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

Tracking Information
First Submitted Date ICMJE	May 22, 2012
First Posted Date ICMJE	May 24, 2012
Last Update Posted Date	August 27, 2018
Actual Study Start Date ICMJE	August 29, 2012
Actual Primary Completion Date	August 15, 2018 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 23, 2012)	1-Safety for the patient [ Time Frame: until 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.; 2- Stability of the graft [ Time Frame: until 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.
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01605201 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: June 21, 2013)	Subjective pain relief [ Time Frame: until 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.
Original Secondary Outcome Measures ICMJE; (submitted: May 23, 2012)	Subjective pain relief [ Time Frame: until 24 months ]; 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.
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Tissue Engineered Nasal Cartilage for Regeneration of Articular Cartilage
Official Title ICMJE	Tissue Engineered Nasal Cartilage for Regeneration of Articular Cartilage in the Knee After Traumatic Injury - a Phase I Clinical Trial-
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.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Cartilage Lesion; Degenerative Lesion of Articular Cartilage of Knee
Intervention ICMJE	Biological: Tissue engineered cartilage graft; Autologous nasal chondrocytes expanded in vitro and cultured in a collagen type I//III scaffold
Study Arms	Experimental: Implantation of cartilage graft; Intervention: Biological: Tissue engineered cartilage graft
Publications *	Mumme M, Barbero A, Miot S, Wixmerten A, Feliciano S, Wolf F, Asnaghi AM, Baumhoer D, Bieri O, Kretzschmar M, Pagenstert G, Haug M, Schaefer DJ, Martin I, Jakob M. Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial. Lancet. 2016 Oct 22;388(10055):1985-1994. doi: 10.1016/S0140-6736(16)31658-0.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: January 12, 2017)	18
Original Estimated Enrollment ICMJE; (submitted: May 23, 2012)	10
Actual Study Completion Date	August 15, 2018
Actual Primary Completion Date	August 15, 2018 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 55 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Switzerland
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01605201
Other Study ID Numbers ICMJE	92/11; TpP-I-2012-001 ( Other Identifier: Swissmedic )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	University Hospital, Basel, Switzerland
Study Sponsor ICMJE	University Hospital, Basel, Switzerland
Collaborators ICMJE	Deutsche Arthrose-Hilfe
Investigators ICMJE	Principal Investigator: Marcel Jakob, Prof. Dr. University Hospital, Basel, Switzerland
PRS Account	University Hospital, Basel, Switzerland
Verification Date	August 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP