NCT01037738

Brief 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 \[significant differences and narrow confidence intervals\])

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
62

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started May 2006

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2006

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2008

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2009

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

December 3, 2009

Completed
20 days until next milestone

First Posted

Study publicly available on registry

December 23, 2009

Completed
Last Updated

December 23, 2009

Status Verified

January 1, 2009

Enrollment Period

2.3 years

First QC Date

December 3, 2009

Last Update Submit

December 22, 2009

Conditions

Keywords

ACL reconstructionautologous conditioned serumOrthokineosteoarthritisinterleukin receptor antagonistgrowth factorsWOMACIKDC

Outcome Measures

Primary Outcomes (1)

  • Bone tunnel width - CT scans. Clinical efficacy - patient administered outcome instruments (WOMAC, IKDC 2000).

    1 year

Secondary Outcomes (1)

  • Measurements and correlation between the levels of synovial fluid IL-1b at three different post-operative points.

    1 year

Study Arms (2)

ACS - Orthokin

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

Physiologic solution

Procedure: ACL reconstructive surgery and ACS/ Orthokin application

Interventions

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

ACS - OrthokinPlacebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Medical School, University of Zagreb

Zagreb, 10000, Croatia

Location

Related 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.

    BACKGROUND

MeSH Terms

Conditions

Joint InstabilityOsteoarthritis

Condition Hierarchy (Ancestors)

Joint DiseasesMusculoskeletal DiseasesArthritisRheumatic Diseases

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

December 3, 2009

First Posted

December 23, 2009

Study Start

May 1, 2006

Primary Completion

August 1, 2008

Study Completion

January 1, 2009

Last Updated

December 23, 2009

Record last verified: 2009-01

Locations