Study of Autologous Conditioned Serum After Anterior Cruciate Ligament Reconstructive Surgery

Study Overview
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Brief Summary
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Abstract Background Pro-inflammatory cytokines play a pivotal role in osteoarthritis, as well as in bone tunnel widening after ACL reconstructive surgery. A new treatment option is to administer autologous conditioned serum (ACS) containing endogenous anti-inflammatory cytokines including IL-1Ra and growth factors (IGF-1, PDGF and TGF-ß1, among others) in the liquid blood phase. Objective The purpose of this trial was to establish whether the osteoclastic effect could be affected by intra-articular application of ACS, thus resulting in a potential decrease of knee laxity and leading to a better postoperative outcome. Methods In a prospective, randomized, double-blinded, placebo-controlled trial with two parallel groups, 62 patients were treated. Bone tunnel width was measured by CT scans, while clinical efficacy was assessed by patient-administered outcome instruments (WOMAC, IKDC 2000) up to one year following the ACL reconstruction in patients receiving either ACS (Group A) or placebo (Group B). The investigators compared the levels and dynamics of IL-1b concentrations in the synovial liquid and examined the correlation between the levels of IL-1b at three different post-operative points. Level of evidence Therapeutic study, Level 1 (randomized controlled trial [significant differences and narrow confidence intervals])

Official Title
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Intraarticular Application of Autologous Conditioned Serum (ACS/Orthokine) Reduces Bone Tunnel Widening After ACL Reconstructive Surgery A Prospective, Randomized, Saline-controlled, Patient- and Observer-blinded, Parallel-design Trial

Conditions
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Joint Instability

Intervention / Treatment
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* Procedure: ACL reconstructive surgery and ACS/ Orthokin application


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible patients were: older than 18 years prior to each surgery, traumatic ACL rupture was determined on the basis of a clinical examination and confirmed by exploratory and therapeutic arthroscopic surgery in accordance with good surgical practice the same preoperative diagnosis of isolated ACL rupture a knee axis deviation up to 5°; knee osteoarthritis up to grade 1 according to the AO knee chondral lesion up to grade 2 (Outerbridge classification). Exclusion Criteria: poor general health as judged by the orthopedic surgeon Concomitant painful or disabling disease of the spine, hips, or lower limbs that would interfere with evaluation of the afflicted knee Any clinically significant or symptomatic vascular or neurological disorder; crystalline, inflammatory and infectious arthropathies Infections Osteomyelitis Alcohol/drug abuse Known coagulopathy Corticosteroid or anti-coagulant usage, and morbid obesity.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ACS - Orthokin<br>Autologous conditioned serum (ACS) - Orthokin containing endogenous anti-inflammatory cytokines including IL-1Ra and growth factors (IGF-1, PDGF and TGF-ß1, among others) in the liquid blood phase. | Procedure: ACL reconstructive surgery and ACS/ Orthokin application<br>* ACL reconstructive surgery and ACS/ Orthokin or Placebo intraarticular application on Day 0,1,6 and 10 postoperatively, regarding the Arm<br>|
| Placebo Comparator: Placebo<br>Physiologic solution | Procedure: ACL reconstructive surgery and ACS/ Orthokin application<br>* ACL reconstructive surgery and ACS/ Orthokin or Placebo intraarticular application on Day 0,1,6 and 10 postoperatively, regarding the Arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone tunnel width - CT scans. Clinical efficacy - patient administered outcome instruments (WOMAC, IKDC 2000). |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurements and correlation between the levels of synovial fluid IL-1b at three different post-operative points. |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ACL reconstruction, autologous conditioned serum, Orthokine, osteoarthritis, interleukin receptor antagonist, growth factors, WOMAC, IKDC