Using autologous mesenchymal stem cells (MSC) to treat human fractures

ISRCTN	ISRCTN09755245
DOI	https://doi.org/10.1186/ISRCTN09755245
Protocol serial number	G0900880
Sponsor	Joint UCLH and UCL Biomedical Research Unit (UK)
Funder	Medical Research Council (MRC) (UK) - Translational stem cell research programme: Response mode funding (ref: G0900880)

Submission date: 24/09/2009
Registration date: 13/01/2010
Last edited: 01/02/2016

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Musculoskeletal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

http://www.ctu.mrc.ac.uk/research_areas/study_details.aspx?s=87

Contact information

Prof David Marsh
Scientific

Professor of Clinical Orthopaedics
Royal National Orthopaedic Hospital
Institute of Orthopaedics and Musculoskeletal Science
Brockley Hill, Stanmore
London
HA7 4LP
United Kingdom

Study information

Primary study design	Interventional
Study design	Single-blind randomised controlled trial using minimisation
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Autologous cell therapy of fracture nonunion - cell phenotype as a predictor of outcome: a single blind randomised controlled trial
Study acronym	PACINO
Study objectives	The study questions are: 1. Do culture-expanded, autologous mesenchymal stem cells (MSC) stimulate healing of nonunions more effectively than unmodified bone marrow? 2. Does the magnitude of the regenerative response correlate with any identifiable phenotypic features of the implanted cells?
Ethics approval(s)	Outer North London Research Ethics Committee (REC) pending submission as of 29/09/2009. Planning to submit in October 2009.
Health condition(s) or problem(s) studied	Tibial nonunion fractures
Intervention	The standard treatment involves microdrilling holes across the docking site into which the patients own bone marrow is injected. This will be the treatment in the control arm of the trial. The study intervention will be the injection of the patients own mesenchymal stem cells (MSCs) into the microdrilled holes. Patients will receive one dose of either bone marrow or MSCs depending on whether they are in the control or intervention arm of the trial respectively. Treament is a single dose of 30 million MSCs at the docking site, the follow-up is for one year post-docking.
Intervention type	Procedure/Surgery
Primary outcome measure(s)	Change in bone mineral content (BMC) in a defined region of interest (ROI) around the docking site between 0 - 12 weeks after implantation, derived from computed tomography (CT) scans.
Key secondary outcome measure(s)	Imaging-based: 1. X-Rays: bridging of 3 out of 4 cortices 2. Finite Element Analysis (FEA) 3. Reliable Unwrapping Susceptibility Technique (RUST) scores The first antero-posterior (AP) and lateral radiographs will be taken prior to the segmental excision and after enrolment and then at 2 weekly intervals for 12 weeks with 3 radiographs in addition to standard care and then in line with standard care until week 52. Clinical outcomes: 4. Short-form Musculoskeletal Function Assessment (SMFA) 5. Pain (Visual Analogue Scale [VAS]) 6. Quality of life (36-item Short Form Health Survey [SF36]) and the need for re-operation Patients will be asked to complete SF36 and SMFA questionnaires at 2, 12 and 25 weeks and VAS pain scores will be given in line with standard care.
Completion date	31/12/2013
Reason abandoned (if study stopped)	Participant recruitment issue

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	60
Key inclusion criteria	1. Skeletally mature patients undergoing segmental excision of the tibia for nonunion followed by distraction osteogenesis and bone transport 2. Male and female patients 3. Over 18 years old with no upper age limit
Key exclusion criteria	1. Congenital disorders 2. Pregnant or lactating women 3. Metabolic bone disease or bone active drugs 4. Anticipated problems with maintaining follow-up
Date of first enrolment	01/01/2010
Date of final enrolment	31/12/2013

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Royal National Orthopaedic Hospital

London
HA7 4LP
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

01/02/2016: This trial was abandoned in 2012 due to lack of recruitment.