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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Pain; Arthroplasty, Replacement, Knee
• Intervention / Treatment: Other: Neuromuscular exercises (NEMEX-TJR) and pain neuroscience education; Other: Pain neuroscience education

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jesper B Larsen, PhD-student; Phone Number: +4528268459; Email: jbl@hst.aau.dk

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Department of Occupational and Physiotherapy, Aalborg University Hospital
  • Farsø, Denmark, 9640
    • Department of Occupational- and Physiotherapy, Aalborg University Hospital
  • Thisted, Denmark, 7700
    • Department of Occupational- and Physiotherapy, Aalborg University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise and pain neuroscience education; 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; 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.
Active Comparator: Pain neuroscience education; Subjects with chronic pain after total knee replacement will receive two sessions of pain neuroscience education, conducted by a physiotherapist	Other: Pain neuroscience education; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital Anxiety and Depression Scale	The questionnaire consists of 14 items, which measures the patient level of anxiety and depression. The score in each item ranges from 0-3, giving scoring ranges from 0-21.	Baseline

Collaborators and Investigators

• Sponsor: Aalborg University
• Collaborators: Northern Orthopaedic Division, Denmark; The Danish Rheumatism Association; Svend Andersen Foundation; Lions Denmark
• Investigators: Study Chair: Pascal Madeleine, Dr.Scient, Aalborg University; Study Chair: Søren T Skou, PhD, University of Southern Denmark and Næstved-Slagelse-Ringsted Hospitals; Study Chair: Ole Simonsen, Dr.Med, Aalborg University Hospital; Study Chair: Lars Arendt-Nielsen, Dr.Med, Aalborg University; Principal Investigator: Jesper B Larsen, M.Sc., Aalborg University; Study Chair: Mogens B Laursen, PhD, Aalborg University Hospital

Publications and helpful links

General Publications

• Beswick AD, Wylde V, Gooberman-Hill R. Interventions for the prediction and management of chronic postsurgical pain after total knee replacement: systematic review of randomised controlled trials. BMJ Open. 2015 May 12;5(5):e007387. doi: 10.1136/bmjopen-2014-007387.
• Peat G, McCarney R, Croft P. Knee pain and osteoarthritis in older adults: a review of community burden and current use of primary health care. Ann Rheum Dis. 2001 Feb;60(2):91-7. doi: 10.1136/ard.60.2.91.
• Dieppe PA, Lohmander LS. Pathogenesis and management of pain in osteoarthritis. Lancet. 2005 Mar 12-18;365(9463):965-73. doi: 10.1016/S0140-6736(05)71086-2.
• Carr AJ, Robertsson O, Graves S, Price AJ, Arden NK, Judge A, Beard DJ. Knee replacement. Lancet. 2012 Apr 7;379(9823):1331-40. doi: 10.1016/S0140-6736(11)60752-6. Epub 2012 Mar 6.
• Beswick AD, Wylde V, Gooberman-Hill R, Blom A, Dieppe P. What proportion of patients report long-term pain after total hip or knee replacement for osteoarthritis? A systematic review of prospective studies in unselected patients. BMJ Open. 2012 Feb 22;2(1):e000435. doi: 10.1136/bmjopen-2011-000435. Print 2012.
• Davidson D, de Steiger R, Graves S, Tomkins A et al. Australian orthopaedic association national joint replacement registry. annual report. Adelaide:AOA;2010. . 2010
• Bhave A, Mont M, Tennis S, Nickey M, Starr R, Etienne G. Functional problems and treatment solutions after total hip and knee joint arthroplasty. J Bone Joint Surg Am. 2005;87 Suppl 2:9-21. doi: 10.2106/JBJS.E.00628. No abstract available.
• Wylde V, Dieppe P, Hewlett S, Learmonth ID. Total knee replacement: is it really an effective procedure for all? Knee. 2007 Dec;14(6):417-23. doi: 10.1016/j.knee.2007.06.001. Epub 2007 Jun 26.
• Wylde V, Dennis J, Beswick AD, Bruce J, Eccleston C, Howells N, Peters TJ, Gooberman-Hill R. Systematic review of management of chronic pain after surgery. Br J Surg. 2017 Sep;104(10):1293-1306. doi: 10.1002/bjs.10601. Epub 2017 Jul 6.
• Larsen JB, Skou ST, Arendt-Nielsen L, Simonsen O, Madeleine P. Neuromuscular exercise and pain neuroscience education compared with pain neuroscience education alone in patients with chronic pain after primary total knee arthroplasty: study protocol for the NEPNEP randomized controlled trial. Trials. 2020 Feb 24;21(1):218. doi: 10.1186/s13063-020-4126-5.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 20, 2019
• First Submitted That Met QC Criteria: March 21, 2019
• First Posted (Actual): March 22, 2019

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Chronic Pain; Total Knee Arthroplasty; Pain Neuroscience Education; Neuromuscular exercise (NEMEX-TJR)
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain
• Other Study ID Numbers: N-20180046

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual subject data that underlie the results reported in the publication will be shared after deidentification (text, tables, figures, appendices)
• IPD Sharing Time Frame: Beginning 3 months following publication. No end date.
• IPD Sharing Access Criteria: Researchers that provide a methodologically sound plan
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No