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Exercise Therapy for Osteoarthritis Pain: How Does it Work? (KOA-PAIN)

Primary Purpose

Knee Osteoarthritis

Status

Recruiting

Phase

Not Applicable

Locations

Belgium

Study Type

Interventional

Intervention

Muscle Strengthening Training

Behavioral graded activity

About this trial

This is an interventional basic science trial for Knee Osteoarthritis focused on measuring Osteoarthritis, Exercise, Acute effects, Inflammation, Endogenous hypoalgesia

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

KOA according to the clinical American College of Rheumatology (ACR) criteria. The clinical ACR criteria for KOA are: knee pain and at least 3 of the 6 following features: age ≥50, morning stiffness <30 minutes, crepitus, bony tenderness, bony enlargement, no palpable warmth. KOA will be confirmed with radiographs, including anterior-posterior (AP) and medio-lateral (ML) radiographs for imaging the tibiofemoral joint, and an axial view for imaging the patellofemoral joint. Kellgren and Lawrence (K&L) grading system for OA will be applied, with K&L grade 2 or higher defined as OA; radiographic KOA is defined as definite osteophytes and possible joint space narrowing.
pain, nominated by the patient as 3 /10 or higher on a visual analogue scale on most days of the last 3 months
aged ≥ 50 years.

Exclusion Criteria:

treatment with exercise therapy or joint infiltrations (e.g., corticosteroids, hyaluronic acid) in the preceding 6 months;
being on a waiting list for knee replacement;
any contra-indication for exercise therapy as established by the treating physician;
corticosteroid infiltrations in the last 6 months;
cognitive impairment (unable to understand the test instructions and/or Mini Mental State Examination score <23/30);
unable to understand the Dutch language;
inflammation unrelated to OA (e.g. due to acute or chronic infection) established by CRP>10mg/L.
presence of a disorder and/or medication that influences pain and/or the immune system

Sites / Locations

Vrije Universiteit Brussel (VUB)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

No Intervention

Arm Label

Muscle Strengthening Training (MST)-group

Behavioral Graded Activity (BGA)-group

Control group

Arm Description

Subjects allocated to the MST group (n=30) will perform a muscle strengthening training program of 12 weeks.

Subjects allocated to the BGA group (n=30) will perform a rehabilitation program according to the principles of behavioural graded activity for a period of 12 weeks.

Subjects allocated to the control group (n=30) have to maintain their current life-style and treatment (if any) and to refrain from other new interventions during 24 weeks.

Outcomes

Primary Outcome Measures

Knee pain as primary study outcome

Pain is the primary outcome as it is the primary and most disabling symptom in OA. The pain subscale of the WOMAC Osteoarthritis Index LK3.0 questionnaire will be used for the assessment of pain severity. The Knee injury and Osteoarthritis Outcome Score (KOOS) includes WOMAC Osteoarthritis Index LK3.0 in its complete and original format (with permission). WOMAC (and therefore the pain and symptoms subscale of the KOOS) is a valid tool for subjects with KOA. The KOOS is proven to generate valid and reliable scores.

Knee pain as primary study outcome

Secondary Outcome Measures

Different subtypes of pain: pain

Pain will be measured using the Visual analogue scale (VAS).

Different subtypes of pain: intermittent pain

Intermittent pain will be measured using a short and easily applicable self-reported measure, i.e. intermittent and constant pain (ICOAP).

Different subtypes of pain: constant pain

Constant pain, will be measured using a short and easily applicable self-reported measure, i.e. Intermittent and constant pain (ICOAP).

Different subtypes of pain: central sensitization

Central sensitization will be measured using an easily applicable self-reported measure i.e. Central Sensitization Inventory (CSI).

Function in daily living (KOOS subscale)

Function in daily living will be measured using self-reported measures. The KOOS function in daily living (ADL) subscale and functioning in sports and recreation subscale are reliable and valid scales to measure function in people with osteoarthritis. The patient global assessment (PGA) is a recommended questionnaire in clinical trials of rehabilitation interventions for OA and it measures the improvement or deterioration of their condition.

Function in daily living (PGA)

Function in daily living will be measured using self-reported measures. The patient global assessment (PGA) is a recommended questionnaire in clinical trials of rehabilitation interventions for OA and it measures the improvement or deterioration of their condition.

Treatment adherence

Patient adherence for the treatment sessions will be calculated as the ratio of the number of treatment sessions that were actually carried out versus the number of prescribed sessions. Compliance will be calculated as the ratio of the total training duration (recorded in the logbooks) versus the prescribed total training duration, multiplied by 100.

Treatment compliance

Compliance will be calculated as the ratio of the total training duration (recorded in the logbooks) versus the prescribed total training duration, multiplied by 100.

Health care cost effectiveness

Medical consumption, the type, dose, method of administration and frequency of analgesic, NSAID or symptom-modifying medication, as well as surgeries (total or partial knee replacements) will be recorded. Health care use will be evaluated using the combination of three questionnaires: (1) the Medical Consumption Questionnaire (2) the Productivity Cost Questionnaire and (3) the EuroQol EQ-5D.

Full Information

NCT ID

NCT04362618

First Posted

February 28, 2020

Last Updated

May 26, 2023

Sponsor

Vrije Universiteit Brussel

Collaborators

Universitair Ziekenhuis Brussel, AZ St.-Dimpna Geel

1. Study Identification

Unique Protocol Identification Number

NCT04362618

Brief Title

Exercise Therapy for Osteoarthritis Pain: How Does it Work?

Acronym

KOA-PAIN

Official Title

Exercise Therapy for Osteoarthritis Pain: How Does it Work?

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 5, 2020 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Vrije Universiteit Brussel

Collaborators

Universitair Ziekenhuis Brussel, AZ St.-Dimpna Geel

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

International guidelines recommend exercise as the first choice treatment for knee osteoarthritis (KOA). Muscle strengthening training (MST) and behavioural graded activity (BGA) show comparable effects on KOA pain, but the mechanisms of action are unclear. Understanding these mechanisms is necessary to tailor exercise therapy towards specific mediators and thereby optimize treatment effects. Based on previous studies, both exercise-induced anti-inflammation and endogenous analgesia are promising pathways for pain reduction after exercise therapy. This study aims to examine (anti)-inflammation and endogenous analgesia as mediators for the effect of MST and/or BGA on pain in patients with KOA. Therefore, a 3-arm randomized clinical trial is established: 12 weeks of muscle strengthening training, behavioural graded activity or control. Mediator analysis will be performed. Unravelling the mechanisms of action of exercise therapy in KOA will not only be extremely valuable for researchers, but also for exercise immunology and pain scientists. The results of this research will also find their way into clinical practice: thanks to the current project, tailoring exercise therapy programs towards specific mechanistic factors and thereby optimizing treatment effects will be at the horizon for patients suffering from KOA.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Knee Osteoarthritis

Keywords

Osteoarthritis, Exercise, Acute effects, Inflammation, Endogenous hypoalgesia

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

The patients will be randomly allocated to 12 weeks of either muscle strengthening training (MST), behavioural graded activity (BGA) or control. Randomization will be performed by using the method of randomly permuted blocks, utilising a computer-generated random number sequence. To keep both intervention groups balanced, randomization will be stratified for sex (male versus female) baseline inflammation status (hsCRP<3mg/L versus hsCRP ≥3mg/L) and baseline central sensitization status (central sensitization inventory (CSI) score <40 versus CSI score ≥ 40). A list with patient numbers and the group allocation that results from this randomization procedure will be securely stored and only an independent researcher will have direct access to the randomization list. Patients will be scheduled to receive their first assessment within 1 week of randomisation. Patients will be recruited in primary care and participating hospitals. Announcements will be placed in newspapers, pharmacies etc.

Masking

Care ProviderInvestigatorOutcomes Assessor

Masking Description

Outcome assessors will be blinded to the maximal extent possible. With regard to this, patients will be asked not to communicate with the assessors about the intervention received. The researcher who is responsible for the acute measurements, is not blinded for group allocation but the researcher responsible for the basal measurements is. Both researchers are blinded for the outcome analyses. Furthermore, at the end of each assessment, the success of assessor blinding will be examined by asking whether the assessor thought the participant had received the experimental or control intervention, including the percentage of certainty. The physiotherapists providing BGA will not be involved in providing MST, and vice versa. Additionally, the physiotherapists will be blinded for outcome measures. The statistician will be blinded to the allocation of the treatment groups and statistical analyses will be performed in a blinded manner.

Allocation

Randomized

Enrollment

90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Muscle Strengthening Training (MST)-group

Arm Type

Experimental

Arm Description

Subjects allocated to the MST group (n=30) will perform a muscle strengthening training program of 12 weeks.

Arm Title

Behavioral Graded Activity (BGA)-group

Arm Type

Experimental

Arm Description

Subjects allocated to the BGA group (n=30) will perform a rehabilitation program according to the principles of behavioural graded activity for a period of 12 weeks.

Arm Title

Control group

Arm Type

No Intervention

Arm Description

Subjects allocated to the control group (n=30) have to maintain their current life-style and treatment (if any) and to refrain from other new interventions during 24 weeks.

Intervention Type

Other

Intervention Name(s)

Muscle Strengthening Training

Intervention Description

Muscle strengthening training will take place for a period of 12 weeks, in which participants will have 36 exercise sessions (18 at the hospital under supervision of a physiotherapist; 18 unsupervised at home) planned. Muscles of the leg (i.e. quadriceps, hip ab- and adductors) will be trained at 3 set of 10 repetitions at 80% of 1RM with the use of elastic bands. 1RM will be assessed at baseline and the exercise intensity will be progressively increased by 10% of 1RM every two sessions from 50 up to 70-80 % of 1RM. Every 6 sessions, the 1RM will be reassessed and the training resistances will be adapted.

Intervention Type

Behavioral

Intervention Name(s)

Behavioral graded activity

Intervention Description

Subjects will receive a behavioural treatment integrated within the concepts of operant conditioning with exercise therapy for a period of 12 weeks, in which the subjects will have maximum 36 BGA sessions (min. 13- max. 18 at the hospital under supervision of a physiotherapist; 18 unsupervised at home) planned. The purpose of BGA is to increase the level of activities in a time-contingent manner and increase the level of physical activity in the subject's daily lives. BGA consists of 3 phases: pain education (phase 1), treatment phase in which subjects increase their level of activity gradually (phase 2) and integration of learned principles in daily live (phase 3).

Primary Outcome Measure Information:

Title

Knee pain as primary study outcome

Description

Time Frame

Baseline

Title

Knee pain as primary study outcome

Description

Time Frame

during intervention: week 2 (acute)

Title

Knee pain as primary study outcome

Description

Time Frame

during intervention: week 10 (acute)

Title

Knee pain as primary study outcome

Description

Time Frame

post-intervention: week 13

Title

Knee pain as primary study outcome

Description

Time Frame

post-intervention: week 26

Title

Knee pain as primary study outcome

Description

Time Frame

post-intervention: week 64

Secondary Outcome Measure Information:

Title

Different subtypes of pain: pain

Description

Pain will be measured using the Visual analogue scale (VAS).

Time Frame

Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)

Title

Different subtypes of pain: intermittent pain

Description

Intermittent pain will be measured using a short and easily applicable self-reported measure, i.e. intermittent and constant pain (ICOAP).

Time Frame

Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)

Title

Different subtypes of pain: constant pain

Description

Constant pain, will be measured using a short and easily applicable self-reported measure, i.e. Intermittent and constant pain (ICOAP).

Time Frame

Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)

Title

Different subtypes of pain: central sensitization

Description

Central sensitization will be measured using an easily applicable self-reported measure i.e. Central Sensitization Inventory (CSI).

Time Frame

Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)

Title

Function in daily living (KOOS subscale)

Description

Time Frame

Baseline, post-intervention (week 13, 26 and 64)

Title

Function in daily living (PGA)

Description

Time Frame

Assessed at baseline and post-intervention (at week 13, 26 and 64)

Title

Treatment adherence

Description

Time Frame

During the intervention (week 1-12) and at week 13

Title

Treatment compliance

Description

Compliance will be calculated as the ratio of the total training duration (recorded in the logbooks) versus the prescribed total training duration, multiplied by 100.

Time Frame

During the intervention (week 1-12) and at week 13

Title

Health care cost effectiveness

Description

Time Frame

Assessed at baseline, at week 13, 26 and 64

Other Pre-specified Outcome Measures:

Title

Pain catastrophizing (explanatory outcome)

Description

Pain catastrophizing will be assessed using the Pain Catastrophizing Scale (PCS-DV).

Time Frame

Assessed at baseline, at week 13, 26 and 64

Title

Pain hypervigilance (explanatory outcome)

Description

Pain hypervigilance will be assessed using the Pain Vigilance and Awareness Questionnaire (PVAQ).

Time Frame

Assessed at baseline, at week 13, 26 and 64

Title

Illness perceptions (explanatory outcome)

Description

Illness perceptions will be assessed using the Illness Perception Questionnaire-revised (IPQ-R).

Time Frame

Assessed at baseline, at week 13, 26 and 64

Title

Dietary intake (explanatory outcome)

Description

Dietary intake will be assessed with the use of the Food Frequency Questionnaire (FFQ).

Time Frame

Assessed at baseline, at week 13, 26 and 64

Title

Inflammation (as treatment mediator)

Description

Inflammation will be tested by a blood-based biomarker panel (e.g. ELISA) for chronic low-grade inflammatory profile.

Time Frame

Assessments will be performed at baseline, during intervention (at week 2 or week 3 and at week 10 or week 11; pre- and post-treatment for the acute effects), at week 13 (at least 48 hours after the last intervention) and at week 64

Title

Endogenous analgesia as treatment mediator: electrical detection threshold

Description

Endogenous pain modulation will be evaluated by determining the electrical detection threshold. Electrical stimulation (Surpass LT Stimulator) will start at 0mA and will be gradually increased until the patient is experiencing a faint sensation.

Time Frame

Assessments will be performed at baseline, during intervention (at week 2 or week 3 and at week 10 or week 11; pre- and post-treatment for the acute effects), and at week 13 (at least 48 hours after the last intervention) and week 64

Title

Endogenous analgesia as treatment mediator: electrical pain threshold

Description

Endogenous pain modulation will be evaluated by determining the electrical pain threshold. Electrical stimulation (Surpass LT Stimulator) will start at 0 mA and will be gradually increased until the patient is experiencing the stimulus as painful.

Time Frame

Title

Endogenous analgesia as treatment mediator: temporal summation

Description

Endogenous pain facilitation will be evaluated by the temporal summation paradigm. Electrical stimuli (Surpass LT Stimulator) will be given at the intensity (mA) of the electrical pain threshold. A verbal numeric rating scale (VNRS) from 0 to 10 will be asked at the first stimulus, at the middle and at the last electrical stimulus.

Time Frame

Title

Endogenous analgesia as treatment mediator: conditioned pain modulation

Description

The efficacy of endogenous analgesia will be evaluated by the conditioned pain modulation paradigm. Conditioned pain modulation will be tested with the electrical stimulator as test stimulus and the cold pressor (12 °C) as conditioning stimulus. The difference between the electrical pain threshold (baseline) and the electrical pain threshold during the cold pressor (baseline + cold pressor) is called the conditioned pain modulation effect. After electrical stimulation (Surpass LT Stimulator), a VNRS score from 0 to 10 will be asked.

Time Frame

Assessments will be performed at baseline, and at week 13 (at least 48 hours after the last intervention) and at week 64.

Title

Endogenous analgesia as treatment mediator: offset-analgesia

Description

Endogenous analgesia will be assessed by offset analgesia. Offset analgesia can be described as the disproportionately large decrease in perceived pain following slight decreases in electrical intensity. Painful electrical stimuli (Surpass LT Stimulator) will be given to the patients into 3 time intervals. The electrical intensity of time interval 1 and 3 will be the same, while the electrical intensity of time interval 2 will be higher. Participants need to report their intensity of pain according to the visual analogue scale ranging from 0 to 10 during the 3 intervals.

Time Frame

Assessments will be performed at baseline and at week 13 (at least 48 hours after the last intervention) and at week 64.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: KOA according to the clinical American College of Rheumatology (ACR) criteria. The clinical ACR criteria for KOA are: knee pain and at least 3 of the 6 following features: age ≥50, morning stiffness <30 minutes, crepitus, bony tenderness, bony enlargement, no palpable warmth. KOA will be confirmed with radiographs, including anterior-posterior (AP) and medio-lateral (ML) radiographs for imaging the tibiofemoral joint, and an axial view for imaging the patellofemoral joint. Kellgren and Lawrence (K&L) grading system for OA will be applied, with K&L grade 2 or higher defined as OA; radiographic KOA is defined as definite osteophytes and possible joint space narrowing. pain, nominated by the patient as 3 /10 or higher on a visual analogue scale on most days of the last 3 months aged ≥ 50 years. Exclusion Criteria: treatment with exercise therapy or joint infiltrations (e.g., corticosteroids, hyaluronic acid) in the preceding 6 months; being on a waiting list for knee replacement; any contra-indication for exercise therapy as established by the treating physician; corticosteroid infiltrations in the last 6 months; cognitive impairment (unable to understand the test instructions and/or Mini Mental State Examination score <23/30); unable to understand the Dutch language; inflammation unrelated to OA (e.g. due to acute or chronic infection) established by CRP>10mg/L. presence of a disorder and/or medication that influences pain and/or the immune system

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ivan Bautmans, PhD

Phone

+3224774207

ivan.bautmans@vub.be

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ivan Bautmans, PhD

Organizational Affiliation

Gerontology department (GERO) and Frailty in Ageing (FRIA) research department, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, B-1090 Brussels, Belgium

Official's Role

Principal Investigator

Facility Information:

Facility Name

Vrije Universiteit Brussel (VUB)

City

Jette

State/Province

Brussels Capital Region

ZIP/Postal Code

1090

Country

Belgium

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ivan Bautmans, PhD

Phone

+3224774207

ivan.bautmans@vub.be

First Name & Middle Initial & Last Name & Degree

Sofie Puts, MSc

First Name & Middle Initial & Last Name & Degree

Lynn Leemans, MSc

First Name & Middle Initial & Last Name & Degree

Laurence Leysen, PhD

First Name & Middle Initial & Last Name & Degree

David Beckwée (prof), PhD

First Name & Middle Initial & Last Name & Degree

Jo Nijs (prof), PhD

First Name & Middle Initial & Last Name & Degree

Ivan Bautmans (prof), PhD

12. IPD Sharing Statement

Plan to Share IPD

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