NCT01842477

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started May 2013

Typical duration for phase_2

Geographic Reach
4 countries

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 19, 2013

Completed
10 days until next milestone

First Posted

Study publicly available on registry

April 29, 2013

Completed
2 days until next milestone

Study Start

First participant enrolled

May 1, 2013

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 5, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 5, 2016

Completed
Last Updated

June 4, 2026

Status Verified

November 1, 2017

Enrollment Period

2.8 years

First QC Date

April 19, 2013

Last Update Submit

June 2, 2026

Conditions

Delayed Union After Fracture of Humerus, Tibial or Femur

Outcome Measures

Primary Outcomes (1)

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

    At 6 weeks, 12 weeks, 24 weeks and 52 weeks after the implantation surgery

Secondary Outcomes (5)

  • Number of patients with proven bone healing

    6 weeks, 12 weeks, and 24 weeks after the implantation surgery

  • Amount of radiological callus

    6 weeks, 12 weeks, and 24 weeks after the implantation surgery

  • Clinical consolidation

    6 weeks, 12 weeks, and 24 weeks after implantation surgery

  • No reoperation done or scheduled

    24 weeks after implantation surgery

  • Changes in serum levels of bone turnover markers

    6 weeks, 12 weeks, and 24 weeks after the implantation surgery

Study Arms (1)

Implantation surgery

EXPERIMENTAL

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

Biological: Implantation of bone substitute plus autologous cultured mesenchymal cells

Interventions

Implantation of bone substitute plus autologous cultured mesenchymal cellsBIOLOGICAL

Implantation surgery of a synthetic bone substitute associated with autologous bone marrow cells expanded

Implantation surgery

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • 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)
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Depatment of Orthopaedic Surgery, Hôpital Henri Mondor

Créteil, 94000, France

Location

Department of Orthopaedic Surgery, CHRU Tours

Tours, 37044, France

Location

Department of Orthopaedic Trauma, University of Ulm

Ulm, 89081, Germany

Location

Istituto Ortopedico Rizzoli, Bologna

Bologna, 40136, Italy

Location

Servicio de Cirugía Ortopédica y Traumatología "A", Hospital La Paz

Madrid, 28046, Spain

Location

Related Publications (2)

  • Gomez-Barrena E, Rosset P, Gebhard F, Hernigou P, Baldini N, Rouard H, Sensebe L, Gonzalo-Daganzo RM, Giordano R, Padilla-Eguiluz N, Garcia-Rey E, Cordero-Ampuero J, Rubio-Suarez JC, Stanovici J, Ehrnthaller C, Huber-Lang M, Flouzat-Lachaniette CH, Chevallier N, Donati DM, Ciapetti G, Fleury S, Fernandez MN, Cabrera JR, Avendano-Sola C, Montemurro T, Panaitescu C, Veronesi E, Rojewski MT, Lotfi R, Dominici M, Schrezenmeier H, Layrolle P. Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial. Biomaterials. 2019 Mar;196:100-108. doi: 10.1016/j.biomaterials.2018.03.033. Epub 2018 Mar 19.

    PMID: 29598897RESULT

  • Granchi D, Gomez-Barrena E, Rojewski M, Rosset P, Layrolle P, Spazzoli B, Donati DM, Ciapetti G. Changes of Bone Turnover Markers in Long Bone Nonunions Treated with a Regenerative Approach. Stem Cells Int. 2017;2017:3674045. doi: 10.1155/2017/3674045. Epub 2017 Jun 20.

    PMID: 28744314RESULT

Related Links

Study Officials

  • Enrique Gomez Barrena

    Universidad Autonoma de Madrid

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 19, 2013

First Posted

April 29, 2013

Study Start

May 1, 2013

Primary Completion

February 5, 2016

Study Completion

February 5, 2016

Last Updated

June 4, 2026

Record last verified: 2017-11

Locations

DE(1)FR(2)ES(1)IT(1)