Natural Course and Recovery After ACL-injury (NACOX)

The natural course after ACL injury is not well described in the literature. Every year about 7000 people, a majority aged 15-30 years old, injure their anterior cruciate ligament (ACL) in Sweden. About 3500 go through surgical treatment and rehabilitation. Despite the large amount of research on ACL-injuries, there are still many patients who have unsatisfactory outcomes regarding instability, decreased activity level, and quality of life, not being able to return to sport as well as an increased risk for osteoarthritis. The general aim of the study is to evaluate the natural course and recovery after ACL injury. Specific aims:

• To evaluate physical, psychological and contextual factors affecting recovery after anterior cruciate ligament (ACL) injury. Recovery is related both to natural course and to treatment chosen
• To evaluate factors affecting the decision for which treatment to choose (ACL reconstruction and rehabilitation or rehabilitation alone)
• To evaluate factors affecting the decision for return to sports
• To study development of knee osteoarthritis after ACL-injury
• To study epidemiology of acute knee trauma
• To study risk factors for new injuries after ACL-injury These aims will be pursued by consequently and prospectively following patients who sustain a new ACL injury in a multicenter study including approximately 800 patients. Assessment methods will be questionnaires to patients, orthopedic doctors and physical therapists. A sub-cohort of 130 patients will undergo multiple clinical and functional examination as well as MRIs and blood, urine and joint fluid samples.

Study Overview

• Status: Active, not recruiting
• Conditions: Anterior Cruciate Ligament Injury
• Intervention / Treatment: Other: Rehabilitation; Procedure: ACL reconstruction

Detailed Description

Study design: A descriptive and prospective prognostic cohort study, with consecutive recruitment of patients during a 12 month period from seven sites in Sweden Start of recruiting participants is October 2016. Most participants will receive a diagnosis from an orthopedic doctor approximately 2-4 weeks after their knee injury, and undergo rehabilitation for at least the first three months, before a decision regarding ACL reconstruction is taken (in line with current treatment guidelines). The patient cohort will be naturally divided into reconstruction plus rehabilitation, and rehabilitation only. Being included in the study will not affect the choice of treatment.

Patients will be asked to participate at their initial contact with healthcare, after their knee injury. The recruitment process will differ slightly between the different sites, based on the clinical routine.

Patients who accept to participate will complete web-based questionnaires distributed via smart phones or e-mail, once a week the first 6 weeks, every second week up to 3rd month, every month up to 1 year and every second month up to 3 years after initial injury. The length of the questionnaires varies from very short (approximately 10 questions that take 2 minutes to fill in) to longer at specific critical time points. Each time the patient has contact with an orthopedic surgeon, the patient, orthopedic doctor and physiotherapist (if the patient has contact with one) will be asked to answer a questionnaire about choice of treatment (surgery or not). In addition, when the patient reports that they are back to sport activity, the patient and the physiotherapist will be asked to answer a questionnaire about the decision to return to sport. Patients who will have ACL reconstruction will be followed up with new baseline from the time of reconstruction.

Patients recruited from Linköping will have expanded follow-up data collection at baseline and 3, 6, 12 and 24 months after injury. At these follow-ups, a clinical examination will be completed by an orthopedic surgeon or physiotherapist, MRI, and blood and urine samples will be collected. A joint fluid sample will be acquired at baseline, and at the time of ACL reconstruction (if the patient has surgical treatment). Radiographs will be done at baseline and 5 years follow up. Patients who have ACL reconstruction will be followed up with new baseline at the time for reconstruction, but without MRI or blood and urine samples.

• Study Type: Observational
• Enrollment (Actual): 275

Contacts and Locations

• Study Contact: Name: Joanna Kvist, Professor; Phone Number: +46 13 284664; Email: joanna.kvist@liu.se

Study Locations

• Sweden
  • Ostergotland
    • Linkoping, Ostergotland, Sweden, 58183
      • Linköping University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with ACL-injury from 7 different sites in Sweden

Description

Inclusion Criteria:

• Patients with a knee injury (ACL injury)
• Age at time of ACL injury: 15-40 years

Exclusion Criteria:

• ACL injury/ACL reconstruction on the same knee
• Serious knee injuries to the injured knee, ex fracture that require separate treatment
• ACL injury more than 6 weeks ago
• Inability to understand written and spoken Swedish language
• Cognitive impairments
• Other illness/injury that impairs function (e.g. fibromyalgia, rheumatic diseases and other diagnosis that causes chronic pain)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ACL injury; Patients with an acute (not more than 6 weeks old) anterior cruciate ligament (ACL) injury	Other: Rehabilitation; In line with current treatment guidelines, patients will undergo rehabilitation for at least the first three months, before a decision regarding ACL reconstruction is taken
ACL reconstruction; Some of the patients with ACL injury will have reconstruction of the ACL. These will be followed as a new group.	Other: Rehabilitation; In line with current treatment guidelines, patients will undergo rehabilitation for at least the first three months, before a decision regarding ACL reconstruction is taken; Procedure: ACL reconstruction; Approximately half of the patients will have ACL-reconstruction after an initial time of rehabilitation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Return to physical activity/ sports	Patients report when they are back to unrestricted physical activity or sports	1 year
Knee function, IKDC	The IKDC subjective knee evaluation form is a self-administered questionnaire which contains 18 items divided into 3 subgroups. These subgroups are symptoms, sports and daily activities and the patients current and previous levels of knee function.	1 year
Osteoarthritis	Development of osteoarthritis examined with x-rays at 5 years	5 years
New injuries	Reported new knee injuries	3 years
Factors related to treatment choice	Questionnaires to patients, orthopedic surgeon and physical therapist about the treatment decision	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychological factors affecting recovery	Include questionnaires about motivation, goals, satisfaction, self efficacy, fear for new injury, readiness for return to sports, expectations	2 years
Physical factors affecting recovery, Range of motion	Measured with goniometer	1 year
IKDC	The IKDC subjective knee evaluation form is a self-administered questionnaire which contains 18 items divided into 3 subgroups. These subgroups are symptoms, sports and daily activities and the patients current and previous levels of knee function.	2 years
Physical factors affecting recovery, gait	Qualitativ assessment of gait pattern	4 weeks
Physical factors affecting recovery, muscle strength	Measured with the Biodex dynamometer, peak torque at 60 degrees per second	6 months
Physical factors affecting recovery, functional performance	Measured with hop tests, evaluated with the LSI (limb symmetry index)	6 months
Physical factors affecting recovery, functional performance	Measured with hop tests, evaluated with the LSI (limb symmetry index)	1 year

Collaborators and Investigators

• Sponsor: Linkoeping University
• Investigators: Principal Investigator: Joanna Kvist, Professor, IMH Linkoping University, Sweden

Publications and helpful links

General Publications

• Sonesson S, Kvist J. Bilateral changes in knee joint laxity during the first year after non-surgically treated anterior cruciate ligament injury. Phys Ther Sport. 2022 Nov;58:173-181. doi: 10.1016/j.ptsp.2022.10.011. Epub 2022 Oct 26.
• Casula V, Tajik BE, Kvist J, Frobell R, Haapea M, Nieminen MT, Gauffin H, Englund M. Quantitative evaluation of the tibiofemoral joint cartilage by T2 mapping in patients with acute anterior cruciate ligament injury vs contralateral knees: results from the subacute phase using data from the NACOX study cohort. Osteoarthritis Cartilage. 2022 Jul;30(7):987-997. doi: 10.1016/j.joca.2022.02.623. Epub 2022 Apr 11.
• Filbay S, Kvist J. Fear of Reinjury Following Surgical and Nonsurgical Management of Anterior Cruciate Ligament Injury: An Exploratory Analysis of the NACOX Multicenter Longitudinal Cohort Study. Phys Ther. 2022 Feb 1;102(2):pzab273. doi: 10.1093/ptj/pzab273.
• Grevnerts HT, Sonesson S, Gauffin H, Ardern CL, Stalman A, Kvist J. Decision Making for Treatment After ACL Injury From an Orthopaedic Surgeon and Patient Perspective: Results From the NACOX Study. Orthop J Sports Med. 2021 Apr 15;9(4):23259671211005090. doi: 10.1177/23259671211005090. eCollection 2021 Apr.
• Kvist J, Gauffin H, Tigerstrand Grevnerts H, Ardern C, Hagglund M, Stalman A, Frobell R. Natural corollaries and recovery after acute ACL injury: the NACOX cohort study protocol. BMJ Open. 2018 Jun 27;8(6):e020543. doi: 10.1136/bmjopen-2017-020543.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: October 9, 2016
• First Submitted That Met QC Criteria: October 10, 2016
• First Posted (Estimated): October 12, 2016

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Leg Injuries; Knee Injuries; Wounds and Injuries; Anterior Cruciate Ligament Injuries
• Other Study ID Numbers: NACOX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO