Clinical trial NCT01206179: Treatment of Non Union of Long Bone Fractures by Autologous Mesenchymal Stem Cell
Official title: Effect of Bone Marrow-derived Mesenchymal Stem Cell Transplantation in Reconstructing Human Bone Defects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Nonunion Fractures
Keywords: nonunion fracture bone formation pain relief
Lead sponsor: Royan Institute
Sponsor class: OTHER_GOV
First posted: 2010-09-21
Enrollment: 6
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Treatment of nonunion, delayed union and malunion fractures of long bones remains problematic. The definition of nonunion is a failure of the fracture to heal in six months in a patient in whom progressive repair had not been observed radiographically between the third and sixth month after the fracture. First of all good surgical techniques are stable immobilization must be obtained and local sepsis excluded. Then stimulation of the callus is required. Numerous techniques have been developed ranging from invasive interventions (including internal fixation with the use of bone graft or bone graft substitutes) to non invasive procedures (ultrasound and pulsed electromagnetic fields).

Recently, autologous cell therapy was presented as an interesting approach. The concept of such therapies is based on the effect of stem cells presented in the bone marrow and able to be transformed in osteoblast cells. The purpose of this study is to find if mesenchymal stem cells can stimulate bone regeneration in nonunion and delayed union fractures to reduce later surgeries required to augment the healing process and to accelerate the time to healing.

Detailed description: Treatment of nonunion, delayed union and malunion fractures of long bones remains problematic. The definition of nonunion is a failure of the fracture to heal in six months in a patient in whom progressive repair had not been observed radiographically between the third and sixth month after the fracture. Nonunion is a serious complication of a fracture, occurring in 2-10% of patients, as it is associated with high economic and health burden. Many cases are subsequently approached by multiple surgical and nonsurgical modalities. Various devices, under the name of "bone growth stimulators" have been used to enhance healing of the fracture. Recent studies, demonstrated the efficacy of mesenchymal stem cells in regeneration of bone and cartilage tissue. In this study percutaneous injection of mesenchymal stem cells to the site of fracture is performed as an outpatient procedure or during an operative exposure to evaluate its efficacy in enhancing bone regeneration. In the case of small size of bone gap, mesenchymal stem cells are injected into the callus of fracture site through an outpatient procedure under the guide of fluoroscopy. If there is a large bone gap, through a surgical management, mesenchymal stem cells seeded on bone matrix are placed at the site of fracture. Patients are followed by X-Ray examination 1,2,6, and 12 months after treatment.

Eligibility criteria: * Inclusion criteria:
* Both genders are eligible
* Nonunion or delayed union diagnosed with X-Ray examination.
* More than 4 cm distance to joint
* Provided written informed consent
* Exclusion criteria:
* Multiple major fracture or untreated major fracture
* Infected fracture
* HIV, hepatitis B or hepatitis C infection at the time of screening
* Pregnant or lactating women
* Diagnosis of cancer
* Active treatment with immunosuppressive drugs or anticoagulant agent
* Known allergic reaction to components of study treatment and/or study injection procedure

Primary outcomes:
measure: Radiological progression of bone fusion
timeFrame: 3 months
Secondary outcomes:
measure: Reduction of pain using VAS
timeFrame: 6 months
measure: Cost analysis based on length of hospital stay
timeFrame: 6 months
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Royan Institute
Study officials:
affiliation: President of Royan Institute
name: Hamid Gourabi, PhD
role: STUDY_CHAIR
affiliation: Sientific Board
name: Mohammad reza Baghban Eslami Nejad, PhD
role: STUDY_DIRECTOR
affiliation: Orthopadic Investigator
name: Mohssen Emadeddin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Head of Regenerative center
name: Nasser Aghdami, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radiologist investigator
name: Ahmad Vosough, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Emadedin M, Labibzadeh N, Fazeli R, Mohseni F, Hosseini SE, Moghadasali R, Mardpour S, Azimian V, Goodarzi A, Ghorbani Liastani M, Mirazimi Bafghi A, Baghaban Eslaminejad M, Aghdami N. Percutaneous Autologous Bone Marrow-Derived Mesenchymal Stromal Cell Implantation Is Safe for Reconstruction of Human Lower Limb Long Bone Atrophic Nonunion. Cell J. 2017 Apr-Jun;19(1):159-165. doi: 10.22074/cellj.2016.4866. Epub 2016 Dec 21.
citation: Labibzadeh N, Emadedin M, Fazeli R, Mohseni F, Hosseini SE, Moghadasali R, Mardpour S, Azimian V, Ghorbani Liastani M, Mirazimi Bafghi A, Baghaban Eslaminejad M, Aghdami N. Mesenchymal Stromal Cells Implantation in Combination with Platelet Lysate Product Is Safe for Reconstruction of Human Long Bone Nonunion. Cell J. 2016 Fall;18(3):302-309. doi: 10.22074/cellj.2016.4557. Epub 2016 Aug 24.