Biomarkers to inform ACL operations: version-1.0
Research type
Research Study
Full title
An investigation of biomarkers in ACL patients and healthy controls
IRAS ID
82585
Contact name
David R Mullineaux
Contact email
Sponsor organisation
University of Lincoln
Research summary
Summary of Research
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.
Background: Incident rates of ACL rupture are greatest in 16-39 year olds at almost 1-in-1,000. 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 post-operatively where benefits are less worthwhile.
Methods: 45 patients with a suspected ACL rupture recruited from the caseload of a consultant surgeon will be assigned to either: 1) Operation-noPBI (baseline PBI data not seen by surgeon); 2) Operation-yesPBI (baseline PBI seen by surgeon pre-operation), and; 3) Non-operation. A fourth group, 4) control, will be healthy age-matched controls (n=15).
Visits will be: 1) visit-1; 2) operation (groups 1 and 2 only); 3) 6 weeks post-, and; 4) 6 months post-operation/last-visit. At visits 1, 3 and 4 additional procedures will include a small blood draw, and biomechanical and physiological measures to measure lower leg strength and balance. At visit 2, a sample of tissue will be retained and stored anonymously on site at -80C. All blood and tissue samples will be processed together at the end of the study in one batch using a PCR array for cytokines/integrins, selectins, cell-adhesion molecule family members (e.g. IL-6), and other genes important to cell adhesion and cytoskeleton bridging (e.g. catenins).
Summary of Results
Balance data were collected for eight anterior-cruciate ligament (ACL) injured participants before and after surgery, and 45 uninjured controls. Both linear and non-linear analyses of the centre of pressure (CoP) balance data were performed. For linear measures, there was no statistical significance difference (p>0.05) between the involved and comparison limbs (mean±SD pre-surgery CoP path length; ACL involved: 76±19 cm; ACL uninvolved: 87±27 cm; uninjured controls: 93±28 cm) or after surgery (19 weeks post-surgery; ACL involved: 79±27 cm). For non-linear measures, ACL injury was related to the ACL involved pre-surgery mediolateral complexity index (4.9±1.3) being significantly less than uninjured controls (6.0±0.9), but this complexity being restored at 19 weeks post surgery (ACL involved: 5.9±1.0). The findings provide new evidence to support that ACL injury results in a loss of complexity and that the multiscale sample entropy of the CoP may provide an insight into the changes in lower limb biomechanics that occur due to ACL injury and reconstructive surgery. Further research is required to understand the role of complexity on functional movement, and to assess more fully if complexity is clinically useful.
REC name
East Midlands - Derby Research Ethics Committee
REC reference
14/EM/1130
Date of REC Opinion
12 Sep 2014
REC opinion
Further Information Favourable Opinion