Clinical trial NCT01532076: Effectiveness of Adipose Tissue Derived Mesenchymal Stem Cells as Osteogenic Component in Composite Grafts
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Osteoporotic Fractures
Keywords: osteoporosis
prox. humeral fracture
geriatric trauma
mesenchymal stem cells
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2012-02-13
Enrollment: 8
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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


Eligibility criteria: Inclusion Criteria:

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
* age \> 50 years
* postmenopausal status (i.e. 12 continuous month without menstruation)
* informed consent in surgery and study participation

Exclusion Criteria:

* 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

Primary outcomes:
measure: Development of secondary dislocation within 12 months postoperative
timeFrame: 12 months postoperative
Secondary outcomes:
measure: Functional outcome 6 weeks, 6 and 12 months after fixation
timeFrame: 12 months postoperative
measure: Safety
timeFrame: 12 months postoperative
measure: bone mineral density
timeFrame: 12 months postoperative
measure: Histology
timeFrame: 12 months postoperative
measure: Dose-response
timeFrame: 12 months postoperative
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
state: Basel-Stadt
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Franziska Saxer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Basel, Switzerland
name: Marcel Jakob, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.