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Tissue Engineered Nasal Cartilage for Regeneration of Articular Cartilage

Phase 1
Completed
Conditions
Cartilage Lesion
Degenerative Lesion of Articular Cartilage of Knee
Interventions
Biological: Tissue engineered cartilage graft
Registration Number
NCT01605201
Lead Sponsor
University Hospital, Basel, Switzerland
Brief Summary

The purpose of this study is to investigate the safety and feasibility of implanting an engineered cartilage graft obtained by culturing expanded autologous nasal chondrocytes within a collagen type I/III membrane into the cartilage defect on the femoral condyle and/or trochlea of the knee after a traumatic injury.

Detailed Description

Articular cartilage injuries are a prime target for regenerative techniques, since spontaneous healing is poor and untreated defects predispose to osteoarthritis. Common current strategies such as arthroscopic debridement, microfracture, autologous osteochondral grafting, use of allografts and autologous chondrocytes implantation (ACI) still have drawbacks such as long and complex rehabilitation times, technically challenging operation techniques, defect-size limitations, donor-site morbidity, limited graft material and high costs. Furthermore many techniques show unsatisfactory long term results due to inferior quality of repair tissue as compared to native cartilage or have yet to prove the cost versus benefit. These drawbacks could be overcome by using a tissue engineered nasal cartilage graft, thereby reducing donor site morbidity without introducing additional risk of complication or technically challenging techniques.

This study is a phase I, prospective, uncontrolled, investigator initiated clinical trial involving 25 patients, with the objective of demonstrating safety and feasibility in the use of engineered nasal cartilage grafts for repair of articular cartilage. The specific surgical target of the trial is the repair of one or two full-thickness cartilage defects from 2 cm2 to 8 cm2 (per lesion, not exceeding a total of 8 cm2 for all lesions) due to traumatic injury on the femoral condyle and/or trochlea of the knee.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
18
Inclusion Criteria
  • Size of the defect on the femoral cartilage:one or two symptomatic lesion(s) grade III-IV from 2 cm2 to 8 cm2 at the femoral condyle and/or trochlea
  • Other:
  • Age: 18-55 years
  • Written informed consent by the patient
Exclusion Criteria
  • Defect:

    • Lesions smaller than 2cm2 or greater than 8cm2
    • Total area of all lesions bigger than 8cm2
    • Lesions other than on the femoral condyle and/or trochlea
    • Any evidence of the following diseases in the target joint: septic arthritis; inflammatory joint disease; gout; recurrent episodes of pseudogout; Paget disease of bone; ochronosis; acromegaly; hemochromatosis;Wilson disease; primary osteochondromatosis; heritable disorders; collagen gene mutations
    • Presence of a clinically relevant cartilage lesion on the patella (second lesion)
    • Patellofemoral cartilage lesion
    • Presence of relevant complex knee injuries affecting bone and/or ligaments
    • Osteochondritis dissecans: recent (within 1 year before baseline); depth of lesion >0.5 cm; subchondral sclerosis
    • Advanced osteoarthritis (as defined by Radiographic Atlas of Osteoarthritis, grade 2-3)
    • Varus or valgus malalignment exceeding 5° (kissing lesions out)
  • Medical history:

    • gravidity (Pregnancy)
    • breast feeding
    • presence of multiple severe allergies (including porcine collagen, streptomycin and penicillin)
    • Osteoarthritis
    • Current diagnosis of osteomyelitis
    • Any clinically significant or symptomatic vascular or neurologic disorder of the lower extremities
    • A blood result showing liver enzymes (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase) of more than 2 times the upper limit of normal or any other result that in the clinical investigator's mind is clinically important
    • C-reactive protein level greater than 10 mg/L
    • Uncontrolled diabetes
    • Renal insufficiency
    • Previous pacemaker implantation
    • Any concomitant painful or disabling disease of the spine, hips, or lower limbs that would interfere with evaluation of the afflicted knee
    • Mosaicplasty (osteochondral autograft transfer system)
    • Microfracture performed less than 1 year before baseline
    • Received hyaluronic acid intra-articular injections into the afflicted knee within the last 6 months of baseline Meniscal transplant (previous/present)
    • Meniscal suture with meniscal arrows ipsilaterally (present or previous if not resorbed)
    • Taking specific osteoarthritis drugs, such as chondroitin sulfate, diacerein, n-glucosamine, piascledine, and capsaicin, within 2 weeks of the baseline visit
    • Corticosteroid therapy by systemic or intra-articular route within the last month of baseline or intramuscular or oral corticosteroids within the last 2 weeks of baseline
    • Chronic use of anticoagulants
    • Patients with human immunodeficiency virus, hepatitis, or syphilis
    • Malignancy
    • Alcohol and drug (medication) abuse
    • Poor general health condition as judged by investigator
    • Body mass index >35 kg/m2
    • Medication:chronic treatment with steroids or growth factors (immunomodulatory drugs)
  • Other:

    • Participation in concurrent clinical trials
    • Participation in a previous clinical trial within 1 year

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Implantation of cartilage graftTissue engineered cartilage graft-
Primary Outcome Measures
NameTimeMethod
2- Stability of the graftuntil 24 months

It will be assessed by Magnetic Resonance Imaging (MRI) technique at 6, 12 and 24 months indicating if the graft is in place and if there are signs of complications. Parameters to be evaluated are: filling of the defect, integration of the border zone to the adjacent cartilage, intactness of the subchondral lamina, intactness of the subchondral bone, and relative signal intensities of the repair tissue compared to the adjacent native cartilage.

1-Safety for the patientuntil 24 months

Safety will be assessed by the incidence of adverse reactions and adverse events. Expected postoperative complications also occurring in the standard procedure are: pain, swelling and hematoma, casually post-anesthetic nausea, vomiting or fever.

Secondary Outcome Measures
NameTimeMethod
Subjective pain reliefuntil 24 months

Subjective relief of pain for the patient will be assessed using the International Cartilage Repair Society (ICRS) Cartilage Injury Evaluation Package which includes the pre- and postsurgical evaluation of general medical conditions, pain, activity level as well as functional and morphological status.

Trial Locations

Locations (1)

University Hospital Basel

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Basel, Switzerland

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