Tissue Engineered Nasal Cartilage for Regeneration of Articular Cartilage - Full Text View

Purpose

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 of the knee after a traumatic injury.

Condition	Intervention	Phase
Cartilage Lesion Lesion of Articular Cartilage of the Knee	Biological: Tissue engineered cartilage graft	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Tissue Engineered Nasal Cartilage for Regeneration of Articular Cartilage in the Knee After Traumatic Injury - a Phase I Clinical Trial-

Resource links provided by NLM:

MedlinePlus related topics: Injuries Wounds

U.S. FDA Resources

Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:

1-Safety for the patient [ Time Frame: until 24 months ] [ Designated as safety issue: Yes ]
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.
2- Stability of the graft [ Time Frame: until 24 months ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Subjective pain relief [ Time Frame: until 24 months ] [ Designated as safety issue: No ]
Subjective relief of pain for the patient will be assessed using the 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.

Estimated Enrollment:	10
Study Start Date:	May 2012
Estimated Study Completion Date:	August 2016
Estimated Primary Completion Date:	August 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Implantation of cartilage graft	Biological: Tissue engineered cartilage graft Autologous nasal chondrocytes expanded in vitro and cultured in a collagen type I//III scaffold

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 10 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 an isolated full-thickness cartilage defect from 2 cm2 to 8 cm2 due to traumatic injury on the femoral condyle of the knee.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Size of the defect on the femoral cartilage:symptomatic isolated lesion grade III-IV from 2 cm2 to 8 cm2 at the femoral condyle
Other:
Age: 18-55 years
Written informed consent by the patient

Exclusion Criteria:

Defect:
- Lesions smaller than 2cm2 or greater than 8cm2
- Lesions other than on the femoral condyle
- 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
- Patients with acute infection for EBV (Epstein bar virus), CMV
- 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01605201

Locations

Switzerland
University Hospital Basel	Recruiting
Basel, Switzerland, 4031
Contact: Marcel Jakob, Prof.Dr. +41 61 328 72 40 JakobM@uhbs.ch
Contact: Markus Arnold, PD Dr. +41 61 436 36 76 Markus.Arnold@ksbh.ch
Principal Investigator: Marcel Jakob, Prof.Dr.

Sponsors and Collaborators

University Hospital, Basel, Switzerland

Deutsche Arthrose-Hilfe

Investigators

Principal Investigator:

Marcel Jakob, Prof. Dr.

University Hospital, Basel, Switzerland

More Information

No publications provided

Responsible Party:	University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:	NCT01605201 History of Changes
Other Study ID Numbers:	92/11, TpP-I-2012-001
Study First Received:	May 22, 2012
Last Updated:	May 24, 2012
Health Authority:	Switzerland: Swissmedic

Keywords provided by University Hospital, Basel, Switzerland:

Chondral lesions in the knee after traumatic injury

Additional relevant MeSH terms:

Wounds and Injuries

ClinicalTrials.gov processed this record on May 21, 2013

Tissue Engineered Nasal Cartilage for Regeneration of Articular Cartilage (Nose2Knee)