A Pilot Study to Investigate Biomarkers in Anterior Cruciate Ligament (ACL) Patients and Healthy Controls

Study Overview
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Brief Summary
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Incident rates of ACL rupture are greatest in 16-39 year olds at almost 1 in 1,000. Performance Based Investigations (PBIs) can be used to evaluate and select correct approaches to patient treatment, and biochemical, biomechanical and physiological biomarkers in other conditions are sensitive in distinguishing between disease state severities, type of injuries and responsiveness to treatment. Despite the measurement sensitivity of PBIs, these are not widely used possibly owing to their focus postoperatively where benefits are less worthwhile. This study aims to investigate novel biomarkers as performance based investigations (PBIs) to improve surgical and treatment strategies in anterior cruciate ligament (ACL) patients. The objectives are to identify whether biomarkers, collected before and after operations, can: 1) Assist the surgeon in decision making; 2) Lead to improved prognosis; 3) Be used to predict the outcomes of prognosis, and; 4) Correlate with disease signs/ smoking to help further understand ACL injuries.

Official Title
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A Pilot Study to Investigate Biomarkers in ACL Patients and Healthy Controls

Conditions
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Rupture of Anterior Cruciate Ligament

Intervention / Treatment
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* Procedure: Surgeons knowledge of pre-operative PBIs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: unilateral ACL rupture 18 - 45 years old Exclusion Criteria: combined posterior and ACL rupture multi-ligament instability including medial or lateral collateral ligament injury other lower limb surgery <3mths current significant acute injury affecting other lower extremity joints, or other relevant neurological or musculoskeletal pathology.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Operation - No PBI<br>Patients requiring operation - baseline PBI data not seen by surgeon | |
| Experimental: Operation - PBI available<br>Patients requiring operation - baseline PBI data seen by surgeon pre-operatively | Procedure: Surgeons knowledge of pre-operative PBIs<br>* Surgeon performing ACL repair will have prior knowledge of patients pre-operative PBIs to inform surgical practice<br>|
| No Intervention: Non-operation<br>Patients with ACL rupture not requiring operation | |
| No Intervention: Control<br>Healthy age matched volunteers - No operation | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in knee varus/valgus from baseline to 6 weeks post-ACL reconstruction, measured when performing a single leg squat. |  | Baseline, 6 weeks | 
| The change in knee varus/valgus from baseline to 6 months post-ACL reconstruction, measured when performing a single leg squat |  | Baseline, 6 months | 
| The change in peak vertical ground reaction force from baseline to 6 weeks post-ACL reconstruction, measured when performing a novel isometric task during sitting. |  | Baseline, 6 weeks | 
| The change in peak vertical ground reaction force from baseline to 6 months post-ACL reconstruction, measured when performing a novel isometric task during sitting. |  | Baseline, 6 months | 
| The change in anterior-posterior centre of pressure displacement from baseline to 6 weeks post-ACL reconstruction, measured when performing a 10 second standing balance task. |  | Baseline, 6 weeks | 
| The change in anterior-posterior centre of pressure displacement from baseline to 6 months post-ACL reconstruction, measured when performing a 10 second standing balance task. |  | Baseline, 6 months | 
| The change in time taken to complete a sit-to-stand task, from baseline to 6 weeks post-ACL reconstruction |  | Baseline, 6 weeks | 
| The change in time taken to complete a sit-to-stand task, from baseline to 6 months post-ACL reconstruction |  | Baseline, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in Interleukin-6 obtained from blood samples at baseline to 6 months post-ACL reconstruction |  | 6 months post-ACL reconstruction | 
| The change in Tegner Activity Score from baseline to 6 months post-ACL reconstruction |  | 6 months post-ACL reconstruction | 
| The change in Lysholm Knee Scoring Scale from baseline to 6 months post-ACL reconstruction |  | 6 months post-ACL reconstruction | 
| The change in International Knee Documentation Committee subjective knee evaluation form from baseline to 6 months post-ACL reconstruction |  | baseline to 6 months post-ACL reconstruction | 
| The difference in bone morphogenetic protein-7 (BMP-7) between smokers and non-smokers who undergo ACL reconstruction |  | At time of surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anterior cruciate ligament, Performance based investigations