Foreign-Body ReactionPhase 1/2IMPACTNCT02037204
IMPACT: Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee.
A Phase 1/2 study testing Cartilage repair surgery in people with Foreign-Body Reaction and Inflammation, run by UMC Utrecht at 1 site in Netherlands.
Trial summary
Articular cartilage defects in the knee have a poor intrinsic healing capacity and may lead to functional disability and osteoarthritis. Cartilage cell therapy using autologous chondrocyte implantation (ACI) has been established as the first advanced treatment therapy medicinal product. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Foreign-Body Reaction, Inflammation, Effusion (L) Knee
- What is being tested?
- Cartilage repair surgery
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2013to Apr 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age >18 and <45 years old
- Symptomatic isolated full-thickness articular cartilage lesion on the femoral condyle or trochlea.
- Size 2 - 8 cm2
- Intact anterior cruciate ligament
Who cannot join
- (History of) osteoarthritis, defined as Kellgren-Lawrence grade >3 as determined from appropriate X-ray.
- Concomitant inflammatory disease that affects the joint (rheumatoid arthritis, metabolic bone disease, psoriasis, gout, symptomatic chondrocalcinosis)
- (History of) Septic arthritis.
- Malalignment requiring an osteotomy.
- (History of) total menisectomy in the target knee joint.
- Any surgery in the knee joint 6 months prior to study inclusion.
- Risk groups for MRI scanning due to the magnetic field like patients with pacemakers, nerve stimulators, metal particles, stents, clips or implants, (possible) pregnancy or breast feeding.
- Patients with severe anxiety for MRI scans and/or needles
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Instant MSC Product Accompanying Autologous Chondron Transplantation (IMPACT): Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee.
Articular cartilage defects in the knee have a poor intrinsic healing capacity and may lead to functional disability and osteoarthritis. Cartilage cell therapy using autologous chondrocyte implantation (ACI) has been established as the first advanced treatment therapy medicinal product. Although this technique has achieved good mid-term results, it is a costly and extensive two-stage procedure which is limited by the number of chondrocytes obtained by biopsy and the dedifferentiation resulting from the expansion phase. Therefore, there is a need for improvement. A new cartilage repair technique should aim at decreasing surgical trauma, lowering complexity, improving logistics and cost-effectiveness while retaining or improving clinical outcome. Direct contact between mesenchymal stromal cells (MSCs) and dedifferentiated articular chondrocytes in vitro showed improvement of the chondrogenic phenotype of dedifferentiated articular chondrocytes. In addition, preserving the pericellular matrix of chondrocytes improves cartilage formation. These chondrons (chondrocytes with their pericellular matrix) have shown improved cartilage formation when combined with allogeneic MSCs in extensive preclinical studies. The cells are mixed with fibrin cell carrier and applied to the cartilage lesion within one surgical procedure. This will reduce patient morbidity and improve patient care through immediate transplantation of a potent cell-based cartilage product. This is a phase I/II prospective monocenter study to evaluate the safety and feasibility of the IMPACT for treatment of focal articular cartilage lesions of the knee.
- Being tested
- Cartilage repair surgery
- Keywords
- IMPACT, Chondrons, Mesenchymal stem cells, Allogeneic MSCs, single-stage, Cartilage repair, Safety, Efficacy
- Medical subject headings
- Foreign-Body Reaction, Inflammation, Tooth, Impacted
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cartilage repair surgeryOther
Also called Single-stage, Cartilage repair, IMPACT
Single-stage surgery, After debridement, the cartilage defect is filled with the fibrin glue carrier containing autologous chondrons and allogeneic MSCs
| Study group | Role | What they receive |
|---|---|---|
| Cartilage repair surgery | Experimental | Single-stage cartilage repair surgery using autologous chondrons (10-20%) and allogeneic MSCs (80-90%) in a fibrin glue carrier with a dosage of two million cells/ cm2 applied once during a surgical procedure. Receives: Other: Cartilage repair surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: Adverse Events
Adverse events rate
Measured: 18 months
Secondary outcomes (1)
Clinical Improvement, Knee Injury and Osteoarthritis Outcome Score
Clinical improvement as measured by patient reported outcome scores. The questionnaire has been developed to evaluate the symptoms and limitations for patients with osteoarthritis. The outcome of the KOOS-scale varies from 0-100, where 0 indicates the greatest possible problems and is the worst outcome and 100 indicates no problems.
Measured: 3 and 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2014 (estimated)
- Study startMar 2013
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Foreign-Body ReactionStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- First in man surgery: autologous chondrons are mixed with allogeneic MSCs and implanted in a fibrin glue carrier in a one-stage surgical procedure.
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, D.B.F. Saris, UMC Utrecht
- Investigators
- Tommy S. de Windt, MD, Study director, UMC UtrechtDaniel B.F. Saris, MD, PhD, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02037204
- Sponsor's protocol ID
- IMPACT
- Acronym
- IMPACT
- Status last verified
- Jun 2018
- First submitted
- 13 Jan 2014
- Last updated
- 2 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Bekkers JE, Creemers LB, Tsuchida AI, van Rijen MH, Custers RJ, Dhert WJ, Saris DB. One-stage focal cartilage defect treatment with bone marrow mononuclear cells and chondrocytes leads to better macroscopic cartilage regeneration compared to microfracture in goats. Osteoarthritis Cartilage. 2013 Jul;21(7):950-6. doi: 10.1016/j.joca.2013.03.015. Epub 2013 Apr 9.
PubMed 23583464Bekkers JE, Tsuchida AI, van Rijen MH, Vonk LA, Dhert WJ, Creemers LB, Saris DB. Single-stage cell-based cartilage regeneration using a combination of chondrons and mesenchymal stromal cells: comparison with microfracture. Am J Sports Med. 2013 Sep;41(9):2158-66. doi: 10.1177/0363546513494181. Epub 2013 Jul 5.
PubMed 23831891Vonk LA, Doulabi BZ, Huang C, Helder MN, Everts V, Bank RA. Preservation of the chondrocyte's pericellular matrix improves cell-induced cartilage formation. J Cell Biochem. 2010 May;110(1):260-71. doi: 10.1002/jcb.22533.
PubMed 20213765
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Instant MSC Product Accompanying Autologous Chondron Transplantation (IMPACT): Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee.
- ClinicalTrials.gov ID
- NCT02037204
- Acronym / sponsor ID
- IMPACT / IMPACT
- Keywords
- IMPACT, Chondrons, Mesenchymal stem cells, Allogeneic MSCs, single-stage, Cartilage repair, Safety, Efficacy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Study start
- Mar 2013
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 15 Jan 2014 (estimated)
- Results
- Posted 2 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Articular cartilage defects in the knee have a poor intrinsic healing capacity and may lead to functional disability and osteoarthritis. Cartilage cell therapy using autologous chondrocyte implantation (ACI) has been established as the first advanced treatment therapy medicinal product. Although this technique has achieved good mid-term results, it is a costly and extensive two-stage procedure which is limited by the number of chondrocytes obtained by biopsy and the dedifferentiation resulting from the expansion phase. Therefore, there is a need for improvement. A new cartilage repair technique should aim at decreasing surgical trauma, lowering complexity, improving logistics and cost-effectiveness while retaining or improving clinical outcome. Direct contact between mesenchymal stromal cells (MSCs) and dedifferentiated articular chondrocytes in vitro showed improvement of the chondrogenic phenotype of dedifferentiated articular chondrocytes. In addition, preserving the pericellular matrix of chondrocytes improves cartilage formation. These chondrons (chondrocytes with their pericellular matrix) have shown improved cartilage formation when combined with allogeneic MSCs in extensive preclinical studies. The cells are mixed with fibrin cell carrier and applied to the cartilage lesion within one surgical procedure. This will reduce patient morbidity and improve patient care through immediate transplantation of a potent cell-based cartilage product. This is a phase I/II prospective monocenter study to evaluate the safety and feasibility of the IMPACT for treatment of focal articular cartilage lesions of the knee.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- First in man surgery: autologous chondrons are mixed with allogeneic MSCs and implanted in a fibrin glue carrier in a one-stage surgical procedure.
| Arm | Type | Receives |
|---|---|---|
| Cartilage repair surgery | Experimental | Other: Cartilage repair surgerySingle-stage cartilage repair surgery using autologous chondrons (10-20%) and allogeneic MSCs (80-90%) in a fibrin glue carrier with a dosage of two million cells/ cm2 applied once during a surgical procedure. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Age >18 and <45 years old
- Symptomatic isolated full-thickness articular cartilage lesion on the femoral condyle or trochlea.
- Size 2 - 8 cm2
- Intact anterior cruciate ligament
Key exclusion criteria (8 listed)
- (History of) osteoarthritis, defined as Kellgren-Lawrence grade >3 as determined from appropriate X-ray.
- Concomitant inflammatory disease that affects the joint (rheumatoid arthritis, metabolic bone disease, psoriasis, gout, symptomatic chondrocalcinosis)
- (History of) Septic arthritis.
- Malalignment requiring an osteotomy.
- (History of) total menisectomy in the target knee joint.
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 |
|---|---|---|
| Cartilage repair surgeryAlso: Single-stage, Cartilage repair, IMPACTSingle-stage surgery, After debridement, the cartilage defect is filled with the fibrin glue carrier containing autologous chondrons and allogeneic MSCs | Other | Cartilage repair surgery |
Primary outcome
Safety: Adverse Events
Time frame: 18 months
Adverse events rate
1 secondary outcome
Clinical Improvement, Knee Injury and Osteoarthritis Outcome Score
Time frame: 3 and 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23583464Bekkers JE, Creemers LB, Tsuchida AI, van Rijen MH, Custers RJ, Dhert WJ, Saris DB. One-stage focal cartilage defect treatment with bone marrow mononuclear cells and chondrocytes leads to better macroscopic cartilage regeneration compared to microfracture in goats. Osteoarthritis Cartilage. 2013 Jul;21(7):950-6. doi: 10.1016/j.joca.2013.03.015. Epub 2013 Apr 9.
- Background: PubMed 23831891Bekkers JE, Tsuchida AI, van Rijen MH, Vonk LA, Dhert WJ, Creemers LB, Saris DB. Single-stage cell-based cartilage regeneration using a combination of chondrons and mesenchymal stromal cells: comparison with microfracture. Am J Sports Med. 2013 Sep;41(9):2158-66. doi: 10.1177/0363546513494181. Epub 2013 Jul 5.
- Background: PubMed 20213765Vonk LA, Doulabi BZ, Huang C, Helder MN, Everts V, Bank RA. Preservation of the chondrocyte's pericellular matrix improves cell-induced cartilage formation. J Cell Biochem. 2010 May;110(1):260-71. doi: 10.1002/jcb.22533.
- Trials Register of the European UnionLink provided by the sponsor.
- IMPACT animationLink provided by the sponsor.
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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.
Tommy S. de Windt, MD study director
UMC Utrecht
Daniel B.F. Saris, MD, PhD principal investigator
UMC Utrecht
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cartilage repair surgery in people with Foreign-Body Reaction and Inflammation, run by UMC Utrecht at 1 site in Netherlands.
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 4 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 2 Jan 2019. 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 Netherlands. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Safety: Adverse Events (time frame: 18 months). 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 NCT02037204, which also lists 3 linked publications.
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 2 Jan 2019.