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Evaluation of Efficacy and Safety of Autologous MSCs Combined to Biomaterials to Enhance Bone Healing (OrthoCT1)

Primary Purpose

Delayed Union After Fracture of Humerus, Tibial or Femur

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Implantation of bone substitute plus autologous cultured mesenchymal cells
Sponsored by
Institut National de la Santé Et de la Recherche Médicale, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Delayed Union After Fracture of Humerus, Tibial or Femur

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age 18 to 65, both sexes
  • Traumatic isolated closed or open Gustilo I and II humerus, tibial or femur diaphyseal or metaphyseal-diaphyseal fracture status delayed union or non-union
  • At least 3 months from acute fracture
  • Able to provide informed consent, and signed informed consent
  • Patients (by themselves) should have medical health care coverage to be included in a research study
  • Able to understand and accept the study constraints

Exclusion Criteria:

  • Pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control
  • Participation in another therapeutic trial in the previous 3 months
  • Delayed union or non-union related to iatrogeny
  • Segmental bone loss requiring specific therapy (bone transport, large structural allograft, megaprosthesis, etc)
  • Vascular or neural injury
  • Other fractures causing interference with weight bearing
  • Acute persistent chronic bacterial infections such as brucellosis, typhus, leprosy, relapsing fever, melioidosis and tularemia
  • Visceral injuries of diseases interfering with callus formation (cranioencephalic trauma, etc.)
  • History of bone harvesting on iliac crest contraindicating bone-marrow aspiration
  • Corticoid or immunosuppressive therapy more than one week in the three months prior to study inclusion
  • History of prior or concurrent diagnosis of HIV-, Syphilis, Hepatitis-B- or Hepatitis-C-infection (confirmed by serology or PCR)
  • History of neoplasia or current neoplasia in any organ
  • Subject legally protected, under legal guardianship, deprived of their liberty by judicial or administrative decision, subject of psychiatric care, or admission to a health facility.
  • Impossibility to meet at the appointments for the follow up
  • Insulin dependent diabetes
  • Obesity (BMI > 30)
  • Autoimmune inflammatory disease
  • Current treatment by biphosphonate or stopped in the three months prior to study inclusion.

Sites / Locations

  • Depatment of Orthopaedic Surgery, Hôpital Henri Mondor
  • Department of Orthopaedic Surgery, CHRU Tours
  • Department of Orthopaedic Trauma, University of Ulm
  • Istituto Ortopedico Rizzoli, Bologna
  • Servicio de Cirugía Ortopédica y Traumatología "A", Hospital La Paz

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Implantation surgery

Arm Description

All the patients will have the implantation surgery. This trial is a one-arm study.

Outcomes

Primary Outcome Measures

Complication rate as percentage of patients with local complications regarding the non-union treatment in the follow-up

Secondary Outcome Measures

Number of patients with proven bone healing
Amount of radiological callus
Clinical consolidation
No reoperation done or scheduled
Changes in serum levels of bone turnover markers

Full Information

First Posted
April 19, 2013
Last Updated
November 29, 2017
Sponsor
Institut National de la Santé Et de la Recherche Médicale, France
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1. Study Identification

Unique Protocol Identification Number
NCT01842477
Brief Title
Evaluation of Efficacy and Safety of Autologous MSCs Combined to Biomaterials to Enhance Bone Healing
Acronym
OrthoCT1
Official Title
Evaluation of Efficacy and Safety of Autologous MSCs Combined to Biomaterials to Enhance Bone Healing in Patients With Delayed Consolidation After Long Bone Fracture Requiring Graft Apposition or Alternative Orthobiologics
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
May 2013 (undefined)
Primary Completion Date
February 5, 2016 (Actual)
Study Completion Date
February 5, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut National de la Santé Et de la Recherche Médicale, France

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Bone grafting is widely used in hospitals to repair injured, aged or diseased skeletal tissue. In Europe, about one million patients encounter a surgical bone reconstruction annually and the numbers are increasing due to our ageing population. Bone grafting intends to facilitate bone healing through osteogenesis (i.e. bone generation) at the site of damage, but this is only attained presently by including cells capable of forming bone into the augmentation. Bone autograft is the safest and most effective grafting procedure, since it contains patient's own bone growing cells (to enhance osteogenesis) and proteins (to enhance osteoinduction), and it providing a scaffold for the new bone to grow into (osteoconduction). However, bone autograft is limited in quantity (about 20 cc) and its harvesting (e.g. from the iliac crest) represents an additional surgical intervention, with frequent consequent pain and complications. We hypothesize that using autologous bone marrow cells expanded in GMP facility surgically implanted with synthetic bone substitutes contribute to the resolution of the health and socioeconomic complications of delayed union or non-union after diaphyseal and metaphyseal-diaphyseal fractures with safety and efficacy.
Detailed Description
Tissue engineering combines bone marrow cells or mesenchymal stem cells (MSCs), synthetic scaffolds and molecular signals (growth or differentiating factors) in order to form hybrids constructs. For bone reconstruction purposes, human MSCs have been seeded and cultured on porous calcium phosphate ceramics in osteogenic media. Some clinical studies with low numbers of patients have been reported using this approach but the outcomes were inconsistent with low efficacy in bone regeneration. The reasons of the limited clinical success may be due to several bottlenecks in the multidisciplinary field of bone tissue engineering. The association in vitro of biomaterials and osteoprogenitor cells raises technical challenges and regulatory and ethic issues for the implementation of clinical trials, whereas the expansion of MSCs is now possible in GMP Facility. The expected results are to obtain bone consolidation thus healing of delayed union or non-union, as proven by imaging techniques, without using bone graft. This will prove the efficacy of the proposed IMP based on pluripotent MSCs expanded in a GMP facility and mixed with granulated biphasic calcium phosphate in the surgical setting before implantation. No expected complications related to the procedure are expected. Changes in serum levels of bone turnover markers will be described.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Delayed Union After Fracture of Humerus, Tibial or Femur

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Implantation surgery
Arm Type
Experimental
Arm Description
All the patients will have the implantation surgery. This trial is a one-arm study.
Intervention Type
Procedure
Intervention Name(s)
Implantation of bone substitute plus autologous cultured mesenchymal cells
Intervention Description
Implantation surgery of a synthetic bone substitute associated with autologous bone marrow cells expanded
Primary Outcome Measure Information:
Title
Complication rate as percentage of patients with local complications regarding the non-union treatment in the follow-up
Time Frame
At 6 weeks, 12 weeks, 24 weeks and 52 weeks after the implantation surgery
Secondary Outcome Measure Information:
Title
Number of patients with proven bone healing
Time Frame
6 weeks, 12 weeks, and 24 weeks after the implantation surgery
Title
Amount of radiological callus
Time Frame
6 weeks, 12 weeks, and 24 weeks after the implantation surgery
Title
Clinical consolidation
Time Frame
6 weeks, 12 weeks, and 24 weeks after implantation surgery
Title
No reoperation done or scheduled
Time Frame
24 weeks after implantation surgery
Title
Changes in serum levels of bone turnover markers
Time Frame
6 weeks, 12 weeks, and 24 weeks after the implantation surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18 to 65, both sexes Traumatic isolated closed or open Gustilo I and II humerus, tibial or femur diaphyseal or metaphyseal-diaphyseal fracture status delayed union or non-union At least 3 months from acute fracture Able to provide informed consent, and signed informed consent Patients (by themselves) should have medical health care coverage to be included in a research study Able to understand and accept the study constraints Exclusion Criteria: Pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control Participation in another therapeutic trial in the previous 3 months Delayed union or non-union related to iatrogeny Segmental bone loss requiring specific therapy (bone transport, large structural allograft, megaprosthesis, etc) Vascular or neural injury Other fractures causing interference with weight bearing Acute persistent chronic bacterial infections such as brucellosis, typhus, leprosy, relapsing fever, melioidosis and tularemia Visceral injuries of diseases interfering with callus formation (cranioencephalic trauma, etc.) History of bone harvesting on iliac crest contraindicating bone-marrow aspiration Corticoid or immunosuppressive therapy more than one week in the three months prior to study inclusion History of prior or concurrent diagnosis of HIV-, Syphilis, Hepatitis-B- or Hepatitis-C-infection (confirmed by serology or PCR) History of neoplasia or current neoplasia in any organ Subject legally protected, under legal guardianship, deprived of their liberty by judicial or administrative decision, subject of psychiatric care, or admission to a health facility. Impossibility to meet at the appointments for the follow up Insulin dependent diabetes Obesity (BMI > 30) Autoimmune inflammatory disease Current treatment by biphosphonate or stopped in the three months prior to study inclusion.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Enrique Gomez Barrena
Organizational Affiliation
Universidad Autonoma de Madrid
Official's Role
Principal Investigator
Facility Information:
Facility Name
Depatment of Orthopaedic Surgery, Hôpital Henri Mondor
City
Créteil
ZIP/Postal Code
94000
Country
France
Facility Name
Department of Orthopaedic Surgery, CHRU Tours
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Department of Orthopaedic Trauma, University of Ulm
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Istituto Ortopedico Rizzoli, Bologna
City
Bologna
ZIP/Postal Code
40136
Country
Italy
Facility Name
Servicio de Cirugía Ortopédica y Traumatología "A", Hospital La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain

12. IPD Sharing Statement

Links:
URL
http://www.reborne.org/
Description
Related Info

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Evaluation of Efficacy and Safety of Autologous MSCs Combined to Biomaterials to Enhance Bone Healing

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