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Trial registered on ANZCTR


Trial ID
ACTRN12617000638336
Ethics application status
Approved
Date submitted
22/03/2017
Date registered
2/05/2017
Date last updated
4/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The evaluation of mesenchymal stem cells in the treatment of arthritis
Scientific title
Evaluation of adipose derived mesenchymal stem cells for the treatment of arthritis
Secondary ID [1] 291513 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Arthritis 302602 0
Condition category
Condition code
Musculoskeletal 302123 302123 0 0
Osteoarthritis
Inflammatory and Immune System 302124 302124 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will look to prospectively assess the response of symptomatic joint arthritis to mesenchymal stem cell therapy using the following protocol :
- Intra-articular injection of up to 50million stem cells at 0 and 6 months.

This will be a single treatment group uncontrolled case series.

Autologous adipose derived mesenchymal stem cells will be used due to the ease of harvest (liposuction) and safety. A small abdominal liposuction will be performed by an appropriately qualified medical clinician. This will be a day procedure and will take up to 1 hour. Isolation and expansion of mesenchymal stem cells will be performed in a suitably certified clean room facility operated by Magellan Stem Cells.

Commencement of therapy will be performed no earlier than 8 weeks after liposuction due to time taken to isolate and expand the mesenchymal stem cells.

Intra-articular (joint) injections will be performed by a suitably qualified procedural clinician with an medical degree equivalent of Bachelor of Medicine & Bachelor of Surgery (MBBS). These injections will be performed under radiological guidance.

Dose of mesenchymal stem cells will be dependent on the size of joint treated (ie. Knee - 50Millions MSCs, hip/ankle/shoulder - 20Millions MSCs, small joints of the hand - 10Million MSCs)

Only one joint/region will be treated at any given time.

The repeat injection at 6months will use mesenchymal stem cells previously isolated, expanded and stored from the initial harvest procedure. Mesenchymal stem cell will be cryopreserved in clinical grade qualified MSC cryoprotectant media using a validated control rate freezing method and stored in liquid nitrogen until use.
Intervention code [1] 297588 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 301558 0
Joint Pain : assessed using the Numeric Pain Rating Scale
Timepoint [1] 301558 0
Assessment at 0,1,3,6,9 and 12monts post commencement of therapy
Primary outcome [2] 301709 0
Pain and functional outcome : using a validated joint specific outcome score (i.e Knee injury and Osteoarthritis Outcome Score - KOOS, Hip injury and Osteoarthritis Outcome Score - HOOS)
Timepoint [2] 301709 0
Assessment at 0,1,3,6,9 and 12months post commencement of therapy
Secondary outcome [1] 333022 0
MRI assessment of cartilage volume.
Timepoint [1] 333022 0
Assessed at commencement of study and again at 12months
Secondary outcome [2] 333641 0
MRI assessment of cartilage quality using T2mapping techniques
Timepoint [2] 333641 0
Assessed at commencement study and again at 12months

Eligibility
Key inclusion criteria
Inclusion Criteria :
1. Radiological diagnosis of arthritis using the American College of Rheumatology criteria (Altman, 1986).
2. Primary arthritis treatment already undertaken defined as: analgesia/anti-inflammatory medication, supplements approved by the treating clinician (eg glucosamine sulphate), an attempted exercise program prescribed by a physiotherapist or medical practitioner for at least 8 weeks (Petrella, 2000), weight loss and nutritional management as prescribed by a dietician or medical practitioner for at least 8 weeks, and biomechanical management including bracing if appropriate as prescribed by a physiotherapist, podiatrist or medical practitioner. Autologous MSC is an invasive treatment and guidelines recommend trialling conservative measures as the first line of treatment in osteoarthritis (Thompson, Gordon et al. 2009).
3. Sufficient English skills to complete the questionnaires required for the study, as well as to understand the instructions given by the study doctors. This is required as no funding is available for translation or interpreters, and the outcome questionnaires to be used have only been validated in English language.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria:
1. Age <18yrs.
2. Pregnancy (accepted contra-indication as no safety data on this population).
3. Breastfeeding (accepted contra-indication as no safety data on this population).
4. Have other causes of their symptoms suspected to be due to serious pathology such as tumour or referral from the spine. These conditions are not under investigation within the current project.
5. Current cancer.
6. History of significant organ impairment/failure (ie. renal failure).
7. History of allergy to any substances used within the treatments.
8. Bovine allergy

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)
Efficacy
Statistical methods / analysis
Data analysis will focus on change in pain, function and quantitative MRI measures (with 95% confidence intervals) at each of the follow-up points (1-month, 3-months, 6-months and 12-months). Analyses will be conducted using SPSS Version 21, with alpha set at 0.05 using a two-tailed hypothesis. Continuous data will be analysed using linear mixed models. These were chosen for their strength in analysing longitudinal biological data and accounting for correlations associated with repeated measurement. The mixed models will adjust for the baseline score of the outcome of interest as recommended by the revised CONSORT statement. Ordinal data will be analysed using the Mann Whitney U test.
At each follow-up point, participants will be dichotomised according to whether they achieved the minimum clinically important difference of the outcome or not, and then the risk ratio, risk difference and number needed to treat will be calculated along with 95% confidence intervals. Statistical significance will be evaluated using Chi square analysis.
All participants who withdraw from treatment for any reason will continue to be contacted for follow-up assessments and informed that their data are still required. Missing data will be handled via restricted maximum likelihood estimation within the linear mixed models. Given the popularity of simple data imputation methods we will undertake a secondary sensitivity analysis to determine whether the results would differ if missing data were replaced using the last observation carried forward method.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 296003 0
Self funded/Unfunded
Name [1] 296003 0
Participants in the study fund their own treatment.
Address [1] 296003 0
Country [1] 296003 0
Primary sponsor type
Commercial sector/Industry
Name
Melbourne Stem Cell Centre
Address
Level 2, 116-118 Thames St
Box Hill Nth 3128
Victoria
Country
Australia
Secondary sponsor category [1] 294890 0
Commercial sector/Industry
Name [1] 294890 0
Magellan Stem Cells
Address [1] 294890 0
Level 2, 116-118 Thames St
Box Hill Nth 3128
Victoria
Country [1] 294890 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297265 0
Charles Sturt University Human Research Ethics Committee
Ethics committee address [1] 297265 0
The Executive Officer
Human Research Ethics Committee
Charles Sturt University
Locked Bag 588
Wagga Wagga NSW 2678
Ethics committee country [1] 297265 0
Australia
Date submitted for ethics approval [1] 297265 0
01/11/2016
Approval date [1] 297265 0
07/12/2016
Ethics approval number [1] 297265 0
H16171

Summary
Brief summary
The purpose of this study is to formally follow up and record the effectiveness of autologous (your own) stem cell injections in the treatment of arthritis. A secondary objective is to determine whether stem cell therapy offers disease modifying potential and therefore whether it can limit, prevent or possibly reverse progression of arthritis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73510 0
Dr James Wickham
Address 73510 0
School of Biomedical Sciences
Charles Sturt University
Leeds Parade
Orange, NSW 2800
Country 73510 0
Australia
Phone 73510 0
+61 3 92708000
Fax 73510 0
Email 73510 0
info@mscc.com.au
Contact person for public queries
Name 73511 0
Dr James Wickham
Address 73511 0
School of Biomedical Sciences
Charles Sturt University
Leeds Parade
Orange, NSW 2800
Country 73511 0
Australia
Phone 73511 0
+61 3 92708000
Fax 73511 0
Email 73511 0
info@mscc.com.au
Contact person for scientific queries
Name 73512 0
A/Prof Julien Freitag
Address 73512 0
Melbourne Stem Cell Centre
116-118 Thames St
Box Hill North
Vic 3128
Country 73512 0
Australia
Phone 73512 0
+61 3 92708000
Fax 73512 0
Email 73512 0
info@mscc.com.au