Clinical trial NCT02037204: IMPACT: Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee.
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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Foreign-Body Reaction
Inflammation
Effusion (L) Knee
Knee Pain Swelling
Keywords: IMPACT
Chondrons
Mesenchymal stem cells
Allogeneic MSCs
single-stage
Cartilage repair
Safety
Efficacy
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
First posted: 2014-01-15
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Safety: Adverse Events
timeFrame: 18 months
Secondary outcomes:
measure: Clinical Improvement, Knee Injury and Osteoarthritis Outcome Score
timeFrame: 3 and 18 months
Other outcomes:
measure: Structural Repair
timeFrame: 12 months
measure: Health Care Use and Costs
timeFrame: 18 months
Locations:
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: UMC Utrecht
name: Tommy S. de Windt, MD
role: STUDY_DIRECTOR
affiliation: UMC Utrecht
name: Daniel B.F. Saris, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.