IMPACT: Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee. (IMPACT)

• ClinicalTrials.gov Identifier: NCT02037204
• Recruitment Status: Completed
• First Posted: January 15, 2014
• Results First Posted: January 1, 2019
• Last Update Posted: January 1, 2019
• Sponsor: UMC Utrecht
• Information provided by (Responsible Party): D.B.F. Saris, UMC Utrecht

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.

Condition or disease	Intervention/treatment	Phase
Foreign-Body Reaction; Inflammation; Effusion (L) Knee; Knee Pain Swelling	Other: Cartilage repair surgery	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 35 participants
• Intervention Model: Single Group Assignment
• 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.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: March 2013
• Actual Primary Completion Date: April 2016
• Actual Study Completion Date: April 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cartilage repair surgery; 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.	Other: Cartilage repair surgery; Single-stage surgery, After debridement, the cartilage defect is filled with the fibrin glue carrier containing autologous chondrons and allogeneic MSCs; Other Names: Single-stage; Cartilage repair; IMPACT

Outcome Measures

Primary Outcome Measures :

1. Safety: Adverse Events [ Time Frame: 18 months ]
   Adverse events rate

Secondary Outcome Measures :

1. Clinical Improvement, Knee Injury and Osteoarthritis Outcome Score [ Time Frame: 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 Outcome Measures:

1. Structural Repair [ Time Frame: 12 months ]
   To examine parameters of structural repair at one year after treatment using MRI and a second-look arthroscopy.
2. Health Care Use and Costs [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Netherlands

University Medical Center Utrecht

Utrecht, Netherlands, 3508GA

Sponsors and Collaborators

UMC Utrecht

Investigators

• Study Director: Tommy S. de Windt, MD; UMC Utrecht
• Principal Investigator: Daniel B.F. Saris, MD, PhD; UMC Utrecht

More Information

Additional Information:

Trials Register of the European Union  IMPACT animation 

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.

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.

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.

• Responsible Party: D.B.F. Saris, MD, PhD, Orthopaedic surgeon, UMC Utrecht
• ClinicalTrials.gov Identifier: NCT02037204 History of Changes
• Other Study ID Numbers: IMPACT
• First Posted: January 15, 2014
• Results First Posted: January 1, 2019
• Last Update Posted: January 1, 2019
• Last Verified: June 2018

Keywords provided by D.B.F. Saris, UMC Utrecht:

IMPACT; Chondrons; Mesenchymal stem cells; Allogeneic MSCs; single-stage; Cartilage repair; Safety; Efficacy

Additional relevant MeSH terms:

Inflammation; Foreign-Body Reaction; Foreign Bodies; Pathologic Processes; Wounds and Injuries