Autologous BM-MSC Transplantation in Combination With Platelet Lysate (PL) for Nonunion Treatment

Use of Autologous Bone Marrow Derived Mesenchymal Stromal Cells in Combination With Platelet Lysate Product for Human Long Bone Nonunion Treatment, A Phase 2-3 Clinical Trial

Nonunion of long bones would occur in almost 10% of fractures and because of its long term and complicated treatment, is known as a therapeutic challenge for both of the surgeons and patients.

Cell therapy is useful in treatment of nonunion and mesenchymal stromal/stem cells are the best candidates for this kind of treatment.

Percutaneous implantation of autologous bone marrow derived mesenchymal stromal/stem cell in combination with PL will be done in 30 patients with tibia nonunion. The other 30 patients as the control group will receive placebo. The patients will be followed at 2weeks, 3months, 6m and 12 months after implantation.

The Spss(v16) software will be used for data analysis.

Study Overview

• Status: Unknown
• Conditions: Bone Fracture
• Intervention / Treatment: Biological: Percutaneous injection; Other: Percutaneous injection

Detailed Description

Long bone nonunion is known as a therapeutic challenge for both the orthopedic surgeons and the society. Current treatment of this disorder is autologous bone graft. This treatment has potential minor and major complications and is considered as a risky treatment. So researches are focused on new treatment approaches for this disease.

Cell therapy is one of these new approaches especially based on mesenchymal stromal cells.

The investigators will evaluate safety and efficacy of percutaneous implantation of autologous BM-MSC (bone marrow -derived mesenchymal stromal cell) in combination with PL (platelet lysate product) in 30 tibia nonunion patients. The other 30 patients will receive placebo. These patients will be followed up and data will be analyzed with spss(v16).

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Recruiting
    • Royan Institute
    • Contact: Leila Arab, MD; Phone Number: 414 (+98)23562000; Email: Leara91@gmail.com
    • Contact: Nasser Aghdami, MD,PhD; Phone Number: (+98)23562000; Email: nasser.aghdami@royaninstitute.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

inclusion criteria:

• Non-united fracture of tibial midshaft at X-ray.
• Non-united gap less than 1cm.
• Fracture has fixed by closed intramedullary rod.
• Hypotrophic type.
• At least 6 months after initial surgery.
• Patient informed consent.

Exclusion criteria:

• Infected nonunion
• Multiple major fracture
• Non treated major fracture
• malignancy
• Pregnancy or lactating
• Uncontrolled chronic diseases, such as: diabetes mellitus, hypertension, renal diseases, liver diseases, thyroid diseases, heart diseases, blood diseases, etc.
• Steroid usage.
• Positive test for HIV and/or HBS and/or HBC and/or HTLV (1,2)
• Fracture site more than 1 cm.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSC recipients; The patients with nonunion fracture who underwent percutaneous implantation of bone marrow derived mesenchymal stem cells in combination with platelet lysate product.	Biological: Percutaneous injection; percutanous implantation of bone marrow derived mesenchymal stromal cells in patients with nonunion fracture.
Placebo Comparator: Placebo; The patients with nonunion fracture who underwent percutaneous injection of placebo.	Other: Percutaneous injection; Percutaneous implantation of placebo in patients with nonunion fracture.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical union	- Clinical union is defined as an asymptomatic patient who was able to fully bear weight on the injured leg	3months
Radiological healing	- radiographic fracture healing is defined by bone continuity (bony bridging) present in three out of four cortices in two projections (anterior-posterior & lateral x-rays), assessed by a blinded senior orthopedic surgeon. CT scan, for confirm the results - radiolographic fracture healing is defined by bone continuity (bony bridging) present in three out of four cortices in two projections (anterior-posterior & lateral x-rays), assessed by a blinded senior orthopedic surgeon. CT scan, for confirm the results - radiolographic fracture healing is defined by bone continuity (bony bridging) present in three out of four cortices in two projections (anterior-posterior & lateral x-rays), assessed by a blinded senior orthopedic surgeon. CT scan, for confirm the results	1week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain	The pain relief as measured by Visual Analogue Scale (VAS) 3 months after cell injection	3months
Quality of life	Evaluation the patients' quality of life with Visual Analogue Score (VAS) 3months after cell transplantation.	3months
Walking distance	Walking distance changes as measured by walking on treadmill 3 months after cell injection.	3months

Collaborators and Investigators

• Sponsor: Royan Institute
• Investigators: Study Director: Nasser Aghdami, MD,PhD, Head of Regenerative medicine department and cell therapy center of Royan Institute; Study Director: Mohammad Razi, MD, Department of orthopedic surgery, Tehran university of medical science, Tehran, Iran; Principal Investigator: Mohsen Emadedin, MD, Cell therapy center of Royan Institute; Principal Investigator: Narges Labibzadeh, MD, Department of Regenerative Medicine and cell therapy center, Royan Institute

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Anticipated): April 1, 2017
• Study Completion (Anticipated): August 1, 2017

Study Registration Dates

• First Submitted: May 5, 2015
• First Submitted That Met QC Criteria: May 19, 2015
• First Posted (Estimate): May 20, 2015

Study Record Updates

• Last Update Posted (Estimate): October 30, 2015
• Last Update Submitted That Met QC Criteria: October 29, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: bone marrow; Autologous; mesenchymal; nonunion fracture; stromal cell; platelet lysate product
• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone
• Other Study ID Numbers: Royan-Bone-013