Joint InstabilityPhase 1NCT01037738
Study of Autologous Conditioned Serum After Anterior Cruciate Ligament Reconstructive Surgery
A Phase 1 study testing ACL reconstructive surgery and ACS/ Orthokin application in people with Joint Instability, run by University of Zagreb at 1 site in Croatia.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Joint Instability
- What is being tested?
- ACL reconstructive surgery and ACS/ Orthokin application
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteCroatia
- Study dates
- May 2006to Jan 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
Abstract
Background
Read more
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])
- Conditions
- Joint Instability
- Being tested
- ACL reconstructive surgery and ACS/ Orthokin application
- Keywords
- ACL reconstruction, autologous conditioned serum, Orthokine, osteoarthritis, interleukin receptor antagonist, growth factors, WOMAC, IKDC
- Medical subject headings
- Joint Instability, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACL reconstructive surgery and ACS/ Orthokin applicationProcedure or surgery
ACL reconstructive surgery and ACS/ Orthokin or Placebo intraarticular application on Day 0,1,6 and 10 postoperatively, regarding the Arm
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: ACL reconstructive surgery and ACS/ Orthokin application |
| Placebo | Placebo comparator | Physiologic solution Receives: Procedure: ACL reconstructive surgery and ACS/ Orthokin application |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bone tunnel width - CT scans. Clinical efficacy - patient administered outcome instruments (WOMAC, IKDC 2000).
Measured: 1 year
Secondary outcomes (1)
Measurements and correlation between the levels of synovial fluid IL-1b at three different post-operative points.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2009 (estimated)
- Study startMay 2006
- Primary completionAug 2008
- Study completionJan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Joint InstabilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zagreb
- Sponsor type
- University, hospital or other
- Collaborators
- Croatian Institute of Health Insurance
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01037738
- Sponsor's protocol ID
- REC LCA 2B
- Status last verified
- Jan 2009
- First submitted
- 3 Dec 2009
- Last updated
- 23 Dec 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01037738
- Acronym / sponsor ID
- REC LCA 2B
- Conditions
- Joint Instability
- Keywords
- ACL reconstruction, autologous conditioned serum, Orthokine, osteoarthritis, interleukin receptor antagonist, growth factors, WOMAC, IKDC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- University of ZagrebUniversity, hospital or other
- Collaborators
- Croatian Institute of Health Insurance
- Study start
- May 2006
- Primary completion
- Aug 2008 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 23 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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])
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ACS - Orthokin | Active comparator | Procedure: ACL reconstructive surgery and ACS/ Orthokin applicationAutologous 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. |
| Placebo | Placebo comparator | Procedure: ACL reconstructive surgery and ACS/ Orthokin applicationPhysiologic solution |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ACL reconstructive surgery and ACS/ Orthokin applicationACL reconstructive surgery and ACS/ Orthokin or Placebo intraarticular application on Day 0,1,6 and 10 postoperatively, regarding the Arm | Procedure or surgery | ACS - Orthokin, Placebo |
Primary outcome
Bone tunnel width - CT scans. Clinical efficacy - patient administered outcome instruments (WOMAC, IKDC 2000).
Time frame: 1 year
1 secondary outcome
Measurements and correlation between the levels of synovial fluid IL-1b at three different post-operative points.
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2009.
- BackgroundReferences 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ACL reconstructive surgery and ACS/ Orthokin application in people with Joint Instability, run by University of Zagreb at 1 site in Croatia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Dec 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Croatia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bone tunnel width - CT scans. Clinical efficacy - patient administered outcome instruments (WOMAC, IKDC 2000). (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01037738, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2009.