Back to resultsExercise Therapy in Combination With Central Nervous System-targeted Treatment for Osteoarthritis
Primary Purpose
Osteoarthritis, Osteo Arthritis Knee
Status
Unknown status
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
NEMEX program combined with a CNS-focused protocol
NEMEX program
Sponsored by
About this trial
This is an interventional treatment trial for Osteoarthritis
Eligibility Criteria
Inclusion Criteria:
- Patients with symptomatic and radiographically-confirmed tibiofemoral KOA (e.g. Kellgren-Lawrence ≥2, scored by an orthopaedic surgeon, not scheduled for total knee replacement [decision among other factors based on pain, function and radiographic severity.
- Diagnosis of KOA according to the EULAR classification criteria: adults aged >40 years with usage-related knee pain, only short-lived (<30min) morning stiffness, functional limitation (based on yes/no to the following question: Is your functional level reduced as compared to before your knee symptoms first started?) and one or more typical examination findings (crepitus, restricted movement, bony enlargement). The presence of this cluster correctly diagnosed 99% of cases with KOA.
Exclusion Criteria:
- Less than mild functional limitations (a score above 75 on a 0-100 worst to best scale in the Spanish version of the self-report questionnaire Knee injury and Osteoarthritis Outcome Score (KOOS)4 defined as the average score for the subscale scores for pain, symptoms, activities of daily living (ADL) and quality of life (QOL).
- Previous knee replacement or any other lower limb surgery in the affected knee within the previous 3 months.
- Fracture of the affected extremity within the previous 6 months.
- Initiation of opioid analgesia or any form of injection (i.e. corticosteroid, hyaluronic acid, platelet-rich plasma) for knee pain within the previous 30 days.
- Physical impairments unrelated to the knee that would prevent safe participation in exercise.
- Any comorbidity that prevents from participating in the interventions (e.g.uncontrolled hypertension, moderate to high risk for cardiac complications)
- Any skin or medical condition preventing tactile stimulation on the knee.
- Inability to comprehend and complete study assessments or comply with study instructions (e.g. illiteracy, cognitive or visual impairments).
- Inability to a priori attend or complete the proposed course of intervention and follow-up schedule.
Sites / Locations
- University of ValenciaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Exercise Therapy With CNS Treatment
Exercise Therapy alone
Arm Description
NEMEX program combined with a CNS-focused protocol
NEMEX program alone
Outcomes
Primary Outcome Measures
The Knee injury and Osteoarthritis Outcome Score subscales (KOOS4)
The primary outcome is the between-group difference in change in the mean score on four Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, covering pain, symptoms, activities of daily living, and quality of life (KOOS4).
The four patient-relevant subscales of KOOS are scored separately: Pain (9 items); Symptoms (7 items); ADL Function (17 items); Quality of Life (4 items). A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the four scores is calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as common in orthopaedic assessment scales and generic measures. Scores between 0 and 100 represent the percentage of total possible score achieved.
Secondary Outcome Measures
The Knee injury and Osteoarthritis Outcome Score (KOOS)
The KOOS is a knee-specific instrument, developed to assess the patients' opinion about their knee and associated problems. It holds 42 items in 5 separately scored subscales; Pain, other Symptoms, Function in daily living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related Quality of Life (QOL).
The scores on all five patient-relevant subscales of KOOS are scored separately: Pain (9 items); Symptoms (7 items); ADL Function (17 items); Sport and Recreation Function (5 items); Quality of Life (4 items). A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as common in orthopaedic assessment scales and generic measures. Scores between 0 and 100 represent the percentage of total possible score achieved.
Pain intensity: NRS
Participants will be presented with four numerical rating scales anchored with 0 ("no pain") and 10 ("pain as bad as you can imagine"): 1) rating the most intense pain over the last week, 2) rating the least intense pain over the last week, 3) rating the average pain intensity over the last week, and 4) rating the pain right now. The scores will be averaged to calculate a final pain intensity score out of 10
Sensitivity to physical activity
Participants will be asked to rate their level of knee discomfort before, during, and after the 30-s chair-stand test in accordance with previous studies (Wideman et al., 2014). Knee discomfort will be ranked three times on a verbal rating scale that ranged from 0 (no discomfort) to 100 (extreme discomfort), once immediately before the task, once during the middle and once at the end of the task. An index of sensitivity to physical activity (SPA) will be calculated by subtracting participants' first rating from their last rating.
General health
General health will be assessed using the Spanish version of the EuroQol Group 5-Dimension (EQ-5D-5L) self-reported questionnaire. EQ-5D-5L is a questionnaire with 5 dimensions (mobility, self-care, usual activities, pain/ discomfort, and anxiety/depression) and 5 levels in each dimension (no problems, slight, moderate, severe, and un- able or extreme). Each health state is usually represented using a 5-digit number (profile) where 11111 indicates perfect health and 55555 the worst health state or pits state.
Cortical representation
The two-point discrimination (TPD) threshold is considered a clinical signature of cortical representation primary somatosensory representation. The TPD threshold will be measured using a mechanical sliding calliper (Duratech TA-2081, precision = 1 mm) in the vertical direction on the affected knee using suprathreshold (but non-noxious stimuli) and following an established protocol.
Pressure pain thresholds
A standardized protocol for evaluating PPTs will be used. Two test sites in the peripatellar region (3 cm medial and lateral to the midpoint of the medial and lateral edge of patella, respectively) and one distant site on the ipsilateral trapezius muscle (midpoint between spinous process of C7 and lateral border of acromion) will be selected for measurement. The PPT will be measured using an analogue Fisher algometer (Force Dial model FDK 40) with a surface area of 1cm2. The algometer probe tip was applied perpendicular to the skin at a rate of 1kg/cm2/s until the first onset of pain. Three measures were performed on each site with a 30 s interstimulus interval between each measurement and the mean was taken for analysis.
Central Sensitization Inventory
To identify key symptoms associated with augmented central pain processing mechanisms (e.g.central sensitization), the Spanish version of the Central Sensitization Inventory will be used (Cuesta-Vargas et al., 2016). The CSI provides reliable and valid data that quantify the severity of several symptoms of CS (Scerbo et al., 2017).
Conditioned Pain Modulation
Conditioned pain modulation (CPM) was tested using the upper extremity submaximal effort tourniquet test. Three trials of PPT measures at the two sites in the peripatellar region (medial and lateral to the midpoint of the medial and lateral edge of patella) were taken immediately following deflation.
Number of participants with adverse events and number of adverse events
Adverse events (AE) and serious adverse events (SAEs) will be recorded at all follow-ups by asking patients about potential AEs using open-probe questioning to ensure that all AEs are recorded. In addition, the physiotherapist will record any adverse events that the patient experiences or talks about during treatment.
Global perceived effect, patient acceptable symptom state and treatment failure
Global perceived effect will be assessed with the question: "How are your knee problems now compared with before you entered this study?" This question will be answered on a Likert scale ranging from 1 ("very much improved") to 7 ("very much worse").
Satisfaction with current knee function will be evaluated by the following question: "When you think of your knee function, will you consider your current condition as satisfying?"
Compliance, exercise level/intensity and other treatments received during the study
Compliance with treatment sessions will be monitored by the supervising physiotherapists using an individual treatment diary where the number of sessions, progression of the exercises (e.g. level of difficulty at which all specific exercises are performed each session), time of day and duration of each clinic session will be recorded.
Knee flexor and extensor strength
Isometric knee flexor and extensor strength testing with modified hand-held dynamometry will be performed.
Number of chair stands in 30 seconds
As performance-based tests of physical function, the number of chair stands will be assessed. These tests have been recommended as performance-based tests of physical function representing typical activities relevant to individuals diagnosed with KOA.
40 m fast-paced walk test
As performance-based tests of physical function, the 40 m fast-paced walk test will be assessed in seconds. These tests have been recommended as performance-based tests of physical function representing typical activities relevant to individuals diagnosed with KOA.
Full Information
NCT ID
NCT03681613
First Posted
September 18, 2018
Last Updated
March 28, 2020
Sponsor
University of Valencia
1. Study Identification
Unique Protocol Identification Number
NCT03681613
Brief Title
Exercise Therapy in Combination With Central Nervous System-targeted Treatment for Osteoarthritis
Official Title
Randomized Controlled Trial of Exercise Therapy in Combination With Central Nervous System-targeted Treatment Compared With Exercise Therapy Alone for Treatment of People With Knee Osteoarthritis
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 7, 2019 (Actual)
Primary Completion Date
October 2020 (Anticipated)
Study Completion Date
December 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Valencia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The aim of this study is to investigate if exercise therapy comprising the NEMEX program in combination with a CNS-targeted treatment using GMI and SDT is superior to exercise therapy alone in improving self-reported pain, function, quality of life and objective measures related to hyperexcitability of the CNS (e.g. central sensitization) in people with KOA.
Detailed Description
Participants will be randomized to one of two treatments initiated after randomization: the NEMEX program combined with a CNS-focused protocol or the NEMEX program alone.
The NEMEX program will consist of 12-weeks of individualized and supervised exercise sessions applied twice weekly (n=24 sessions). Each exercise session will last approximately 60minutes and include three parts: warming up, a circuit program and cooling down.
The CNS-targeted treatment will consist of 12-week individualized and supervised sessions applied twice weekly. Each training session will last approximately 30 minutes and include three parts, which are further explained below: 1) discussion of the participant's knee pain experience from a pain neuroscience perspective, 2) graded SDT and 3) GMI training.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis, Osteo Arthritis Knee
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
104 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Exercise Therapy With CNS Treatment
Arm Type
Experimental
Arm Description
NEMEX program combined with a CNS-focused protocol
Arm Title
Exercise Therapy alone
Arm Type
Experimental
Arm Description
NEMEX program alone
Intervention Type
Other
Intervention Name(s)
NEMEX program combined with a CNS-focused protocol
Other Intervention Name(s)
Graded Motor Imagery, Sensory Discrimination Training, NEMEX program
Intervention Description
The NEMEX program will consist of 12-weeks of individualized and supervised exercise sessions applied twice weekly (n=24 sessions). Each exercise session will last approximately 60minutes and include three parts: warming up, a circuit program and cooling down.
The CNS-targeted treatment will consist of 12-week individualized and supervised sessions applied once weekly. Each training session will last approximately 30 minutes and include three parts, which are further explained below: 1) discussion of the participant's knee pain experience from a pain neuroscience perspective, 2) graded SDT and 3) GMI training.
Intervention Type
Other
Intervention Name(s)
NEMEX program
Intervention Description
The NEMEX program will consist of 12-weeks of individualized and supervised exercise sessions applied twice weekly (n=24 sessions). Each exercise session will last approximately 60minutes and include three parts: warming up, a circuit program and cooling down.
Primary Outcome Measure Information:
Title
The Knee injury and Osteoarthritis Outcome Score subscales (KOOS4)
Description
The primary outcome is the between-group difference in change in the mean score on four Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, covering pain, symptoms, activities of daily living, and quality of life (KOOS4).
The four patient-relevant subscales of KOOS are scored separately: Pain (9 items); Symptoms (7 items); ADL Function (17 items); Quality of Life (4 items). A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the four scores is calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as common in orthopaedic assessment scales and generic measures. Scores between 0 and 100 represent the percentage of total possible score achieved.
Time Frame
baseline, post-intervention (after 12 weeks) and 6 and 12 months after initiating the treatment
Secondary Outcome Measure Information:
Title
The Knee injury and Osteoarthritis Outcome Score (KOOS)
Description
The KOOS is a knee-specific instrument, developed to assess the patients' opinion about their knee and associated problems. It holds 42 items in 5 separately scored subscales; Pain, other Symptoms, Function in daily living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related Quality of Life (QOL).
The scores on all five patient-relevant subscales of KOOS are scored separately: Pain (9 items); Symptoms (7 items); ADL Function (17 items); Sport and Recreation Function (5 items); Quality of Life (4 items). A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as common in orthopaedic assessment scales and generic measures. Scores between 0 and 100 represent the percentage of total possible score achieved.
Time Frame
baseline, post-intervention (after 12 weeks) and 6 and 12 months after initiating the treatment
Title
Pain intensity: NRS
Description
Participants will be presented with four numerical rating scales anchored with 0 ("no pain") and 10 ("pain as bad as you can imagine"): 1) rating the most intense pain over the last week, 2) rating the least intense pain over the last week, 3) rating the average pain intensity over the last week, and 4) rating the pain right now. The scores will be averaged to calculate a final pain intensity score out of 10
Time Frame
baseline, post-intervention (after 12 weeks) and 6 and 12 months after initiating the treatment
Title
Sensitivity to physical activity
Description
Participants will be asked to rate their level of knee discomfort before, during, and after the 30-s chair-stand test in accordance with previous studies (Wideman et al., 2014). Knee discomfort will be ranked three times on a verbal rating scale that ranged from 0 (no discomfort) to 100 (extreme discomfort), once immediately before the task, once during the middle and once at the end of the task. An index of sensitivity to physical activity (SPA) will be calculated by subtracting participants' first rating from their last rating.
Time Frame
baseline, post-intervention (after 12 weeks) and 6 and 12 months after initiating the treatment
Title
General health
Description
General health will be assessed using the Spanish version of the EuroQol Group 5-Dimension (EQ-5D-5L) self-reported questionnaire. EQ-5D-5L is a questionnaire with 5 dimensions (mobility, self-care, usual activities, pain/ discomfort, and anxiety/depression) and 5 levels in each dimension (no problems, slight, moderate, severe, and un- able or extreme). Each health state is usually represented using a 5-digit number (profile) where 11111 indicates perfect health and 55555 the worst health state or pits state.
Time Frame
baseline, post-intervention (after 12 weeks) and 6 and 12 months after initiating the treatment
Title
Cortical representation
Description
The two-point discrimination (TPD) threshold is considered a clinical signature of cortical representation primary somatosensory representation. The TPD threshold will be measured using a mechanical sliding calliper (Duratech TA-2081, precision = 1 mm) in the vertical direction on the affected knee using suprathreshold (but non-noxious stimuli) and following an established protocol.
Time Frame
baseline, post-intervention (after 12 weeks) and 6 and 12 months after initiating the treatment
Title
Pressure pain thresholds
Description
A standardized protocol for evaluating PPTs will be used. Two test sites in the peripatellar region (3 cm medial and lateral to the midpoint of the medial and lateral edge of patella, respectively) and one distant site on the ipsilateral trapezius muscle (midpoint between spinous process of C7 and lateral border of acromion) will be selected for measurement. The PPT will be measured using an analogue Fisher algometer (Force Dial model FDK 40) with a surface area of 1cm2. The algometer probe tip was applied perpendicular to the skin at a rate of 1kg/cm2/s until the first onset of pain. Three measures were performed on each site with a 30 s interstimulus interval between each measurement and the mean was taken for analysis.
Time Frame
baseline, post-intervention (after 12 weeks) and 6 and 12 months after initiating the treatment
Title
Central Sensitization Inventory
Description
To identify key symptoms associated with augmented central pain processing mechanisms (e.g.central sensitization), the Spanish version of the Central Sensitization Inventory will be used (Cuesta-Vargas et al., 2016). The CSI provides reliable and valid data that quantify the severity of several symptoms of CS (Scerbo et al., 2017).
Time Frame
baseline, post-intervention (after 12 weeks) and 6 and 12 months after initiating the treatment
Title
Conditioned Pain Modulation
Description
Conditioned pain modulation (CPM) was tested using the upper extremity submaximal effort tourniquet test. Three trials of PPT measures at the two sites in the peripatellar region (medial and lateral to the midpoint of the medial and lateral edge of patella) were taken immediately following deflation.
Time Frame
baseline, post-intervention (after 12 weeks) and 6 and 12 months after initiating the treatment
Title
Number of participants with adverse events and number of adverse events
Description
Adverse events (AE) and serious adverse events (SAEs) will be recorded at all follow-ups by asking patients about potential AEs using open-probe questioning to ensure that all AEs are recorded. In addition, the physiotherapist will record any adverse events that the patient experiences or talks about during treatment.
Time Frame
During follow-up
Title
Global perceived effect, patient acceptable symptom state and treatment failure
Description
Global perceived effect will be assessed with the question: "How are your knee problems now compared with before you entered this study?" This question will be answered on a Likert scale ranging from 1 ("very much improved") to 7 ("very much worse").
Satisfaction with current knee function will be evaluated by the following question: "When you think of your knee function, will you consider your current condition as satisfying?"
Time Frame
12 months after initiating the treatment
Title
Compliance, exercise level/intensity and other treatments received during the study
Description
Compliance with treatment sessions will be monitored by the supervising physiotherapists using an individual treatment diary where the number of sessions, progression of the exercises (e.g. level of difficulty at which all specific exercises are performed each session), time of day and duration of each clinic session will be recorded.
Time Frame
Up to 12 weeks
Title
Knee flexor and extensor strength
Description
Isometric knee flexor and extensor strength testing with modified hand-held dynamometry will be performed.
Time Frame
Baseline, post-intervention (after 12 weeks) and 6 and 12 months after initiating the treatment
Title
Number of chair stands in 30 seconds
Description
As performance-based tests of physical function, the number of chair stands will be assessed. These tests have been recommended as performance-based tests of physical function representing typical activities relevant to individuals diagnosed with KOA.
Time Frame
Baseline, post-intervention (after 12 weeks) and 6 and 12 months after initiating the treatment
Title
40 m fast-paced walk test
Description
As performance-based tests of physical function, the 40 m fast-paced walk test will be assessed in seconds. These tests have been recommended as performance-based tests of physical function representing typical activities relevant to individuals diagnosed with KOA.
Time Frame
Baseline, post-intervention (after 12 weeks) and 6 and 12 months after initiating the treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
41 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with symptomatic and radiographically-confirmed tibiofemoral KOA (e.g. Kellgren-Lawrence ≥2, scored by an orthopaedic surgeon, not scheduled for total knee replacement [decision among other factors based on pain, function and radiographic severity.
Diagnosis of KOA according to the EULAR classification criteria: adults aged >40 years with usage-related knee pain, only short-lived (<30min) morning stiffness, functional limitation (based on yes/no to the following question: Is your functional level reduced as compared to before your knee symptoms first started?) and one or more typical examination findings (crepitus, restricted movement, bony enlargement). The presence of this cluster correctly diagnosed 99% of cases with KOA.
Exclusion Criteria:
Less than mild functional limitations (a score above 75 on a 0-100 worst to best scale in the Spanish version of the self-report questionnaire Knee injury and Osteoarthritis Outcome Score (KOOS)4 defined as the average score for the subscale scores for pain, symptoms, activities of daily living (ADL) and quality of life (QOL).
Previous knee replacement or any other lower limb surgery in the affected knee within the previous 3 months.
Fracture of the affected extremity within the previous 6 months.
Initiation of opioid analgesia or any form of injection (i.e. corticosteroid, hyaluronic acid, platelet-rich plasma) for knee pain within the previous 30 days.
Physical impairments unrelated to the knee that would prevent safe participation in exercise.
Any comorbidity that prevents from participating in the interventions (e.g.uncontrolled hypertension, moderate to high risk for cardiac complications)
Any skin or medical condition preventing tactile stimulation on the knee.
Inability to comprehend and complete study assessments or comply with study instructions (e.g. illiteracy, cognitive or visual impairments).
Inability to a priori attend or complete the proposed course of intervention and follow-up schedule.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Javier Peral Pérez, PhD Student
Phone
+34650510292
Email
jperalperez@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Enrique Lluch Girbés, PhD
Organizational Affiliation
University of Valencia
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Søren Thorgaard Skou, PhD
Organizational Affiliation
University of Southern Denmark
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Javier Peral Pérez, PhD student
Organizational Affiliation
University of Alcalá
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Enrique Lluch, PhD
Phone
+34 96 398 38 53
Email
Enrique.Lluch@uv.es
12. IPD Sharing Statement
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Exercise Therapy in Combination With Central Nervous System-targeted Treatment for Osteoarthritis
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