IMPACT: Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee. (IMPACT)
Primary Purpose
Foreign-Body Reaction, Inflammation, Effusion (L) Knee
Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Cartilage repair surgery
Sponsored by
About this trial
This is an interventional treatment trial for Foreign-Body Reaction focused on measuring IMPACT, Chondrons, Mesenchymal stem cells, Allogeneic MSCs, single-stage, Cartilage repair, Safety, Efficacy
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- (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
Sites / Locations
- University Medical Center Utrecht
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cartilage repair surgery
Arm Description
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.
Outcomes
Primary Outcome Measures
Safety: Adverse Events
Adverse events rate
Secondary Outcome Measures
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02037204
Brief Title
IMPACT: Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee.
Acronym
IMPACT
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.
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
April 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
UMC Utrecht
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Foreign-Body Reaction, Inflammation, Effusion (L) Knee, Knee Pain Swelling
Keywords
IMPACT, Chondrons, Mesenchymal stem cells, Allogeneic MSCs, single-stage, Cartilage repair, Safety, Efficacy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cartilage repair surgery
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Cartilage repair surgery
Other Intervention Name(s)
Single-stage, Cartilage repair, IMPACT
Intervention Description
Single-stage surgery, After debridement, the cartilage defect is filled with the fibrin glue carrier containing autologous chondrons and allogeneic MSCs
Primary Outcome Measure Information:
Title
Safety: Adverse Events
Description
Adverse events rate
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Clinical Improvement, Knee Injury and Osteoarthritis Outcome Score
Description
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.
Time Frame
3 and 18 months
Other Pre-specified Outcome Measures:
Title
Structural Repair
Description
To examine parameters of structural repair at one year after treatment using MRI and a second-look arthroscopy.
Time Frame
12 months
Title
Health Care Use and Costs
Description
To assess the healthcare use and costs related to the procedure as well as the health-related work leave during the study period.
Time Frame
18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
(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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tommy S. de Windt, MD
Organizational Affiliation
UMC Utrecht
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Daniel B.F. Saris, MD, PhD
Organizational Affiliation
UMC Utrecht
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Medical Center Utrecht
City
Utrecht
ZIP/Postal Code
3508GA
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
23583464
Citation
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.
Results Reference
background
PubMed Identifier
23831891
Citation
Bekkers 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.
Results Reference
background
PubMed Identifier
20213765
Citation
Vonk 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.
Results Reference
background
Links:
URL
https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-001570-29/NL
Description
Trials Register of the European Union
URL
https://www.youtube.com/watch?v=S3rIBjA03AA
Description
IMPACT animation
Learn more about this trial
IMPACT: Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee.
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