Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12619000394145
Ethics application status
Approved
Date submitted
21/02/2019
Date registered
12/03/2019
Date last updated
3/12/2020
Date data sharing statement initially provided
12/03/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Skull repair using adult stem cells and a dissolving scaffold
Scientific title
Cranial Reconstruction Using Mesenchymal Stromal Cells and Resorbable Biomaterials in adults with a cranial defect.
Secondary ID [1] 297466 0
NCT01742260
Secondary ID [2] 297467 0
2012/022238
Secondary ID [3] 297468 0
2012/047
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Surgically-Created Resection Cavity 311660 0
Condition category
Condition code
Musculoskeletal 310281 310281 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is cranioplasty.

a) any physical or informational materials used,
Patient Information Sheets (PIS) will be provided to each patient enrolled in the trial.

b) each of the procedures, activities, and/or processes used,
1. Patient consent

2. Stem Cell Collection
• Blood Test
• Bone Marrow Aspirate
• MSC processing
• Delivery of Intervention by Haematologist

3. Insertion of cranioplasty

c) who will deliver the intervention,
Consultant Haematologist with regard to stem cells
Consultant Neurosurgeon with regard to cranioplasty insertion

d) the mode of delivery,
Face to face and in theatre

e) the number of times the intervention will be delivered and over what period of time,
Once at time of theatre.

f) the location/setting where the intervention occurs.
Major Public Hospital
Intervention code [1] 313720 0
Treatment: Surgery
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319174 0
Failure of cranioplasty implant - The primary outcome measures will be failure of the tissue engineered construct such that it requires removal ( for example due to infection, resorption, dislodgement or cosmetic failure), as well as any significant adverse events attributable to treatment allocation.

This is a composite outcome

Assessment
Infection: clinical assessment by Neurosurgeon
Resorption: CT scan at 12 most post op radiological assessment
Cosmesis: Assessment by Neurosurgeon at 3months, 6 months and 12months.
Position of plate: CT scan day Post op day 1
Timepoint [1] 319174 0
12 months
Secondary outcome [1] 367179 0
Quantitative bone density of the tissue engineered construct and adjacent bone from CT scan at 12 months.

Assessment: CT scan, analysis of Hounsfield units of host bone and of tissue engineered construct
Timepoint [1] 367179 0
12 months
Secondary outcome [2] 367180 0
Assessment of cosmesis by photography

Assessment: clinical photography at 3, 6 and 12 months.
Timepoint [2] 367180 0
12 months

Eligibility
Key inclusion criteria
- All adult patients (age > 18 years) who have a cranial defect that requires reconstruction with a defect size of less than 110 x 180mm.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients who have had a previous cranial infection

- Positive bone marrow aspirate on testing for microcontamination

- Positive testing for infectious disease

- Patients who have neurocognitive difficulties and are as such unable to provide
informed consent

- Patients with an ongoing intracranial infection following craniotomy

- Pregnant or breastfeeding females

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
6/02/2019
Date of last participant enrolment
Anticipated
6/02/2021
Actual
Date of last data collection
Anticipated
31/12/2022
Actual
Sample size
Target
20
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 13212 0
Royal Perth Hospital - Perth
Recruitment hospital [2] 13213 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [3] 13214 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 25769 0
6000 - Perth
Recruitment postcode(s) [2] 25770 0
6150 - Murdoch
Recruitment postcode(s) [3] 25771 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 302036 0
Government body
Name [1] 302036 0
WA State Health Research Advisory Council
Country [1] 302036 0
Australia
Primary sponsor type
Individual
Name
Stephen Honeybul
Address
Royal Perth Hospital
197 Wellington St Perth WA 6000
Country
Australia
Secondary sponsor category [1] 301845 0
None
Name [1] 301845 0
Address [1] 301845 0
Country [1] 301845 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302719 0
Royal Perth Hospital EC00270
Ethics committee address [1] 302719 0
Royal Perth Hospital
197 Wellington St Perth WA 6000
Ethics committee country [1] 302719 0
Australia
Date submitted for ethics approval [1] 302719 0
04/04/2012
Approval date [1] 302719 0
14/09/2012
Ethics approval number [1] 302719 0

Summary
Brief summary
Brief Summary
Cranial reconstruction using mesenchymal stromal cells and resorbable biomaterials, will result in the patient producing their own bone to fill the void which will reduce the risk of infection and resorption, lead to a better cosmetic result and obviate any long term consequence of having a synthetic material in vivo.
Introduction:

There are several reasons that parts of the skull may need to be removed:
- After trauma to relieve brain swelling
- During brain surgery (for brain cancer)
- After trauma where the bone is so badly fractured/fragmented it needs to be removed.

In all but the last case the bone flap is temporarily stored in a freezer and once the brain swelling has subsided it is reinserted. This procedure is called "autologous cranioplasty"; autologous, because it originally came from the patient and cranioplasty, referring to the repair. Although this is a straightforward procedure, there are a number of complications including infection and bone resorption that can occur.

This study:

Stromal cells have a proven ability to aid in bony healing. Furthermore stromal cells on a ceramic framework encased in a plastic scaffold have been shown in a small clinical trial to lead to healing of skull defects. In the present study, it is proposed to add stromal cells, either autologous or allogeneic, to a resorbable ceramic material and insert into the skull. The ceramic is designed to dissolve away over time as the body's own blood vessels and cells populate the construct and create the patient's new bone. It has been proven that without the encouragement of the cells and temporary scaffold materials, a hole in the skull will not heal. Given the incidence of bone resorption/infection and metal plate infection using traditional methods, it would seem prudent to provide a construct that will allow controlled replacement with the patient's own bone, thus negating any adverse long-term complications with synthetic materials that remain for life.
Trial website
Trial related presentations / publications
Public notes
The reason for listing the trial on ANZCTR is twofold. Firstly the person responsible for registering the trial in the US (clinicaltrials.org) retired and then could not login, and despite numerous attempts we were unsuccessful in gaining access . Secondly, we were advised by our ethics committee that it would be appropriate to register the trial with the ANZCTR,

Contacts
Principal investigator
Name 91150 0
Dr Stephen Honeybul, MD
Address 91150 0
Royal Perth Hospital
197 Wellington St, Perth WA 6000
Country 91150 0
Australia
Phone 91150 0
+61 892242500
Fax 91150 0
Email 91150 0
[email protected]
Contact person for public queries
Name 91151 0
A/Prof Alan Kop
Address 91151 0
Royal Perth Hospital
197 Wellington St, Perth WA 6000
Country 91151 0
Australia
Phone 91151 0
+61 892242500
Fax 91151 0
Email 91151 0
[email protected]
Contact person for scientific queries
Name 91152 0
A/Prof Alan Kop
Address 91152 0
Royal Perth Hospital
197 Wellington St, Perth WA 6000
Country 91152 0
Australia
Phone 91152 0
+61 892242500
Fax 91152 0
Email 91152 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Need to ensure participant privacy.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.