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

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

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.

Study Overview

• Status: Completed
• Conditions: Rupture of Anterior Cruciate Ligament
• Intervention / Treatment: Procedure: Surgeons knowledge of pre-operative PBIs

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Lincolnshire
    • Lincoln, Lincolnshire, United Kingdom, LN2 5QY
      • United Lincolnshire Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: United Lincolnshire Hospitals NHS Trust
• Collaborators: University of Lincoln
• Investigators: Principal Investigator: Prof David Mullineaux, PhD, University of Lincoln

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 5, 2015
• Primary Completion (ACTUAL): May 20, 2022
• Study Completion (ACTUAL): May 20, 2022

Study Registration Dates

• First Submitted: October 23, 2014
• First Submitted That Met QC Criteria: November 20, 2014
• First Posted (ESTIMATE): November 24, 2014

Study Record Updates

• Last Update Posted (ACTUAL): May 27, 2022
• Last Update Submitted That Met QC Criteria: May 23, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Anterior cruciate ligament; Performance based investigations
• Additional Relevant MeSH Terms: Wounds and Injuries; Rupture
• Other Study ID Numbers: 120614Mullineaux