposite foot. Switch sides. | 15 s hold, 6 reps |
3. Lying leg curl | Patient lies prone and squeezes the inner thigh to keep the legs close next to each other. The legs are then bend as far as possible by bringing the heels in towards the buttocks. | 15 s hold, 6 reps |
The current guidelines consistently recommend low to moderate impact aerobic activity for individuals with OA [47, 48]. Considering this recommendation, participants will be advised to perform aerobic exercise (for example continuous outdoor walking or biking) at low to moderate intensity or tolerable speed for 20–30 minutes, 3–4 times per week at home.
Combined proprioceptive and kinesthesia, balance and agility exercise program
The exercise regimen of combined PR and KBA will be done by performing a series of proprioceptive, balance and walking agility exercises (Table 2). The PR and KBA exercise program was adapted from the program described by Mondam et al. [37] and Rogers et al. [44], respectively. Progression of exercise will be considered based on the participant’s ability. The exercise program will last for approximately 30–40 minutes per session. The details of the exercise program are presented in Table 2.
Table 2
Combined proprioceptive and kinesthesia, balance and agility exercise program
Exercise | Description | Timing |
1.One-leg balance on hard surface | Patient stand on one-leg with relaxed, upright posture. The opposite leg is bent at knee, hip and ankle. The position is held for 1 minute, followed by rest for 10–20 seconds and repeated twice. Rest for 1–2 minutes and switch sides. | 6 min |
2.Blind advanced one-leg balance on hard surface | Following the same guidelines for one-leg balance, keep eyes closed. Rest for 1–2 minutes and switch sides. | 6 min |
3.Toe walking on hard surface | Patient walk for a 20 meter distance with the toes pointing straight ahead and then walk with toes pointing out. Rest for 1–2 minutes and switch sides. | 2 min |
4.Cross body leg swings | Patient leans slightly forward with hands on a wall for support and weight on one leg. Swing the opposite leg in front of the body. Repeat 15 times. Rest for 1–2 minutes and switch sides. | 45 s |
5.Side stepping | Patient stands with feet together and move one leg laterally and then brought back to original position. Start with 15 steps and progress to 75 steps. Rest for 1–2 minutes and switch sides. | 60 s |
6.Semi-tandem walk | Patient walk heel-to-toe with heel landing just in front of and medial to great toe of opposite foot. Start with 15 steps and progress to 75 steps. Rest for 1–2 minutes and switch sides. | 1 min 30 s |
7.Cross-over walk | Patient walk forward by bringing each foot across midline of body. Start with 15 steps and progress to 75 steps. Rest for 1–2 minutes and switch sides. | 1 min 30 s |
8.Balance on foam (double-leg static) | Patient instructed to stand steady as long as possible (up to the 30 seconds limit). | 2 min |
9.Balance on foam (single-leg static) | Patient stands with single-leg support and the therapist attempts to perturb the patient’s balance in various directions for 10–30 seconds. Rest for 1–2 minutes and switch sides. | 2 min |
10.Balance on foam (dynamic) | Patient stands on foam and is instructed while performing small, rapid bouncing movements but without jumping. Patient instructed to flex and extend the knee to about 5–10 degrees maximum. | 2 min |
11.Multiple change in direction drill | Therapist provides hand signals directing the patient to move in different direction (i.e. forward-backward, right left lateral steps, diagonally backward- forward). | 1 min 30 s |
Proprioceptive exercise
The proprioceptive training will include a series of exercises to be performed with eyes opened and eyes closed on a hard surface (floor). Progression of each exercise will be achieved by increasing the duration and number of repetitions as the participant becomes more stable. However, the exercise will be discontinued if the patient reports an exacerbation of symptoms. The exercises are as follows; single-leg balance, blind advanced single-leg balance, toe walking and cross-body leg swings.
KBA exercise
The participants will perform first kinesthesia exercise before balance and then agility exercise. The kinesthetic training include side-stepping, semi tandem walking, and cross over walking. Participants will be instructed to begin with 15 steps and progress to a maximum of 75 steps per exercise. For the balance training, participants will be asked to stand on a foam surface and all exercises will be performed with both lower limbs. The exercise will be progressed based on the participant’s ability by starting with the less stressful and challenging ones and increasing the number of repetitions. Static balance exercises will be performed before progressing to dynamic balance exercises. Dynamic balance includes the addition of small, rapid bouncing movements. After learning dynamic balance activities, progression will be done by therapist perturbing the balance and stimulating neuromuscular mechanism. When a balance exercise continued to prove adequately challenging, the participant will not be asked to progress through different levels of instability. Each participant will perform static and dynamic balance with both limbs and single limb on a foam surface. The exercises will last for 2 minutes. Exercise will be discontinued if the patient reports an exacerbation of symptoms. Finally, the agility training involves multiple changes in direction which will be at a walking pace and progressed by adding more steps or increasing the pace [44]. All exercises will be progressed according to individual’s tolerance and abilities within the structure of the program. Number of steps or timing in terms of balance exercises will be reduced for participants who experienced difficulty or increase in pain, but no activity will be eliminated. Thus, the structure of the exercises will be maintained to make it safe and challenging for each participant.
Outcome assessments and follow-ups
The primary outcomes will be physical function to be measured by Ibadan Knee and Hip Osteoarthritis Outcome Measure (IKHOAM) and quality of life to be measured by Osteoarthritis Knee and Hip Quality of Life Questionnaire (OAKHQOL). The secondary outcomes will be pain intensity to be measured by Visual Analogue Scale (VAS) for pain, knee stability to be measured by Knee Outcome Survey-Activities of Daily Living Scale (KOS-ADLS) and proprioception to be measured using an electrogoniometer. Similar to previous trials on knee OA, if only one knee of the patient is affected, the evaluation of the outcomes will be done for this knee. If the patient has bilateral affectation of which only one meets the ACR criterion [45], only this knee will be evaluated. However, if the patient is having bilateral affectation according to the ACR criterion, the more painful knee will be randomly selected for outcome evaluation. Self-report outcomes not available in Hausa language (i.e. the native language of the majority of the target population) will be translated into Hausa using guidelines for the process of cross-cultural adaptation of self-report measures [49]. This is to ensure that reliable data is collected and participants who are unable to complete English measures are not excluded in the trial [50, 51].
All outcomes will be assessed pre-intervention, immediately post-intervention and at 3-month, 4-month and 6-month post-randomization (Fig. 2). Participants missing their regular appointments will be given makeup appointments until they reach the required sessions for each group. This will be done by contacting them through phone calls. All participants will be advised to refrain from other interventions during the trial except for those taking medications as prescribed by their physician.
Pain intensity
The Hausa VAS will be used to assess participants’ pain severity. It represents the intensity dimension by a 100 mm plain line with anchor points of “no pain” (0 mm), “moderated pain” (50 mm), and “worst imaginable pain” (100 mm) [52]. Participants will be asked to rate their current level of pain. The VAS is the most widely used scale for the assessment of pain in clinical settings and it has been reported to be reliable, valid and sensitive in patients with chronic musculoskeletal pain including knee OA [53–56].
Physical function
The physical function of the participants will be assessed with the Hausa version of the IKHOAM [57]. It contains 33 items with domains consisting of activity limitations, participation restrictions and physical performance tests to assess physical function. The measure is a Nigerian culture and environment-friendly clinical instrument developed for individuals with knee OA [58]. To obtain the patient’s percentage perceived level of physical function, the participant’s scores obtained are divided by the total possible score (232) and then multiplied by 100. Lower scores indicate a lower level of physical functioning [58]. The Hausa IKHOAM has been documented to be a reliable and valid measure of physical function in patients with knee OA [57].
Quality of life
The quality of life of the participants will be measure using the mini OAKHQOL [59]. The questionnaire consists of 20 items derived from the original 40-item questionnaire developed by Rat et al. [60]. The questionnaire consists of five dimensions subscales: physical activities, mental health, pain, social support, and social functioning; and three independent items addressing sexual life, professional life, and fear of being dependent. Each item is measured on a numerical rating scale from 0 to 10 and the mean item score becomes the corresponding dimension score [59]. The mini OAKHQOL has been shown to have good psychometric properties in terms of reliability, validity and factorial structure in subjects with knee and hip OA [59, 61].
Knee stability
Participants’ subjective reports of knee stability will be measured with the KOS-ADLS. It is a 14-item questionnaire that assesses symptom-related and specific functional limitations [62]. Six items assess knee symptoms (pain, stiffness, swelling, instability, weakness and limping) and eight items assess functional limitations (walking, stairs ascent/descent, standing, kneeling, squatting, sitting and rising from a sitting position) experienced in the last 1–2 days during the performance of daily activities. Each item is scored on a 6-point Likert scale (0–5 points) [63]. The score is transformed to a 0–100 point scale with the highest score indicating the absence of symptoms and functional limitations [62]. For the purpose of this study, only item pertaining to knee instability symptoms will be evaluated.
Proprioception
The participants' knee proprioceptive range of motion will be measured using an electrogoniometer (Ergotest Technology, Norway; range: 15–3200). The use of electrogoniometer for measuring the relative position of the knee joint has ben has been shown to be a reliable method for assessing joint proprioception [64]. To measure the proprioceptive range of motion, the participants will be asked to wear shorts for ease of attachment of the electrogoniometer to the knee joint [65]. The participants’ eyes will be blinded to eliminate visual feedback. They will be asked to sit on a high plinth with the hip at an angle of 80 degrees flexion in such a way that the distal hamstrings and knee joint are hanging freely at a resting position of 85 degrees knee flexion. A thin foam will be wrapped around the tested knee to minimize cutaneous sensation feedback from the attachment of the electrogoniometer [66]. While keeping the knee in neutral position, the electrogoniometer will be placed on the lateral side of the knee joint and its axis coinciding with the flexion/extension axis of the knee [67]. The goniometer will be kept in place using an elastic strap wrapped around the cushion padding. Participants will be instructed to bend the knee to a resting position of 85˚ of flexion and in this position they will be instructed to bend from resting position to the Target Angle (TA) of 70 degrees and hold there for 5 seconds, then return back to the resting position (85 degrees of flexion) [68, 69]. The participants will be then asked to repeat the procedure of bending the knee from the resting position of 85 degrees and say ‘YES’ on perceiving they reached the target position of 70˚ and hold. This angle is will be noted on the electrogoniometer and documented as the Perceived Angle (PA). The difference between TA and PA is the Absolute Angular Error (AAE) which will be documented [68]. This procedure will be repeated three times and the average of the three readings will be calculated and recorded as the error for each participant [64]. The inter-rater (between assessors) and intra-rater (within assessors) reliability of the electrogoniometer used in the present study will be evaluated.
Adverse events
All participants will be informed during recruitment the possibility of experiencing common adverse events related to exercise interventions such as muscle pull, soreness or cramp. They will be educated that these symptoms are temporary and self-limiting. Nonetheless, in case of any serious adverse events such as exacerbating joint pain, discernible joint swelling, excessive fatigue, light-headedness, angina and shortness of breath or dizziness, they will be advised to contact or report such events immediately to the primary investigator or treating therapist at the study center for prompt action.
Sample size estimation
Considering the minimal clinically important difference (MCID) of 12.8 points reported for the IKHOAM [70], the sample size was calculated a priori, to detect 12.8 points after intervention, and between-group (between group 1 and group 2 or group 3) difference of 3.0 points, assuming a standard deviation (SD) of 5.0 points, an effect size of 0.29; a statistical power of 80%; an alpha of 5% and a two-tailed t-test. The calculations suggested a sample size of 75 will be needed. However, while anticipating a 10% attrition rate (n = 8), a total sample size of 84 will be needed with 28 participants per group (three groups). The calculations were performed with the G-power 3.1.9.2 software (University of Dusseldorf, Dusseldorf, Germany) [71].