Effusion (L) Knee, Foreign-Body Reaction, Inflammation, Knee Pain Swelling
Conditions
Keywords
IMPACT, Chondrons, Mesenchymal stem cells, Allogeneic MSCs, single-stage, Cartilage repair, Safety, Efficacy
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.
Interventions
OTHERCartilage repair surgery
Single-stage surgery, After debridement, the cartilage defect is filled with the fibrin glue carrier containing autologous chondrons and allogeneic MSCs
Sponsors
UMC Utrecht
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Adverse Events | 18 months | Adverse events rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Improvement, Knee Injury and Osteoarthritis Outcome Score | 3 and 18 months | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Structural Repair | 12 months | To examine parameters of structural repair at one year after treatment using MRI and a second-look arthroscopy. |
| Health Care Use and Costs | 18 months | To assess the healthcare use and costs related to the procedure as well as the health-related work leave during the study period. |
Countries
Netherlands
Participant flow
Recruitment details
Patient recruitment started on February 1st 2013 and was completed in September 2014
Pre-assignment details
Four patients were excluded based on MRI scans showing multiple cartilage defects and/ or osteochondral defects. Inclusion was continued until n = 35 was reached
Participants by arm
| Arm | Count |
|---|---|
| Cartilage Repair Surgery Single-stage cartilage repair surgery using autologous chondrons and allogeneic MSCs in a fibrin glue carrier.
Cartilage repair surgery: Single-stage surgery, After debridement, the cartilage defect is filled with the fibrin glue carrier containing autologous chondrons and allogeneic MSCs | 35 |
| Total | 35 |
Baseline characteristics
| Characteristic | Cartilage Repair Surgery |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants |
| Age, Continuous | 33 years STANDARD_DEVIATION 8 |
| Region of Enrollment Netherlands | 35 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 18 / 35 |
| serious Total, serious adverse events | 0 / 35 |
Outcome results
Primary
Safety: Adverse Events
Adverse events rate
Time frame: 18 months
Population: All patients were monitored for the duration of the studie for inflammation and signs of a foreign body response by an independent physician using standardized clinical measures, pain assessment by numeric rating scale for pain and blood analysis including serum C-reactive protein, erythrocyte sedimentation rate and leukocyte count.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cartilage Repair Surgery | Safety: Adverse Events | 0 participants |
Secondary
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.
Time frame: 3 and 18 months
Population: Differences in clinical outcome between baseline and 3 and 12 months after surgery were tested by a repeated measures analysis of variance (ANOVA).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cartilage Repair Surgery | Clinical Improvement, Knee Injury and Osteoarthritis Outcome Score | KOOS outcome baseline | 57.9 units on a scale | Standard Deviation 16.1 |
| Cartilage Repair Surgery | Clinical Improvement, Knee Injury and Osteoarthritis Outcome Score | KOOS outcome 3 months | 76.6 units on a scale | Standard Deviation 11.1 |
| Cartilage Repair Surgery | Clinical Improvement, Knee Injury and Osteoarthritis Outcome Score | KOOS outcome 18 months | 85.4 units on a scale | Standard Deviation 13.3 |
Comparison: A repeated-measures analysis of variance was used to test for differences in clinical outcome between baseline and 3, and 18 months after surgery.p-value: <0.05ANOVA
Other Pre-specified
Health Care Use and Costs
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
Other Pre-specified
Structural Repair
To examine parameters of structural repair at one year after treatment using MRI and a second-look arthroscopy.
Time frame: 12 months