Effectiveness of Adipose Tissue Derived Mesenchymal Stem Cells as Osteogenic Component in Composite Grafts

NCT01532076 | Terminated Phase 2

• 1 other identifier: 348/10
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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

Conditions

Osteoporotic Fractures

Keywords

osteoporosis; prox. humeral fracture; geriatric trauma; mesenchymal stem cells

Outcome Measures

Primary Outcomes (1)

• 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

  12 months postoperative

Secondary Outcomes (5)

• Functional outcome 6 weeks, 6 and 12 months after fixation

  12 months postoperative

• Safety

  12 months postoperative

• bone mineral density

  12 months postoperative

• Histology

  12 months postoperative

• Dose-response

  12 months postoperative

Study Arms (2)

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;

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.

Procedure: Acellular composite graft augmentation

Interventions

Cellularized composite graft augmentation PROCEDURE

liposuction, cell isolation, embedding of SVF cells in fibrin gel, wrapping around hydroxyapatite granules

Also known as: Cellution/CR800, Cytori, US, Tisseel, Baxter, Germany, Actifuse Microgranules, Apatech, Germany

cellularized composite graft augmentation

Acellular composite graft augmentation PROCEDURE

Open reduction and internal fixation using acellular augmentation with fibrin embedded granulated hydroxyapatite

Also known as: Tisseel, Baxter, Germany, Actifuse Microgranules, Apatech, Germany

Control acellular composite graft augmentation

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel

Basel, Canton of Basel-City, 4031, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 35727196 DERIVED

MeSH Terms

Conditions

Osteoporotic Fractures; Osteoporosis

Interventions

Fibrin Tissue Adhesive

Condition Hierarchy (Ancestors)

Fractures, Bone; Wounds and Injuries; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Fibrin; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Franziska Saxer, MD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

• Marcel Jakob, MD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2012
• First Posted: February 13, 2012
• Study Start: June 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: September 17, 2014

Record last verified: 2014-09

Locations

CH (1)