Osteoporotic FracturesPhase 2ROBUSTNCT01532076
Effectiveness of Adipose Tissue Derived Mesenchymal Stem Cells as Osteogenic Component in Composite Grafts
A Phase 2 study testing Cellularized composite graft augmentation and Acellular composite graft augmentation in people with Osteoporotic Fractures, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
Failure rates of up to 30% are reported after proximal humeral fractures despite angular-stable devices. This may devastate not only the functional outcome but also the independence of elderly patients. To increase bone mineral density and thereby holding-strength augmentation is an option. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Osteoporotic Fractures
- What is being tested?
- Cellularized composite graft augmentation and Acellular composite graft augmentation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jun 2012to Sep 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Presentation with an isolated proximal humeral fracture after a low-energy trauma (e.g. falling from a standing position) and:
- indication for open reduction and internal fixation with a proximal humeral locking plate (PHILOS®, Synthes, Switzerland) after low energy trauma
- displacement of more than 1 cm between fragments and/or
- angulation of 45° or more between the fragments and/or
- dislocation of the greater tuberosity of 5 mm or more and/or
- patient specific factors like high functional demand etc
Show all 9Show fewer
- age > 50 years
- postmenopausal status (i.e. 12 continuous month without menstruation)
- informed consent in surgery and study participation
Who cannot join
- Psychiatric disorder severely impairing co-operation (dementia mini mental Status (MMS) <24, schizophrenia, major depression)
- Pathological fractures caused by other conditions
- Fracture-related nerve injury
- Malignancies under current treatment (i.e. chemotherapy, radiotherapy etc.)
- BMI <20 kg/m2
- Known hypersensitivity to one of the graft components
- Participation in a clinical trial within 3 month before enrolment
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Hospital Basel
Basel, Canton of Basel-City, 4031
About this study
Official title: Effectiveness of Adipose Tissue Derived Mesenchymal Stem Cells as Osteogenic Component in Composite Grafts Versus Acellular Bone Graft Substitutes for Augmentation in the Treatment of Proximal Humeral Fractures as Model for Fractures of Osteoporotic Bone - a Prospective Randomized First in Men Proof of Principle Trial
Failure rates of up to 30% are reported after proximal humeral fractures despite angular-stable devices. This may devastate not only the functional outcome but also the independence of elderly patients.
To increase bone mineral density and thereby holding-strength augmentation is an option. Autologous bone-graft, as current gold-standard, though is questionable in osteoporosis since osteoprogenitors are dysfunctional and the harvesting-morbidity considerable. Adipose tissue seems an alternative cell-source even in presence of osteoporosis.
Read more
Stromal vascular fraction (SVF) cells isolated from lipoaspirates display osteogenic and vasculogenic potential and can be harvested in high numbers. Expansion associated with costly good-manufacturers-practice facilities is avoidable, so are repeated interventions. These cells have been successfully used to generate osteogenic composite grafts with intrinsic vascularity in preclinical models.
For translation into clinical practice after a 20 patient external pilot a prospective randomized controlled trial with 270 patients is planned. For the trial lipoaspiration precedes open reduction and internal fixation in individuals over 60 years presenting with a proximal humeral fracture after low-energy trauma. Cells are isolated (Cellution®800/CRS) and wrapped around hydroxyapatite microgranules after embedding in a fibrin-gel for augmentation of the typical bone-void. Clinical/radiological follow-up is at 6 and 12 weeks for immediate complications and after 6, 9 and 12 months. Functional assessment is performed after 6 weeks, 6 and 12 months using the Quick-Dash- and Constant-Score.
The primary outcome is a reduction in secondary dislocation by 50% during the first postoperative year. Secondary dislocation is diagnosed on plain radiographs by an independent board certified radiologist specialised in musculoskeletal imaging if one or more of the following criteria are met:
- More than 20° varus collapse of the humeral head fragment in relation to the humeral shaft
- Screw penetration through the humeral head
- Conditions
- Osteoporotic Fractures
- Being tested
- Cellularized composite graft augmentation, Acellular composite graft augmentation
- Keywords
- osteoporosis, prox. humeral fracture, geriatric trauma, mesenchymal stem cells
- Medical subject headings
- Osteoporotic Fractures, Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cellularized composite graft augmentationProcedure or surgery
Also called Cellution/CR800, Cytori, US, Tisseel, Baxter, Germany, Actifuse Microgranules, Apatech, Germany
liposuction, cell isolation, embedding of SVF cells in fibrin gel, wrapping around hydroxyapatite granules
Acellular composite graft augmentationProcedure or surgery
Also called Tisseel, Baxter, Germany, Actifuse Microgranules, Apatech, Germany
Open reduction and internal fixation using acellular augmentation with fibrin embedded granulated hydroxyapatite
| Study group | Role | What they receive |
|---|---|---|
| cellularized composite graft augmentation | Experimental | lipoaspiration by experienced plastic surgeon, isolation of SVF cells using a Cellution/CR800® cell isolation device and single use kits (Cytori Therapeutics Inc., San Diego) during open reduction and internal fixation, augmentation of bone with cell-seeded bone graft substitute; Receives: Procedure: Cellularized composite graft augmentation |
| Control acellular composite graft augmentation | Active comparator | open reduction internal fixation (ORIF) of the fracture, augmentation with acellular bone graft substitute. Receives: Procedure: Acellular composite graft augmentation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Development of secondary dislocation within 12 months postoperative
Secondary dislocation within the first year postoperative on plain radiographs in ap. and Neer projections diagnosed by an independent radiologist specialized in musculoskeletal imaging in case of
- more than 20° varus collapse of the humeral head fragment in relation to the humeral shaft
- screw penetration through the humeral head
Measured: 12 months postoperative
Secondary outcomes (5)
Functional outcome 6 weeks, 6 and 12 months after fixation
Functional outcome 6 weeks, 6 and 12 months after fixation: the functional outcome will be recorded by the Quick Dash Score and the Constant at each follow up visit and compared between the two groups. Additionally, pain at either surgical site will be recorded via the visual analogue scale.
Measured: 12 months postoperative
Safety
safety: all adverse reactions will be recorded and analysed to assess the safety of the approach in a typical patient population.
Measured: 12 months postoperative
bone mineral density
bone mineral density: in case of implant removal (see below) a 100 mm3 bone biopsy will be taken from the grafted area and analysed with MicroCT (micro computed tomography) for bone mineral density.
Measured: 12 months postoperative
Histology
histological assessment of qualitative and quantitative bone formation: bone biopsies will - after MicroCT assessment - be decalcified and histologically analysed using standard techniques and image quantification
Measured: 12 months postoperative
Dose-response
establishment of a dose response relationship between number of implanted cells an bone quantity in microCT and histologically via image quantification: retrospectively the quantitative measures of bone formation will be correlated to the number of implanted cells and their clonogenicity
Measured: 12 months postoperative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2012 (estimated)
- Study startJun 2012
- Primary completionSep 2014
- Study completionSep 2014
Why it stopped: Slow recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Osteoporotic FracturesStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Franziska Saxer, MD, Principal investigator, University Hospital, Basel, SwitzerlandMarcel Jakob, MD, Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01532076
- Sponsor's protocol ID
- 348/10
- Acronym
- ROBUST
- Status last verified
- Sep 2014
- First submitted
- 5 Jan 2012
- Last updated
- 17 Sep 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Handoll HH, Elliott J, Thillemann TM, Aluko P, Brorson S. Interventions for treating proximal humeral fractures in adults. Cochrane Database Syst Rev. 2022 Jun 21;6(6):CD000434. doi: 10.1002/14651858.CD000434.pub5.
PubMed 35727196
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness of Adipose Tissue Derived Mesenchymal Stem Cells as Osteogenic Component in Composite Grafts Versus Acellular Bone Graft Substitutes for Augmentation in the Treatment of Proximal Humeral Fractures as Model for Fractures of Osteoporotic Bone - a Prospective Randomized First in Men Proof of Principle Trial
- ClinicalTrials.gov ID
- NCT01532076
- Acronym / sponsor ID
- ROBUST / 348/10
- Conditions
- Osteoporotic Fractures
- Keywords
- osteoporosis, prox. humeral fracture, geriatric trauma, mesenchymal stem cells
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 13 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Failure rates of up to 30% are reported after proximal humeral fractures despite angular-stable devices. This may devastate not only the functional outcome but also the independence of elderly patients.
To increase bone mineral density and thereby holding-strength augmentation is an option. Autologous bone-graft, as current gold-standard, though is questionable in osteoporosis since osteoprogenitors are dysfunctional and the harvesting-morbidity considerable. Adipose tissue seems an alternative cell-source even in presence of osteoporosis.
Stromal vascular fraction (SVF) cells isolated from lipoaspirates display osteogenic and vasculogenic potential and can be harvested in high numbers. Expansion associated with costly good-manufacturers-practice facilities is avoidable, so are repeated interventions. These cells have been successfully used to generate osteogenic composite grafts with intrinsic vascularity in preclinical models.
For translation into clinical practice after a 20 patient external pilot a prospective randomized controlled trial with 270 patients is planned. For the trial lipoaspiration precedes open reduction and internal fixation in individuals over 60 years presenting with a proximal humeral fracture after low-energy trauma. Cells are isolated (Cellution®800/CRS) and wrapped around hydroxyapatite microgranules after embedding in a fibrin-gel for augmentation of the typical bone-void. Clinical/radiological follow-up is at 6 and 12 weeks for immediate complications and after 6, 9 and 12 months. Functional assessment is performed after 6 weeks, 6 and 12 months using the Quick-Dash- and Constant-Score.
The primary outcome is a reduction in secondary dislocation by 50% during the first postoperative year. Secondary dislocation is diagnosed on plain radiographs by an independent board certified radiologist specialised in musculoskeletal imaging if one or more of the following criteria are met:
- More than 20° varus collapse of the humeral head fragment in relation to the humeral shaft
- Screw penetration through the humeral head
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| cellularized composite graft augmentation | Experimental | Procedure: Cellularized composite graft augmentationlipoaspiration by experienced plastic surgeon, isolation of SVF cells using a Cellution/CR800® cell isolation device and single use kits (Cytori Therapeutics Inc., San Diego) during open reduction and internal fixation, augmentation of bone with cell-seeded bone graft substitute; |
| Control acellular composite graft augmentation | Active comparator | Procedure: Acellular composite graft augmentationopen reduction internal fixation (ORIF) of the fracture, augmentation with acellular bone graft substitute. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Presentation with an isolated proximal humeral fracture after a low-energy trauma (e.g. falling from a standing position) and:
- indication for open reduction and internal fixation with a proximal humeral locking plate (PHILOS®, Synthes, Switzerland) after low energy trauma
- age > 50 years
- postmenopausal status (i.e. 12 continuous month without menstruation)
- informed consent in surgery and study participation
Key exclusion criteria (7 listed)
- Psychiatric disorder severely impairing co-operation (dementia mini mental Status (MMS) <24, schizophrenia, major depression)
- Pathological fractures caused by other conditions
- Fracture-related nerve injury
- Malignancies under current treatment (i.e. chemotherapy, radiotherapy etc.)
- BMI <20 kg/m2
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cellularized composite graft augmentationAlso: Cellution/CR800, Cytori, US, Tisseel, Baxter, Germany, Actifuse Microgranules, Apatech, Germanyliposuction, cell isolation, embedding of SVF cells in fibrin gel, wrapping around hydroxyapatite granules | Procedure or surgery | cellularized composite graft augmentation |
| Acellular composite graft augmentationAlso: Tisseel, Baxter, Germany, Actifuse Microgranules, Apatech, GermanyOpen reduction and internal fixation using acellular augmentation with fibrin embedded granulated hydroxyapatite | Procedure or surgery | Control acellular composite graft augmentation |
Primary outcome
Development of secondary dislocation within 12 months postoperative
Time frame: 12 months postoperative
Secondary dislocation within the first year postoperative on plain radiographs in ap. and Neer projections diagnosed by an independent radiologist specialized in musculoskeletal imaging in case of * more than 20° varus collapse of the humeral head fragment in relation to the humeral shaft * screw penetration through the humeral head
5 secondary outcomes
Functional outcome 6 weeks, 6 and 12 months after fixation
Time frame: 12 months postoperative
Safety
Time frame: 12 months postoperative
bone mineral density
Time frame: 12 months postoperative
Histology
Time frame: 12 months postoperative
Dose-response
Time frame: 12 months postoperative
Results and safety
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2014.
- Derived from this study: PubMed 35727196Handoll HH, Elliott J, Thillemann TM, Aluko P, Brorson S. Interventions for treating proximal humeral fractures in adults. Cochrane Database Syst Rev. 2022 Jun 21;6(6):CD000434. doi: 10.1002/14651858.CD000434.pub5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Franziska Saxer, MD principal investigator
University Hospital, Basel, Switzerland
Marcel Jakob, MD principal investigator
University Hospital, Basel, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cellularized composite graft augmentation and Acellular composite graft augmentation in people with Osteoporotic Fractures, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Development of secondary dislocation within 12 months postoperative (time frame: 12 months postoperative). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01532076, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2014.