Clinical trial NCT01133145: Allogeneic Vascularized Knee Transplantation
Official title: Allogenic Vascularized Knee and Femur Transplantation Clinical Evaluation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Osteitis
Limb Salvage
Joint Deformities, Acquired
Skin Transplantation
Bone Transplantation
Keywords: composite tissue allotransplantation
hand transplantation
knee transplantation
face transplantation
Lead sponsor: University of Jena
Sponsor class: OTHER
First posted: 2010-05-28
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: High energy trauma often results in severe soft tissue, bone and joint injury. Today, many methods and techniques exist to treat theses severely injured extremities. Surgical techniques include open reduction and internal fixation (ORIF), e.g. with screws and plates, soft tissue reconstruction by local or free flaps and joint reconstruction by arthroplasty, e.g. total knee arthroplasty. In few, very severe cases, those methods are not sufficient to restore function and amputation is the only option left.

In 1908 the German surgeon Erich Lexer had the idea to transplant a joint. Due to the medical situation at his time the attempts failed.

But the idea survived and was processed over the time. Transplant surgery and medicine developed, immunosuppressive drugs were established and animal models proved that bone and joint transplantation is technically feasible.

In 1998 the first successful hand and in 2005 the first partial face transplantation was carried out. In 1996 we started our clinical femur and knee joint transplantation project.

Detailed description: Sterile osseous defects of the knee joint are temporarily stabilised with a hinge arthroplasty or an intramedullary nail in the case of a long femoral defect.

Assisted passive motion and isometric exercises are possible and necessary to avoid contractions and muscular atrophy during waiting time. Informed consent has to be obtained.

The knee joint is harvested in accordance with standard organ procurement guidelines used in multi-organ donation (MOD). Authorization for knee donation must be obtained from the donor's families. MODs older than 45 years or those who had an accident involving the same leg are excluded. For additional safety reasons, MODs who had received blood substitutes or fresh-frozen plasma are excluded as well.

Harvesting of the knee joint includes perfusion of the External Iliac Artery with 4 L University of Wisconsin (UW) solution at 4°C, dissection of the femoral artery and vein distally to the proximal level of the adductor canal, transsection of the muscles and osteotomy of the femur, tibia and fibula.

To restore normal appearance of the donor leg a polyethylene spacer is inserted into the bone defect and the skin closed.

The graft then is stored in sterile conditions in three layers of plastic bags at 4° C in UW-solution.

Allograft preparation involves dissection from the surrounding soft tissue with the quadriceps tendon and the articular capsule intact, vessels perfusing the muscles ligated and vessels to the bone preserved.

The graft arterial pedicle is perfused with methylene blue to confirm adequate perfusion for transplantation.

The surgical procedure commences with removal of the spacer or nail. The graft is inserted and fixed by an anterograde femoral and a retrograde tibial interlocking compression nail.

The grafts vessels are anastomosed to the recipient's superficial femoral artery and vein using the end-to-side technique. Reperfusion commences immediately while the ligaments and tendons (Quadriceps Tendon, Iliotibial Tract, Gastrocnemius, Hamstrings) were reconstructed.

Immunosuppression is started immediately after reperfusion of the graft and consists of Antithymocyte Globulin (ATG), 4mg / kg bw i.v. as an induction, FK 506 (Tacrolimus; 10mg p.o.), Mycophenolate Mofetil (MMF; 2g p. o.)and Methylprednisolone, 250mg i.v. for the first 3 days. Oral Double-Drug maintenance therapy is continued with MMF (2g p.o.) and FK 506 (Tacrolimus) with a serum level between 8 and 10 µg/ml from the beginning of the third week.

Eligibility criteria: Inclusion Criteria:

* severly injured knee joint with the combination of: massive bone defect plus articulating cartilage defect plus insufficient extensor mechanism (injury of patella, patella ligament or quadriceps tendon)

Exclusion Criteria:

* active osteomyelitis
* history of malignoma
* contraindications for immunosuppressive medication

Primary outcomes:
measure: survival of graft
timeFrame: 2 years after transplantation
Secondary outcomes:
Other outcomes:
Locations:
city: Jena
country: Germany
facility: Klinik für Unfall-, Hand- und Wiederherstellungschirurgie, Universitätsklinikum Jena
Study officials:
affiliation: Clinic of Trauma-, Hand, and Reconstructive Surgery, University of jena
name: Gunther O Hofmann, Prof. Dr.
role: STUDY_DIRECTOR
References:
citation: Hofmann GO, Kirschner MH, Wagner FD, Brauns L, Gonschorek O, Buhren V. Allogeneic vascularized transplantation of human femoral diaphyses and total knee joints--first clinical experiences. Transplant Proc. 1998 Sep;30(6):2754-61. doi: 10.1016/s0041-1345(98)00803-3.
citation: Hofmann GO, Kirschner MH. Clinical experience in allogeneic vascularized bone and joint allografting. Microsurgery. 2000;20(8):375-83. doi: 10.1002/1098-2752(2000)20:83.0.co;2-0.
citation: Kirschner MH, Brauns L, Gonschorek O, Buhren V, Hofmann GO. Vascularised knee joint transplantation in man: the first two years experience. Eur J Surg. 2000 Apr;166(4):320-7. doi: 10.1080/110241500750009186.
citation: Hofmann GO, Kirschner MH, Brauns L, Wagner FD, Land W, Buhren V. Vascularized knee joint transplantation in man: a report on the first cases. Transpl Int. 1998;11 Suppl 1:S487-90. doi: 10.1007/s001470050525.