Trial registered on ANZCTR


Trial ID
ACTRN12615000257561
Ethics application status
Not yet submitted
Date submitted
15/01/2015
Date registered
19/03/2015
Date last updated
24/03/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of mesenchymal stem cells in the treatment of hip cartilage lesions post arthroscopic microfracture – prospective case series data collection
Scientific title
The evaluation of autologous adipose derived mesenchymal stem cells in combination with arthroscopic microfracture as treatment for symptomatic hip osteoarthritis on pain, function and cartilage volume in osteoarthritis patients.
Secondary ID [1] 285977 0
Nil
Universal Trial Number (UTN)
U1111-1166-1217
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoarthritis 293919 0
Condition category
Condition code
Musculoskeletal 294220 294220 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will look to prospectively assess the response of symptomatic hip full thickness cartilage lesions to arthroscopic microfracture combined with post operative mesenchymal stem cell therapy.

Arthroscopic microfracture is an accepted technique to treat areas of full thickness cartilage loss and encourage scar cartilage formation. This is performed as a day procedure within an orthopaedic hospital.

2 intra-articular hip joint injections of 100 × 10*6 autologous MSC will occur at 0 and 6months. Subjects will receive a total of 200 × 10*6 MSCs. The initial injection will be performed between 1-4weeks post arthroscopy and this timing will be determined by the treating physician.

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.
Intervention code [1] 290955 0
Treatment: Other
Intervention code [2] 291159 0
Treatment: Surgery
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294014 0
Hip Injury and Osteoarthritis Outcome Score -
consists of 5 subscales being pain, other symptoms, function in daily living, function in sport and recreation and knee related quality of life. It is reliable and valid for the population of people with osteoarthritis.
Timepoint [1] 294014 0
Assessed at 0,1,3,6 and 12months post commencement of study.
Primary outcome [2] 294018 0
0-10 Numerical Pain Rating Scale (NPRS) - The NPRS has been validated for use in people with hip osteoarthritis
Timepoint [2] 294018 0
Assessed at 0,1,3,6 and 12months post commencement of study.
Primary outcome [3] 294027 0
MRI quantitative data including mapping of cartilage volume.
Timepoint [3] 294027 0
Assessed at commencement of study and again at 12months.
Secondary outcome [1] 312354 0
Global perceived effect scale. Measures of global effect are a recommended outcome measure for clinical trials
Timepoint [1] 312354 0
Assessed at 1,3,6 and 12months post commencement of study.
Secondary outcome [2] 312357 0
Pain Treatment Satisfaction Scale - a validated questionnaire
Timepoint [2] 312357 0
Assessed at 1,3,6 and 12months post commencement of study.
Secondary outcome [3] 312362 0
The Orebro Musculoskeletal Pain Questionnaire will also be completed. This questionnaire has been to shown to be reliable and valid for detecting individuals at risk of developing persistent pain. This questionnaire will be used in the current study to assess the potential impact of psychosocial factors on participants’ outcome.
Timepoint [3] 312362 0
Assessed at commencement of study

Eligibility
Key inclusion criteria
Inclusion Criteria :
1. Radiological diagnosis of a hip cartilage lesion.

2. Primary 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 (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. OA does not commonly occur in people under 18.
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 ankle symptoms suspected to be due to serious pathology such as tumour or referral from the lumbar 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)
The trial will be advertised to both allied health and medical groups.

After direct enquiry from a possible participant and after an initial phone based screen, participants will be invited to attend for a formal assessment to ascertain their suitability for treatment and involvement in this prospective case series. If suitable they will be invited to enrol in the study and then complete a formal informed consent.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Case Series
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/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. For these purposes, the minimum clinically important difference will be defined as 10/100 for the HOOS, 2/10 for the NRS pain scales, at least “much improved” on the global rating of change scale and “very satisfied” on the treatment satisfaction scales. It has been argued that these values for minimum clinically important difference may be too low in some contexts, hence we will repeat this analysis using a threshold of 50% reduction in HOOS scores and NRS pain scores based on empirical validation studies suggesting that this may be a more suitable threshold for important differences.
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.

There is no data published to date on the effects of autologous MSC on hip cartilage defects. As such sample size calculations are not possible.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Trial had been withdrawn prior to commencement due to change in treatment protocol.
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 9117 0
3128 - Box Hill

Funding & Sponsors
Funding source category [1] 290567 0
Self funded/Unfunded
Name [1] 290567 0
Address [1] 290567 0
Country [1] 290567 0
Primary sponsor type
Commercial sector/Industry
Name
Magellan Stem Cells
Address
Level 2, 116-118 Thames St
Box Hill Nth 3128
Victoria
Country
Australia
Secondary sponsor category [1] 289258 0
Commercial sector/Industry
Name [1] 289258 0
Melbourne Stem Cell Centre
Address [1] 289258 0
Level 2, 116-118 Thames St
Box Hill Nth 3128
Victoria
Country [1] 289258 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 292208 0
Monash University Humam Research Ethics Committee
Ethics committee address [1] 292208 0
Human Ethics
Monash Research Office
Monash University
Level 1, Building 3e, Clayton Campus
Wellington Rd
Clayton VIC 3800, Australia
Ethics committee country [1] 292208 0
Australia
Date submitted for ethics approval [1] 292208 0
02/02/2015
Approval date [1] 292208 0
Ethics approval number [1] 292208 0

Summary
Brief summary
Osteoarthritis is a major cause of pain and disability world wide. This study aims to explore the effectiveness of arthroscopic microfracture in combination autologous mesenchymal stem cell (MSC) injections in the treatment of full thickness cartilage lesions of the hip. This study involves the use of autologous MSC, autologous meaning that the cells are taken from and injected back into the same person. Based on previous animal studies and initial human patients, these MSCs are expected reduce pain and assist in bone and cartilage tissue repair, and improve cartilage quality post micro fracture - thus supporting their potential in the treatment of hip osteoarthritis.
Trial website
http://www.melbournestemcellcentre.com/research/
Trial related presentations / publications
Public notes
Attachments [1] 350 350 0 0
http://www.anzctr.org.au/AnzctrAttachments/367755-EXPLANATORY STATEMENT - hip microfracture case series.pdf

Contacts
Principal investigator
Name 54078 0
Prof Richard Boyd
Address 54078 0
Department of Anatomy and Developmental Biology, School of Biological Sciences Monash University Clayton, Victoria 3800 Australia
Country 54078 0
Australia
Phone 54078 0
+6139905 0630
Fax 54078 0
Email 54078 0
richard.boyd@monash.edu.au
Contact person for public queries
Name 54079 0
Dr Julien Freitag
Address 54079 0
Melbourne Stem Cell Centre Level 2, 116-118 Thames St Box Hill Nth Victoria 3128
Country 54079 0
Australia
Phone 54079 0
+61392708000
Fax 54079 0
Email 54079 0
julien.freitag@mscc.com.au
Contact person for scientific queries
Name 54080 0
Prof Richard Boyd
Address 54080 0
Department of Anatomy and Developmental Biology, School of Biological Sciences Monash University Clayton, Victoria 3800 Australia
Country 54080 0
Australia
Phone 54080 0
+6139905 0630
Fax 54080 0
Email 54080 0
richard.boyd@monash.edu.au