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

NCT02037204 | Completed Phase 1 Results DMC

• 1 other identifier: IMPACT
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Safety: Adverse Events

  Adverse events rate

  18 months

Secondary Outcomes (1)

• Clinical Improvement, Knee Injury and Osteoarthritis Outcome Score

  3 and 18 months

Other Outcomes (2)

• Structural Repair

  12 months

• Health Care Use and Costs

  18 months

Study Arms (1)

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.

Other: Cartilage repair surgery

Interventions

Cartilage repair surgery OTHER

Single-stage surgery, After debridement, the cartilage defect is filled with the fibrin glue carrier containing autologous chondrons and allogeneic MSCs

Also known as: Single-stage, Cartilage repair, IMPACT

Cartilage repair surgery

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• (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.
• 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

Sponsors & Collaborators

• UMC Utrecht: lead

Study Sites (1)

University Medical Center Utrecht

Utrecht, 3508GA, Netherlands

Location

Related Publications (3)

• 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.

  PMID: 23583464 BACKGROUND

• 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.

  PMID: 23831891 BACKGROUND

• 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.

  PMID: 20213765 BACKGROUND

Related Links

• Trials Register of the European Union
• IMPACT animation

MeSH Terms

Conditions

Foreign-Body Reaction; Inflammation; Tooth, Impacted

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Foreign Bodies; Wounds and Injuries; Tooth Diseases; Stomatognathic Diseases

Results Point of Contact

• Title: Prof. Daniel Saris
• Organization: UMC Utrecht

d.saris@umcutrecht.nl

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Study Officials

• Tommy S. de Windt, MD

  UMC Utrecht

  STUDY DIRECTOR

• Daniel B.F. Saris, MD, PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Orthopaedic surgeon

Model Details: First in man surgery: autologous chondrons are mixed with allogeneic MSCs and implanted in a fibrin glue carrier in a one-stage surgical procedure.

Study Record Dates

• First Submitted: January 13, 2014
• First Posted: January 15, 2014
• Study Start: March 1, 2013
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: January 2, 2019
• Results First Posted: January 2, 2019

Record last verified: 2018-06

Locations

NL (1)