Allogeneic Vascularized Knee Transplantation

Limb Salvage Clinical Trial

— kneeTx  

Official title:

Allogenic Vascularized Knee and Femur Transplantation Clinical Evaluation

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT01133145
• Other study ID #: knee Tx
• Status: Enrolling by invitation
• Phase: N/A
• First received: May 27, 2010
• Last updated: May 27, 2010
• Est. completion date: June 2012

Study information

• Verified date: May 2010
• Source: University of Jena
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 6
• Est. completion date: June 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bone Transplantation
• Joint Deformities, Acquired
• Limb Salvage
• Osteitis
• Skin Transplantation

Intervention

Procedure:
• knee joint transplantation
transplantation of a kne joint from a multi organ donor to a recipient with a severly injured knee joint

Locations

Country	Name	City	State
Germany	Klinik für Unfall-, Hand- und Wiederherstellungschirurgie, Universitätsklinikum Jena	Jena

Sponsors (1)

Lead Sponsor	Collaborator
University of Jena

Country where clinical trial is conducted

Germany, 

References & Publications (4)

Hofmann GO, Kirschner MH, Brauns L, Wagner FD, Land W, Bühren V. Vascularized knee joint transplantation in man: a report on the first cases. Transpl Int. 1998;11 Suppl 1:S487-90. — View Citation

Hofmann GO, Kirschner MH, Wagner FD, Brauns L, Gonschorek O, Bühren V. Allogeneic vascularized transplantation of human femoral diaphyses and total knee joints--first clinical experiences. Transplant Proc. 1998 Sep;30(6):2754-61. — View Citation

Hofmann GO, Kirschner MH. Clinical experience in allogeneic vascularized bone and joint allografting. Microsurgery. 2000;20(8):375-83. — View Citation

Kirschner MH, Brauns L, Gonschorek O, Bühren V, Hofmann GO. Vascularised knee joint transplantation in man: the first two years experience. Eur J Surg. 2000 Apr;166(4):320-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	survival of graft	Clinical examination of graft, x-rays	2 years after transplantation	Yes

External Links

•   University of Jena, Medicine