Protective Role of Muscle Function for Early Features of Knee Osteoarthritis After Anterior Cruciate Ligament Injury (SHIELD)

Is Good Muscle Function a Protective Factor for Early Features of Knee Osteoarthritis After Anterior Cruciate Ligament Injury (SHIELD)? A Prospective Cohort Study

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).

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis; Osteoarthritis, Knee; Muscle Weakness; Anterior Cruciate Ligament Injury
• Intervention / Treatment: Other: Measures of muscle function

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.

• Study Type: Observational
• Enrollment (Actual): 106

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0424
    • May Arna Risberg
• Sweden
  • Lund, Sweden, 22100
    • Eva Ageberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

SHIELD; Patients with anterior cruciate ligament injury

Other: Measures of muscle function; The participants will be assessed with various measures of muscle function at baseline and at follow up including: Isokinetic knee muscle strength, Isometric strength of trunk and lower extremity, single-leg hop for distance (SLHD), side hop, postural orientation errors (single leg-squat, stair descending, forward lunge, SLHD), hip and ankle range of motion, and muscular activation patterns.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported pain	Knee Osteoarthritis Outcome Score (KOOS) subscale pain	Change from baseline to 2-year follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compositional MRI (T2 relaxation time and 3DPD)	Compositional MRI, a proxy for early morphological degeneration of joint structures. Quantitative morphology of cartilage quality will be made using T2 mapping, to measure collagen orientation changes within the cartilage, and bone shape (3DPD)	Change from baseline to 2-year follow up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers	Blood samples of venous blood will be collected to assess molecular biomarkers of cartilage turnover in serum. Specific biomarkers including, but not limited to, Cartilage oligomeric matrix protein (COMP), will be measured	Change from baseline to 2-year follow up

Collaborators and Investigators

• Sponsor: Lund University
• Collaborators: Oslo University Hospital
• Investigators: Principal Investigator: Eva Ageberg, PhD, Department of Health Sciences, Lund University, PO Box 157, 221 00 Lund, Sweden; Principal Investigator: May Arna Risberg, PhD, Oslo University Hospital, Division of Orthopedic Surgery, PO.Box 4956 Nydalen, 0424 Oslo, Norway

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2018
• Primary Completion (Actual): July 1, 2023
• Study Completion (Actual): July 1, 2023

Study Registration Dates

• First Submitted: March 9, 2018
• First Submitted That Met QC Criteria: March 21, 2018
• First Posted (Actual): March 22, 2018

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Leg Injuries; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Muscular Diseases; Neuromuscular Manifestations; Knee Injuries; Osteoarthritis; Osteoarthritis, Knee; Muscle Weakness; Wounds and Injuries; Anterior Cruciate Ligament Injuries
• Other Study ID Numbers: 2016/319

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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