Clinical trial NCT06391554: Effects of EDUcation and EXercise Compared to Education Alone on Clinical and Physiological Outcomes in Patients With Hip Osteoarthritis
Official title: Effects of EDUcation and EXercise Compared to Education Alone on Clinical and Physiological Outcomes in Patients With Hip Osteoarthritis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hip Osteoarthritis
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
name: Regionshospitalet Silkeborg
name: Vejle Hospital
name: Physiotherapy Associates
First posted: 2024-04-30
Enrollment: 150
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The EDUEX trial will determine whether the addition of progressive resistance training (PRT) to a patient education program (EDU) will improve clinical outcomes in patients with hip OA.

In a subsample, the effect of PRT on the articular cartilage and other structures of the hip joint is investigated. In this subsample, a comprehensive assessment of possible mechanisms underlying the effects of exercise on pain and function is undertaken.

The EduEx trial will be a multicentre, stratified (by site), block randomized (allocation 1:1), controlled, parallel-group superiority trial. 150 people with hip OA will be recruited from hospitals, physiotherapy clinics, social media and newspapers. Participants will be randomized to PRT and EDU or EDU alone. All 150 participants will be included in the clinical evaluation study (CLIN). The last 40 participants randomized to PRT+EDU and to EDU, respectively, will also be included in the mechanistic (MECH) evaluation study (n=80), by being asked to participate in additional outcome assessments. The primary endpoint will be the 12 months follow-up for both the CLIN and MECH study, while a secondary endpoint will be the 3-month follow-up.

Detailed description: DESIGN

The EduEx trial will be a multicentre, stratified (by site), block randomized (allocation 1:1), controlled, parallel-group superiority trial. 150 people with hip OA will be recruited from the Orthopedic Departments at hospitals and from physiotherapy clinics, social media and newspapers. Participants will be randomized to PRT+EDU or EDU.

All 150 participants will be included in the clinical evaluation study (CLIN) while only the last 40 participants randomized to PRT+EDU and EDU, respectively, will also be included in the mechanistic evaluation study (MECH, n=80), by being asked to participate in additional outcome assessments including magnetic resonance imaging of the hip.

The primary endpoint will be the 12 months follow-up for both the CLIN and MECH study, while the secondary endpoint will be the 3-month follow-up.

RANDOMIZATION

After baseline assessment, participants will be randomized in a 1:1 ratio to PRT+EDU or EDU. A computer-generated list of random numbers will be generated in the Research Electronic Data Capture (REDCap) system. The randomization will be stratified by site and block randomized, to ensure equal distribution of allocations among trial sites. Two lists of random numbers will be generated, one for the first 70 participants and one for the last 80 participants recruited, to enable an even distribution of treatment allocation of the 80 participants in the MECH subsample. Treatment allocation will be concealed as one of the principal investigators will use the randomization tool only after the baseline assessment has been performed.

INTERVENTIONS

The PRT and EDU interventions will be conducted either at the collaborating hospital departments or physiotherapy clinics across Denmark.

PRT: Participants allocated to receive PRT will attend 3 months of supervised PRT followed by 9 months of unsupervised PRT with the addition of 8 exercise booster sessions. The PRT program consists of two weekly training sessions (60 min per session) with ≥48 hours of rest between sessions. All supervised PRT sessions will be group-based (up to 5 participants) supervised by one physiotherapist.

EDU: Both treatment arms will attend three EDU sessions provided by a trained physiotherapist involving important disease-specific information. The sessions will address knowledge of OA, treatment options with a specific focus on physical activity recommendations, advice on self-management and more. All three sessions will emphasize on engaging the participants actively and sharing experiences with each other.

STATISTICAL ANALYSIS PLAN

The analyses will be based on the between-group difference in change in the primary and secondary outcomes from baseline to the 12 months follow-up, according to the intention-to-treat (ITT) principle. Additionally, per protocol analyses will be performed including only participants with high adherence to the EDU sessions (at least 2 sessions attended) and high adherence to the exercise sessions (≥80% of the planned sessions completed) and high exercise fidelity (≥80% of prescribed repetitions performed). Between-group comparisons of change from baseline to follow-up in the primary and secondary continuous outcomes will be analysed using a repeated measures mixed model with participants and sites as random effects and with visits and treatment arm as fixed effects.

DATA MANAGEMENT

All data and outcomes collected from participants will be entered into the REDCap database. For the patient reported outcomes, participants will fill out questionnaires directly into REDCap. If a participant is unable to do so, they will fill out paper versions of the questionnaires and the tester will enter it into REDCap and shred the paper versions. The data will be maintained in storage for five years after trial termination.

PATIENT AND PUBLIC INVOLVEMENT

In the EduEx trial we have established an advisory board of four patients with hip osteoarthritis and a physiotherapists. Patients and physiotherapists have been invited to participate in the board throughout the research project. The board have and will continue to influence clinical outcomes, practicalities, and content of the interventions. The board will have one meeting every three months during the planning, conducting and dissemination processes of the trial and will give advice (consultation level of involvement) throughout.

ETHICAL CONSIDERATIONS

The study intervention is non-invasive and is expected to result in a generally optimized health status of the included participants. Approval from the Central Denmark Region Committee on Health Research has been obtained for the EduEx trial. Written informed consent will be obtained from all participants prior to inclusion and the project will be performed in accordance with the Helsinki Declaration. Authorship eligibility will be based on the recommendations from The International Committee of Medical Journal Editors. Any important protocol amendments for The EduEx trial will be registered at ClinicalTrial.gov and reported to the Central Denmark Region Committee on Health Research.

RESEARCH RESULTS

The results from this trial will be published in peer-reviewed scientific journals and presented at congresses, regardless of whether the results are inconclusive, negative or positive.

There are 3 preplanned studies to be conducted on the results from this trial that will be reported in 3 separate research papers:

1. The primary clinical evaluation study (CLIN) comparing effects of PRT+EDU and EDU alone on the primary outcome of HOOS ADL is study number one.
2. The primary mechanistic evaluation study (MECH) comparing PRT+EDU and EDU alone on changes in hip joint tissue is study number two.
3. A secondary MECH evaluation study (MECH2) is study number three, in which the mechanisms of exercise are investigated by looking at associations of changes in other outcomes with the changes seen for hip pain and physical function.

Eligibility criteria: Inclusion Criteria:

* Clinically diagnosed with hip OA according to the criteria by the National Institute for Health and Care Excellence (NICE)
* Radiographic verification of hip OA diagnosis with Kellgren Lawrence score of 2 or 3 in one or both hips
* Not scheduled for a total hip replacement within the following 12 months
* An event of hip pain every day of at least 3 out of 10 on a numerical rating scale during the last 14 days
* Age ≥ 45 years
* Adequacy in written and spoken Danish

Exclusion Criteria:

* Comorbidity that markedly influences hip function or degeneration of tissue in or around the hip joint (rheumatic, neurological, mental or other)
* Surgery in the lower extremities within the six months prior to inclusion
* BMI \> 40
* Pregnancy
* Resistance exercise (weights or elastic bands) for the lower extremities exceeding 12 sessions over the last 6 months or 6 sessions over the last 3 months
* Suffering from claustrophobia or not tolerating whole body MRI scanner
* Metallic implants from the waist to just above the knee
* Pacemaker or other medical devices that are not MR approved

Primary outcomes:
measure: Changes from baseline to 12 month follow-up (primary endpoint) in the Hip Disability and Osteoarthritis Outcome Score (HOOS) ADL function subscale
timeFrame: Measured at baseline, 12 weeks and 12 month follow-up
measure: Changes from baseline to 12-month follow-up (primary endpoint) in the hip articular cartilage of the index hip measured by MRI T2 relaxation time mapping.
timeFrame: Measured at baseline and 12 month follow-up
measure: Changes from baseline to 12-month follow-up (primary endpoint) in the articular cartilage of the index hip measured by MRI T1rho relaxation time mapping.
timeFrame: Measured at baseline and 12 month follow-up
Secondary outcomes:
measure: Changes in the Scoring Hip Osteoarthritis with MRI (SHOMRI) semiquantitative scoring system for evaluating imaging features relevant to the severity and progression of osteoarthritis
timeFrame: Measured at baseline and 12 month follow-up
measure: Change in the HOOS Pain subscale
timeFrame: Measured at baseline, 12 weeks and 12 month follow-up
measure: Change in the HOOS Hip-related Quality of Life subscale
timeFrame: Measured at baseline, 12 weeks and 12 month follow-up
measure: Change in the HOOS Symptoms subscale
timeFrame: Measured at baseline, 12 weeks and 12 month follow-up
measure: Change in the HOOS Sport/recreation subscale
timeFrame: Measured at baseline, 12 weeks and 12 month follow-up
measure: Change in the 30 second chair stand test
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Change in the 9-step stair climb test
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Change in the 40 meter fast-paced walk test
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Number of treatment responders according to OMERACT-OARSI response criteria
timeFrame: Measured at 12 weeks and 12 month follow-up
Other outcomes:
measure: Demographic data consisting of sex, age, weight, height, BMI, analgesics, cohabiting status, marital status, employment status, alcohol intake, smoking habits, duration and severity of symptoms, current and previous treatment, co-morbidities.
timeFrame: Measured at baseline (treatment received, weight, co-morbidities, and analgesic use is also measured at 12 weeks and 12 month follow-up
measure: Safety outcomes will include number of adverse events and serious adverse events (SAE)
timeFrame: Recorded throughout the trial (up to 1 year)
measure: Participants who drop out from the trial
timeFrame: Recorded throughout the trial (up to 1 year)
measure: Adherence to PRT exercise program
timeFrame: Recorded throughout the trial (up to 1 year)
measure: Adherence to EDU sessions
timeFrame: Recorded throughout the trial (up to 1 year)
measure: Fidelity to the PRT exercise program
timeFrame: Recorded throughout the trial (up to 1 year)
measure: Patient expectations for treatment modalities
timeFrame: Measured at baseline
measure: Patient preferred treatment option
timeFrame: Measured at baseline
measure: Change in the Pain Catastrophizing Scale
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Change in the Hospital Anxiety and Depression Scale
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Number of painful sites on a region-divided body chart
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Change in dietary pattern measured by the danish "Hjertekost" questionnaire
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Patient-reported Global Perceived Effect
timeFrame: Measured at 12 weeks, and 12 month follow-up
measure: Patient-reported Treatment Failure of the interventions
timeFrame: Measured at 12 weeks, and 12 month follow-up
measure: Change in the Self-Efficacy for Managing Chronic Disease 6-item Scale
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Change in the Pittsburgh Sleep Quality Index
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Changes in physical activity level measured by accelerometry
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Treatment response according to the Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) criteria
timeFrame: Measured at 12 weeks, and 12 month follow-up
measure: Changes in pain sensitivity using quantitative sensory testing by a computer-controlled cuff algometer.
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Changes in pain tolerance thresholds using quantitative sensory testing by a computer-controlled cuff algometer.
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Changes in temporal summation using quantitative sensory testing by a computer-controlled cuff algometer.
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Changes in conditioned pain modulation using quantitative sensory testing by a computer-controlled cuff algometer.
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Changes in maximal voluntary isometric contraction by Isokinetic dynamometry. Assessed for hip flexors and extensors, and knee flexors and extensors.
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Changes in rate of force development by Isokinetic dynamometry. Assessed for hip flexors and extensors, and knee flexors and extensors.
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Changes in maximal voluntary muscle activation using the interpolation twitch technique.
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Changes in anatomical cross-sectional area of m. Quadriceps, Gluteus Maximus and Gluteus Medius measured by MRI cross-sectional area
timeFrame: Measured at baseline and 12 month follow-up
measure: Changes in extramyocellular infiltrations of fat and connective tissue of m. Quadriceps, Gluteus Maximus and Gluteus Medius measured by MRI cross-sectional area
timeFrame: Measured at baseline and 12 month follow-up
measure: Changes in bone mineral density measured by Dual energy xray absorptiometry
timeFrame: Measured at baseline and 12 month follow-up
measure: Changes in muscle mass measured by Dual energy xray absorptiometry
timeFrame: Measured at baseline and 12 month follow-up
measure: Changes in fat mass measured by Dual energy xray absorptiometry
timeFrame: Measured at baseline and 12 month follow-up
measure: Changes in concentrations of blood serum biomarkers for low grade systemic inflammation, cartilage degradation, cartilage formation, bone degradation, and synovial inflammation.
timeFrame: Measured at baseline and 12 month follow-up
measure: Changes in hip pain assessed by a numerical rating scale from 0-10 (0 = no pain, 10 = worst imaginable pain)
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Changes in One-legged 30 second chair stand test measured for index leg and contralateral leg
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Changes in indirectly measured VO2max by the Åstrands submaximal cycle test
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Changes in patients global assessment of impact of osteoarthritis
timeFrame: Measured at baseline, 12 weeks, and 12 month follow-up
measure: Patient Acceptable Symptom State (PASS)
timeFrame: Measured at 12 weeks and 12 month follow-up
Locations:
city: Aarhus C
country: Denmark
facility: Aarhus University
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital
Study officials:
affiliation: Aarhus University Hospital
name: Troels Kjeldsen, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Aarhus University Hospital
name: Thomas Frydendal, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Aarhus University Hospital
name: Inger Mechlenburg, Prof.
role: STUDY_DIRECTOR
affiliation: University of Aarhus
name: Ulrik Dalgas, Prof.
role: STUDY_DIRECTOR
References: