Effects of Exercise and Education in Patients With Chronic Pain After Total Knee Replacement

Study Overview
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Brief Summary
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The purpose of the study is to investigate whether a 12-week neuromuscular rehabilitation program (NEMEX-TJR) combined with pain neuroscience education (PNE) provides greater pain relief, improvement in physical function and quality of life than PNE alone in a population of patients with chronic pain after primary total knee arthroplasty. Hypothesis: Rehabilitation involving neuromuscular training and PNE will provide greater pain relief, improved function and improved quality of life compared to PNE alone at the primary endpoint, which is follow-up 12months after the start of the treatment.

Detailed Description
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Osteoarthritis is considered the most frequent cause of disability and pain in the elderly population, and the knee joint is one of the joints most commonly affected. End-stage osteoarthritis is often treated with knee replacement, and total knee arthroplasty is considered an effective treatment for pain relief and improved function. However, several studies have reported less favorable outcomes after total knee arthroplasty, and systematic reviews found chronic pain after total knee arthroplasty at 12 months post-operative in 13-17% of the patients and chronic pain rates at 2-7 years post-operative varying between 8-27%. No randomized controlled trials evaluating exercise and pain education treatments to patients with chronic pain after total knee arthroplasty exists, and this highlights the need for evidence-based knowledge of which treatment should be considered for this population.

Official Title
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Effect of Neuromuscular Exercise in Combination With Pain Neuroscience Education Compared to Pain Neuroscience Education Alone in Patients With Chronic Pain After Primary Total Knee Arthroplasty: A Randomized Controlled Trial

Conditions
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Arthroplasty, Replacement, Knee, Chronic Pain

Intervention / Treatment
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* Other: Neuromuscular exercises (NEMEX-TJR) and pain neuroscience education
* Other: Pain neuroscience education


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI) between 19-40 Subjects with primary total knee arthroplasty due to osteoarthritis ≥ 12 months post-operatively For the index knee, duration of knee pain > 6 months For the index knee, the average daily pain score ≥ 4 (moderate-to-severe pain) over the last week prior to visit on a numeric rating scale Exclusion Criteria: Specific reasons for chronic pain, such as loosening of implant, which requires revision surgery Secondary causes of arthritis to the knee, e.g. rheumatoid arthritis Surgery (including arthroscopy) of the index knee within 3 months prior to visit Injury to the index knee within 12 months prior to visit Recent history of acute pain affecting the lower limb and/or trunk Participation in other pain trials two weeks prior to this study Pregnancy Drug and alcohol abuse Previous neurologic illnesses or primary pain area other than knee, e.g. lower back, upper extremity pain or rheumatoid arthritis Lack of ability to adhere to protocol

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise and pain neuroscience education<br>Subjects with chronic pain after total knee replacement will receive 24 sessions of neuromuscular exercise therapy, supervised by a physiotherapist, and two sessions of pain neuroscience education, conducted by a physiotherapist | Other: Neuromuscular exercises (NEMEX-TJR) and pain neuroscience education<br>* 60min. of neuromuscular exercises (NEMEX-TJR) training two times a week for 3 months (12 weeks, 24 sessions). Physiotherapists will instruct and supervise the participants during the neuromuscular exercises. The aim of the neuromuscular exercise program is to restore normal movement, improve sensorimotor control, re-establishing normal motor program strategies and muscle activation. 60min. of pain neuroscience education at the beginning of intervention period and after 6 weeks. Both sessions will take 60min. and will be conducted by physiotherapists. The aim of the pain neuroscience education is to increase the pain neuroscience knowledge of the patients leading to a better understanding of their chronic pain and thereby engaging the patients in the treatment of their chronic pain and impaired function.<br>|
| Active Comparator: Pain neuroscience education<br>Subjects with chronic pain after total knee replacement will receive two sessions of pain neuroscience education, conducted by a physiotherapist | Other: Pain neuroscience education<br>* 60min. of pain neuroscience education at the beginning of intervention period and after 6 weeks. Both sessions will take 60min. and will be conducted by physiotherapists. The aim of the pain neuroscience education is to increase the pain neuroscience knowledge of the patients leading to a better understanding of their chronic pain and thereby engaging the patients in the treatment of their chronic pain and impaired function.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Knee Injury and Osteoarthritis Outcome Score4 (KOOS4) from baseline to 12months follow-up | The average score for four of the five KOOS subscales, covering pain, symptoms, difficulties in functions of daily living, and quality of life (KOOS4), with scores ranging from 0 (worst) to 100 (best). Between group comparisons of treatment effect (change in KOOS4 from baseline to 1 year follow-up) will be performed. | Baseline and at 3, 6 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in all five subscales of the KOOS | All five domains, covering pain, symptoms, difficulties in functions of daily living, sport and recreation and quality of life of the questionnaire will be used as secondary outcome with scores ranging from 0 (worst) to 100 (best). | Baseline and at 3, 6 and 12 months | 
| Rating of Global Perceived Effect | Global Perceived Effect will be assessed using the question: How are your knee problems now compared with before you entered this study? The question will be answered on a seven-point Likert scale ranging from 'Improved, an important improvement' to 'Worse, an important worsening'. | 3, 6 and 12 months | 
| Change in maximal pain intensity during rest (day and night), stair climbing, and walking on a Numeric Rating Scale (NRS) | Pain intensities on a NRS, where 0 represents no pain and 10 represents maximal pain in various situations. | Baseline and at 3, 6 and 12 months | 
| Change in use of Pain Medication | Dosage of pain medication used within last week | Baseline and at 3, 6 and 12 months | 
| Number of adverse events related to interventions | Serious and non-serious events that may occur during the intervention period will be identified in different ways: by self-reporting by the participants and by observation from the physiotherapists. Adverse events will be categorized as occurring in the index knee or other sites than the index knee. | 3 months | 
| Change in 40-meter fast-paced walk test | The amount of time in seconds it takes to complete the 40m | Baseline and at 3, 6 and 12 months | 
| Change in stair climb test | The amount of time in seconds it takes to complete ascending and descending of 9 stairs | Baseline and at 3, 6 and 12 months | 
| Change in 30-second chair stand test | Number of repetitions in 30-seconds | Baseline and at 3, 6 and 12 months | 
| Change in PainDETECT scores | The questionnaire is comprised of 3 major components: graduation of pain, pain course pattern and radiating pain. The maximum possible score is 38, and the minimum possible score is -1. | Baseline and at 3, 6 and 12 months | 
| Change in score from the Fear-avoidance Beliefs Questionnaire - Physical Activity | The scores range from 0 with completely disagree to 6 with completely agree and sums up to a total score between 0-24. | Baseline and at 3, 6 and 12 months | 
| Change in score from the Pain Catastrophizing Scale | Scores is rated on a 5-point scale with the 0 being not at all and 4 being all the time and the score can range from 0 to 52 points. | Baseline and at 3, 6 and 12 months | 
| Change in pinprick hyperalgesia at index knee and extrasegmental | The subject is to rate the pain intensity from the pinprick on a NRS, where 0 represents no pain and 10 represents maximal pain. | Baseline and at 3, 6 and 12 months | 
| Change in temporal summation at index knee and extrasegmental | The subject is to rate the pain intensity of the last test stimulus on a NRS, where 0 represents no pain and 10 represents maximal pain. | Baseline and at 3, 6 and 12 months | 
| Change in dynamic mechanical allodynia at the index knee and extrasegmental | The subject is to rate the pain intensity of a cotton swab on a NRS, where 0 represents no pain and 10 represents maximal pain. | Baseline and at 3, 6 and 12 months | 
| Change in deep somatic hyperalgesia at the index knee and extrasegmental | A bedside algometer will be applied on the skin over the vastus medialis muscle on the index side. The subject is to indicate immediately when the pressure becomes painful. | Baseline and at 3, 6 and 12 months | 
| Change in pressure pain thresholds at the index knee and extrasegmental | Pressure pain thresholds measured using a handheld algometer (Algometer Type II, Somedic AB, Hoerby, Sweden)) at the index knee and extrasegmental. | Baseline and at 3, 6 and 12 months | 
| Change in descending pain control | Conditioned pain modulation effect will be measured comparing the test stimuli without conditioning stimuli to the test stimuli with conditioning stimuli | Baseline and at 3, 6 and 12 months | 
| Change in number of sites with usual pain shaded on a body chart | Shaded markings on a body chart to indicate where usual pain is located | Baseline and at 3, 6 and 12 months | 
| Change in leg extension power | Leg extension power in a single-leg simultaneous hip and knee extension will be measured bilaterally. Highest measurement in watt is the outcome. | Baseline and at 3, 6 and 12 months | 
| Change in isometric muscle strength of knee extensors and flexors | Maximum isometric muscle strength (measured in Newtons) measured bilaterally in knee flexion and knee extension in a test using a handheld dynamometer (Lafayette manual muscle tester from Lafayette Instruments, USA). | Baseline and at 3, 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Pain, Total Knee Arthroplasty, Pain Neuroscience Education, Neuromuscular exercise (NEMEX-TJR)