Clinical trial NCT03473873: Protective Role of Muscle Function for Early Features of Knee Osteoarthritis After Anterior Cruciate Ligament Injury
Official title: Is Good Muscle Function a Protective Factor for Early Features of Knee Osteoarthritis After Anterior Cruciate Ligament Injury (SHIELD)? A Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Knee Osteoarthritis
Anterior Cruciate Ligament Injury
Osteoarthritis, Knee
Muscle Weakness
Lead sponsor: Lund University
Sponsor class: OTHER
Collaborators: name: Oslo University Hospital
First posted: 2018-03-22
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be recruited from the Department of Orthopedics, Skåne University Hospital, Sweden and the Department of Orthopedics, Ullevål Hospital, Oslo, Norway. The majority of patients (approx. 80%) will be included in Sweden.

Non-injured controls will be recruited among students at Lund University, Lund, Sweden.

Brief summary: In this longitudinal prospective cohort study including young people with anterior cruciate ligament reconstruction (ACLR), the aims are to 1) study the association between different measures of muscle function and early future of knee osteoarthritis (OA) assessed as patient-reported pain, 2) explore potential associations between muscle function and features indicative of early radiographic OA measured with MRI, and early detection of OA in biomarker profiles, respectively, 3) monitor the patients' functional status, and early OA development over time and 4) investigate the prevalence of early knee OA in individuals 1 and 3 years post ACLR, respectively, compared to non-injured controls.The main hypothesis is that knee extensor weakness predicts future symptomatic OA of the knee (KOOS pain).

Detailed description: This is a longitudinal, prospective, cohort study. The reporting will adhere to the STROBE guidelines. Approximately 100 patients 12 months (range 10 - 16 months) after anterior cruciate ligament reconstruction (ACLR) will be recruited from Skåne University Hospital, Sweden and Ullevål Hospital, Oslo, Norway. The majority of the patients (approx. 80 %) will be recruited in Sweden. As a sample of convenience, 20 age- and sex-matched non-knee injured individuals will be recruited among students in Lund, Sweden.

A research coordinator at each site will determine eligibility for the study, based on pre-specified inclusion and exclusion criteria. Patients will be provided with written and oral information about the study. Patients who accept to participate will be assessed with various measures of muscle function, patient-reported outcomes, MRI, and blood samples for biomarker analyses, at baseline (1 year after ACLR) and 2 years later (3 years after ACLR).

For descriptive purposes, the mean difference (95% CI), or median (quartiles), between baseline and follow-up assessments will be used as appropriate. Separate linear regression model will be used to elucidate the influence of change in each muscle function variable on change in primary, secondary and exploratory outcomes (biomarkers), adjusted for baseline values. Separate linear regression models will also be used to elucidate the influence of demographic factors on change in muscle function, self-reported outcomes, and early OA. Assuming a clinically relevant correlation of 0.30 between knee extension strength and self-reported pain, 84 patients are needed with 80% power at the 5% significance level. Based on this calculation, 100 patients will be included, including an approximate drop-out of 15%. For explorative purposes, an analysis of covariance (ANCOVA) will be used to investigate differences in the presence of early knee OA between the 100 patients with ACLR and twenty sex and age matched non-injured individuals, adjusting for activity level.

Eligibility criteria: Inclusion Criteria patients:

* One year after ACL reconstruction (ACLR)
* With or without associated injuries to other structures of the knee (e.g., collateral ligament(s), meniscal injury)
* Age 18-35 years

Inclusion Criteria controls:

* Age 18-35 years
* No previous injuriy or surgery to either knee

Exclusion Criteria:

* Less than 10 months after ACLR
* More than 16 months after ACLR
* Injury or surgery to other knee (e.g., ACL, meniscal)
* Previous knee surgery index knee
* Previous serious knee injury index knee resulting in pain, swelling, and/or requiring inpatient or outpatient health care (e.g., ACLR, meniscus, patella luxation)
* Diseases or disorders overriding the knee condition (e.g., neurological disease)
* Contraindications for MRI
* Not understanding the languages of interest (any Scandinavian language or English)

Primary outcomes:
measure: Patient-reported pain
timeFrame: Change from baseline to 2-year follow up
Secondary outcomes:
measure: Compositional MRI (T2 relaxation time and 3DPD)
timeFrame: Change from baseline to 2-year follow up
Other outcomes:
measure: Biomarkers
timeFrame: Change from baseline to 2-year follow up
Locations:
city: Oslo
country: Norway
facility: May Arna Risberg
city: Lund
country: Sweden
facility: Eva Ageberg
Study officials:
affiliation: Department of Health Sciences, Lund University, PO Box 157, 221 00 Lund, Sweden
name: Eva Ageberg, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oslo University Hospital, Division of Orthopedic Surgery, PO.Box 4956 Nydalen, 0424 Oslo, Norway
name: May Arna Risberg, PhD
role: PRINCIPAL_INVESTIGATOR
References: