Study of Autologous Conditioned Serum After Anterior Cruciate Ligament Reconstructive Surgery

Joint Instability Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01037738
• Other study ID #: REC LCA 2B
• Status: Completed
• Phase: Phase 1
• First received: December 3, 2009
• Last updated: December 22, 2009
• Start date: May 2006
• Est. completion date: January 2009

Study information

• Verified date: January 2009
• Source: University of Zagreb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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])

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: January 2009
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Joint Instability

Intervention

Procedure:
• ACL reconstructive surgery and ACS/ Orthokin application
ACL reconstructive surgery and ACS/ Orthokin or Placebo intraarticular application on Day 0,1,6 and 10 postoperatively, regarding the Arm

Locations

Country	Name	City	State
Croatia	Medical School, University of Zagreb	Zagreb

Sponsors (2)

Lead Sponsor	Collaborator
University of Zagreb	Croatian Institute of Health Insurance

Country where clinical trial is conducted

Croatia, 

References & Publications (1)

References 1. Harris NL, Indelicato PA, Bloomberg MS, Meister K, Wheeler DL. Radiographic and histologic analysis of the tibial tunnel after allograft anterior cruciate ligament reconstruction in goats. American Journal of Sports Medicine 30 (3):368-73,2002. 2. Hoher J, Moller HD, Fu FH. Bone tunnel enlargement after anterior cruciate ligament reconstruction: fact or fiction? Knee Surgery, Sports Traumatology and Arthroscopy 6 (4):231-40,1998. 3. Hsu CJ, Hsu HC, Jim YF. A radiological study after anterior cruciate ligament reconstruction. Journal of Chinese Medical Association 66(3):160-5,2003. 4. Nakayama Y, Shirai Y, Narita T, Mori A. Enlargement of bone tunnels after anterior cruciate ligament reconstruction. Nippon Ika Daigaku Zasshi 65(5):377-81,1998. 5. Topliss C, Webb J. An audit of tunnel position in anterior cruciate ligament reconstruction. Knee 8(1):59-63,2001.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone tunnel width - CT scans. Clinical efficacy - patient administered outcome instruments (WOMAC, IKDC 2000).		1 year
Secondary	Measurements and correlation between the levels of synovial fluid IL-1b at three different post-operative points.		1 year