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A Comparative Study of 2 Doses of BM Autologous H-MSC+Biomaterial vs Iliac Crest AutoGraft for Bone Healing in Non-Union (ORTHOUNION)

Primary Purpose

Non Union Fracture

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Cultured Mesenchymal Stem Cells
Autologous iliac crest graft
Sponsored by
Universidad Autonoma de Madrid
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Union Fracture focused on measuring Non-union, Advanced therapies, Mesenchymal stem cells, Long bone

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age 18 years and older, both sexes
  2. Traumatic isolated closed or open Gustilo I and II, IIIA and IIIB humerus, tibial or femur diaphyseal or metaphysodiaphyseal fracture with a status of atrophic, oligotrophic or normotrophic non-union.
  3. Able to understand, accept and sign informed consent
  4. Medical health coverage
  5. Able to understand and accept the study constraints

Exclusion Criteria:

  1. Hypertrophic non-unions
  2. Segmental bone loss requiring specific therapy (bone transport, vascularized graft, large structural allograft, megaprosthesis, etc)
  3. Unrecovered vascular or neural injury
  4. Other fractures causing interference with weight bearing
  5. Visceral injuries or diseases interfering with callus formation (severe cranioencephalic trauma, etc.)
  6. Active infection of any location and aetiology
  7. Surgical contraindication of any cause
  8. Pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control.
  9. Malignant tumour (past history or concurrent disease)(except carcinoma in situ or basalioma in remission)
  10. History of bone harvesting on iliac crest contraindicating new iliac crest bone graft harvesting or bone marrow collection
  11. Insulin dependent diabetes
  12. Any evidence (confirmed by PCR) of active infection with HIV, Hepatitis B or Hepatitis C infection
  13. Any evidence of Syphilis
  14. Known allergies to products involved in the production process of MSC
  15. Corticoid or immunosuppressive therapy more than one week in the three months prior to study inclusion
  16. Autoimmune inflammatory disease
  17. Current treatment by biphosphonates not stopped three months prior to study inclusion
  18. Impossibility to meet at the appointments for the follow up
  19. Participation in another therapeutic trial in the previous 3 months
  20. Second non-union in case of bilateral or multiple non-unions (only one non-union per patient will be included in the trial)

Sites / Locations

  • CHU Clermont-Ferrand
  • Department of Orthopaedic Surgery, Hospital Henri Mondor
  • Department of Orthopaedic Surgery, CHU Nantes
  • Department of Orthopaedic Surgery Toulouse University Hospital
  • Department of Orthopaedic Surgery, CHU Tours
  • Universitätsklinikum Frankfurt, Department of Trauma, Hand and Reconstructive Surgery
  • Universitätsklinikum Freiburg, Klinik für Orthopädie und Unfallchirurgie
  • Universitätsklinikum München
  • Department of Orthopaedic Trauma, University of Ulm
  • Istituto Ortopedico Rizzoli, SSD Fisiopatologia Ortopedica e Medicina Rigenerativa
  • Arienda Spedali Civili di Brescia II Ortopedia e Traumatologia
  • Istituto Ortopedico Galeazzi, Chirugia dell´Anca l
  • Hospital U. Puerta de Hierro-Majadahonda, Servicio de Cirugía Ortopédica y Traumatología
  • Hospital Clínica San Carlos, Servicio de Cirugía Ortopédica y Traumatología
  • Hospital U. 12 de Octubre, Servicio de Cirugía Ortopédica y Traumatología
  • Hospital U. Gregorio Marañon, Servicio de Cirugía Ortopédica y Traumatología
  • Hospital U. La Princesa, Servicio de CirugíaOrtopédica y Traumatología
  • Hospital Universitario Ramón y Cajal
  • Servicio de Cirugía Ortopédica y Traumatología "A", Hospital La Paz

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

hBM-MSCs-Low Dose

hBM-MSCs-High Dose

Autologous iliac crest graft

Arm Description

Autologous Cultured Mesenchymal Stem Cells +Biomaterial (Low Dose): 100x106 cells

Autologous Cultured Mesenchymal Stem Cells+Biomaterial (High Dose): 200x106 cells

Autologous Iliac Crest Grafting

Outcomes

Primary Outcome Measures

Bone consolidation
The percentage of bone consolidation in the comparator treatment arm ( iliac crest autograft) and experimental treatment arm (mesenchymal cells).

Secondary Outcome Measures

Bone consolidation
To compare bone consolidation between the experimental arms and the comparator
Radiological Bone consolidation
To compare bone consolidation, using the REBORNE scale, between the experimental arms and the comparator. The REBORNE scale is an ad-hoc and validated scale, developed by Gomez-Barrena et al. (article currently under preparation) as a modification of the RUST score (Whelan, 2010; Journal of Trauma). In the REBORNE scale, the presence/absence of radiological consolidation is evaluated on a total of 4 cortices. Score range from 0 (no bone callus visible) to 4 (callus present with same density as cortical). The total score will be recorded.
Level of Pain
To compare level of pain (by Numeric Rating Scale [NRS]) between the experimental arms and the comparator. The NRS is a scale that rates the patient´s pain from 0-10 (0= no pain, 10= worst pain), at the time of the visit.
Complications
To compare the rate of complications between the experimental arms and the comparator
Health status
To compare the health status (by using the Short Form-36 Health Questionnaire) between treatment arms. The SF-36 questionnaire is a validated, widely used patient-reported health survey which measures their physical and mental health status. It consists of 36 questions organized in 8 dimensions. The total score will be recorded.

Full Information

First Posted
October 25, 2017
Last Updated
May 26, 2022
Sponsor
Universidad Autonoma de Madrid
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1. Study Identification

Unique Protocol Identification Number
NCT03325504
Brief Title
A Comparative Study of 2 Doses of BM Autologous H-MSC+Biomaterial vs Iliac Crest AutoGraft for Bone Healing in Non-Union
Acronym
ORTHOUNION
Official Title
A Multi-centre, Open-label, Randomized, Comparative Clinical Trial of Two Doses of Bone Marrow Autologous MSC+ Biomaterial vs Iliac Crest Autologous Graft, for Bone Healing in Non-union After Long Bone Fractures
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 5, 2017 (Actual)
Primary Completion Date
December 30, 2022 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Universidad Autonoma de Madrid

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
ORTHOUNION is a multi-centre, open, comparative, randomized, clinical trial with three parallel arms that aims to compare the efficacy of three treatments to enhance bone healing in patients with long bone non-union.
Detailed Description
Bone injuries represent an important world medical problem producing significant healthcare and societal expenditure. While most bone injuries are not severe and are capable of healing through bone regeneration by natural callus formation with standard treatments, severe bone injuries may not heal, becoming an important unmet clinical need. Non-unions, or pseudarthrosis, may occur in 5% to 20% of long-bone fractures that fail to heal properly after more than 6 months, with morbidity, prolonged hospitalization, and increased expenses. The most commonly accepted standard augmentation to procure fracture and non-union healing consists of autologous bone grafting, obtained from the same patient in a different surgical site and transplanted to the reconstruction site. However, autologous bone grafting has some drawbacks (such as persistent pain, scar, late recovery, limited amount of bone, etc) and a limited regeneration efficacy (success rate of about 74%) and high societal cost. Culture-expanded autologous MSCs combined with biphasic calcium phosphate (BCP) biomaterial granules have been claimed as a solid regenerative medicine alternative to autologous bone grafting in non-unions, although current data are limited. In this context, the ORTHOUNION initiative focuses on the opportunity to test the hypothesis of superiority of MSC, the investigational ATMP, versus the currently accepted standard therapy, iliac crest bone autograft to biologically augment surgical treatment of long-bone non-unions.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Union Fracture
Keywords
Non-union, Advanced therapies, Mesenchymal stem cells, Long bone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
46 (Actual)

8. Arms, Groups, and Interventions

Arm Title
hBM-MSCs-Low Dose
Arm Type
Experimental
Arm Description
Autologous Cultured Mesenchymal Stem Cells +Biomaterial (Low Dose): 100x106 cells
Arm Title
hBM-MSCs-High Dose
Arm Type
Experimental
Arm Description
Autologous Cultured Mesenchymal Stem Cells+Biomaterial (High Dose): 200x106 cells
Arm Title
Autologous iliac crest graft
Arm Type
Active Comparator
Arm Description
Autologous Iliac Crest Grafting
Intervention Type
Biological
Intervention Name(s)
Cultured Mesenchymal Stem Cells
Intervention Description
Cultured Mesenchymal Stem Cells obtained from expanded bone marrow
Intervention Type
Procedure
Intervention Name(s)
Autologous iliac crest graft
Intervention Description
Autologous iliac crest grafting
Primary Outcome Measure Information:
Title
Bone consolidation
Description
The percentage of bone consolidation in the comparator treatment arm ( iliac crest autograft) and experimental treatment arm (mesenchymal cells).
Time Frame
12 months after treatment
Secondary Outcome Measure Information:
Title
Bone consolidation
Description
To compare bone consolidation between the experimental arms and the comparator
Time Frame
6 and 24 months
Title
Radiological Bone consolidation
Description
To compare bone consolidation, using the REBORNE scale, between the experimental arms and the comparator. The REBORNE scale is an ad-hoc and validated scale, developed by Gomez-Barrena et al. (article currently under preparation) as a modification of the RUST score (Whelan, 2010; Journal of Trauma). In the REBORNE scale, the presence/absence of radiological consolidation is evaluated on a total of 4 cortices. Score range from 0 (no bone callus visible) to 4 (callus present with same density as cortical). The total score will be recorded.
Time Frame
6, 12 and 24 months
Title
Level of Pain
Description
To compare level of pain (by Numeric Rating Scale [NRS]) between the experimental arms and the comparator. The NRS is a scale that rates the patient´s pain from 0-10 (0= no pain, 10= worst pain), at the time of the visit.
Time Frame
6, 12 and 24 months
Title
Complications
Description
To compare the rate of complications between the experimental arms and the comparator
Time Frame
6, 12 and 24 months
Title
Health status
Description
To compare the health status (by using the Short Form-36 Health Questionnaire) between treatment arms. The SF-36 questionnaire is a validated, widely used patient-reported health survey which measures their physical and mental health status. It consists of 36 questions organized in 8 dimensions. The total score will be recorded.
Time Frame
6, 12 and 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18 years and older, both sexes Traumatic isolated closed or open Gustilo I and II, IIIA and IIIB humerus, tibial or femur diaphyseal or metaphysodiaphyseal fracture with a status of atrophic, oligotrophic or normotrophic non-union. Able to understand, accept and sign informed consent Medical health coverage Able to understand and accept the study constraints Exclusion Criteria: Hypertrophic non-unions Segmental bone loss requiring specific therapy (bone transport, vascularized graft, large structural allograft, megaprosthesis, etc) Unrecovered vascular or neural injury Other fractures causing interference with weight bearing Visceral injuries or diseases interfering with callus formation (severe cranioencephalic trauma, etc.) Active infection of any location and aetiology Surgical contraindication of any cause Pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control. Malignant tumour (past history or concurrent disease)(except carcinoma in situ or basalioma in remission) History of bone harvesting on iliac crest contraindicating new iliac crest bone graft harvesting or bone marrow collection Insulin dependent diabetes Any evidence (confirmed by PCR) of active infection with HIV, Hepatitis B or Hepatitis C infection Any evidence of Syphilis Known allergies to products involved in the production process of MSC Corticoid or immunosuppressive therapy more than one week in the three months prior to study inclusion Autoimmune inflammatory disease Current treatment by biphosphonates not stopped three months prior to study inclusion Impossibility to meet at the appointments for the follow up Participation in another therapeutic trial in the previous 3 months Second non-union in case of bilateral or multiple non-unions (only one non-union per patient will be included in the trial)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Enrique Gomez-Barrena, Prof
Organizational Affiliation
UAM
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Clermont-Ferrand
City
Clermont-Ferrand
Country
France
Facility Name
Department of Orthopaedic Surgery, Hospital Henri Mondor
City
Créteil
Country
France
Facility Name
Department of Orthopaedic Surgery, CHU Nantes
City
Nantes
Country
France
Facility Name
Department of Orthopaedic Surgery Toulouse University Hospital
City
Toulouse
Country
France
Facility Name
Department of Orthopaedic Surgery, CHU Tours
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Universitätsklinikum Frankfurt, Department of Trauma, Hand and Reconstructive Surgery
City
Frankfurt
Country
Germany
Facility Name
Universitätsklinikum Freiburg, Klinik für Orthopädie und Unfallchirurgie
City
Freiburg
Country
Germany
Facility Name
Universitätsklinikum München
City
Munich
Country
Germany
Facility Name
Department of Orthopaedic Trauma, University of Ulm
City
Ulm
ZIP/Postal Code
8907581
Country
Germany
Facility Name
Istituto Ortopedico Rizzoli, SSD Fisiopatologia Ortopedica e Medicina Rigenerativa
City
Bologna
ZIP/Postal Code
40136
Country
Italy
Facility Name
Arienda Spedali Civili di Brescia II Ortopedia e Traumatologia
City
Brescia
Country
Italy
Facility Name
Istituto Ortopedico Galeazzi, Chirugia dell´Anca l
City
Milano
Country
Italy
Facility Name
Hospital U. Puerta de Hierro-Majadahonda, Servicio de Cirugía Ortopédica y Traumatología
City
Majadahonda
State/Province
Madrid
Country
Spain
Facility Name
Hospital Clínica San Carlos, Servicio de Cirugía Ortopédica y Traumatología
City
Madrid
Country
Spain
Facility Name
Hospital U. 12 de Octubre, Servicio de Cirugía Ortopédica y Traumatología
City
Madrid
Country
Spain
Facility Name
Hospital U. Gregorio Marañon, Servicio de Cirugía Ortopédica y Traumatología
City
Madrid
Country
Spain
Facility Name
Hospital U. La Princesa, Servicio de CirugíaOrtopédica y Traumatología
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Ramón y Cajal
City
Madrid
Country
Spain
Facility Name
Servicio de Cirugía Ortopédica y Traumatología "A", Hospital La Paz
City
Madrid
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
29535772
Citation
Gomez-Barrena E, Padilla-Eguiluz NG, Avendano-Sola C, Payares-Herrera C, Velasco-Iglesias A, Torres F, Rosset P, Gebhard F, Baldini N, Rubio-Suarez JC, Garcia-Rey E, Cordero-Ampuero J, Vaquero-Martin J, Chana F, Marco F, Garcia-Coiradas J, Caba-Dessoux P, de la Cuadra P, Hernigou P, Flouzat-Lachaniette CH, Gouin F, Mainard D, Laffosse JM, Kalbitz M, Marzi I, Sudkamp N, Stockle U, Ciapetti G, Donati DM, Zagra L, Pazzaglia U, Zarattini G, Capanna R, Catani F. A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol. Stem Cells Int. 2018 Feb 22;2018:6025918. doi: 10.1155/2018/6025918. eCollection 2018.
Results Reference
background
Links:
URL
http://orthounion.eu
Description
Webpage of the Orthounion Study

Learn more about this trial

A Comparative Study of 2 Doses of BM Autologous H-MSC+Biomaterial vs Iliac Crest AutoGraft for Bone Healing in Non-Union

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