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

December 2, 2024 updated by: Prof Enrique Gomez-Barrena, Universidad Autonoma de Madrid

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
46

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Clermont-Ferrand, France
        • Chu Clermont-Ferrand
      • Créteil, France
        • Department of Orthopaedic Surgery, Hospital Henri Mondor
      • Nantes, France
        • Department of Orthopaedic Surgery, CHU Nantes
      • Toulouse, France
        • Department of Orthopaedic Surgery Toulouse University Hospital
      • Tours, France, 37044
        • Department of Orthopaedic Surgery, CHU Tours
  • Germany
      • Frankfurt, Germany
        • Universitätsklinikum Frankfurt, Department of Trauma, Hand and Reconstructive Surgery
      • Freiburg, Germany
        • Universitätsklinikum Freiburg, Klinik für Orthopädie und Unfallchirurgie
      • Munich, Germany
        • Universitätsklinikum München
      • Ulm, Germany, 8907581
        • Department of Orthopaedic Trauma, University of Ulm
  • Italy
      • Bologna, Italy, 40136
        • Istituto Ortopedico Rizzoli, SSD Fisiopatologia Ortopedica e Medicina Rigenerativa
      • Brescia, Italy
        • Arienda Spedali Civili di Brescia II Ortopedia e Traumatologia
      • Milano, Italy
        • Istituto Ortopedico Galeazzi, Chirugia dell´Anca l
  • Spain
      • Madrid, Spain
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain
        • Hospital Clínica San Carlos, Servicio de Cirugía Ortopédica y Traumatología
      • Madrid, Spain
        • Hospital U. 12 de Octubre, Servicio de Cirugía Ortopédica y Traumatología
      • Madrid, Spain
        • Hospital U. Gregorio Marañon, Servicio de Cirugía Ortopédica y Traumatología
      • Madrid, Spain
        • Hospital U. La Princesa, Servicio de CirugíaOrtopédica y Traumatología
      • Madrid, Spain
        • Servicio de Cirugía Ortopédica y Traumatología "A", Hospital La Paz
    • Madrid
      • Majadahonda, Madrid, Spain
        • Hospital U. Puerta de Hierro-Majadahonda, Servicio de Cirugía Ortopédica y Traumatología

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: hBM-MSCs-Low Dose
Autologous Cultured Mesenchymal Stem Cells +Biomaterial (Low Dose): 100x106 cells
Biological: Cultured Mesenchymal Stem Cells
Cultured Mesenchymal Stem Cells obtained from expanded bone marrow
Experimental: hBM-MSCs-High Dose
Autologous Cultured Mesenchymal Stem Cells+Biomaterial (High Dose): 200x106 cells
Biological: Cultured Mesenchymal Stem Cells
Cultured Mesenchymal Stem Cells obtained from expanded bone marrow
Active Comparator: Autologous iliac crest graft
Autologous Iliac Crest Grafting
Procedure: Autologous iliac crest graft
Autologous iliac crest grafting

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Bone consolidation
Time Frame: 12 months after treatment
The percentage of bone consolidation in the comparator treatment arm ( iliac crest autograft) and experimental treatment arm (mesenchymal cells).
12 months after treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Bone consolidation
Time Frame: 6 and 24 months
To compare bone consolidation between the experimental arms and the comparator
6 and 24 months
Radiological Bone consolidation
Time Frame: 6, 12 and 24 months

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.
6, 12 and 24 months
Level of Pain
Time Frame: 6, 12 and 24 months

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.
6, 12 and 24 months
Complications
Time Frame: 6, 12 and 24 months
To compare the rate of complications between the experimental arms and the comparator
6, 12 and 24 months
Health status
Time Frame: 6, 12 and 24 months

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.
6, 12 and 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Universidad Autonoma de Madrid

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Enrique Gomez-Barrena, Prof, Universidad Autonoma de Madrid

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 5, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 17, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 15, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 25, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 25, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 30, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 4, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 2, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ORTHOUNION
  • 2015-000431-32 (EudraCT Number)
  • EUCTR2015-000431-32-ES (Registry Identifier: International Clinical Trials Registry Plataform)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Drug Interventions

Conditions

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