Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000258550
Ethics application status
Approved
Date submitted
14/01/2015
Date registered
19/03/2015
Date last updated
6/06/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Evaluation of mesenchymal stem cells in the treatment of knee osteoarthritis – prospective case series data collection
Scientific title
The evaluation of autologous adipose derived mesenchymal stem cells as treatment for symptomatic knee osteoarthritis on pain, function and cartilage volume in osteoarthritis patients.
Secondary ID [1] 285974 0
Nil
Universal Trial Number (UTN)
U1111-1166-1062
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoarthritis 293916 0
Condition category
Condition code
Musculoskeletal 294217 294217 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will look to prospectively assess the response of symptomatic knee osteoarthritis to mesenchymal stem cell therapy using the following protocol :
- Intra-articular injection of 100million stem cells at 0 and 6 months (total of 200million cells).

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] 290953 0
Treatment: Other
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294008 0
Knee 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] 294008 0
Assessed at 0,1,3,6 and 12months post commencement of study.
Primary outcome [2] 294010 0
0-10 Numerical Pain Rating Scale (NPRS) - The NPRS has been validated for use in people with hip osteoarthritis
Timepoint [2] 294010 0
Assessed at 0,1,3,6 and 12months post commencement of study.
Primary outcome [3] 294011 0
MRI quantitative data including mapping of cartilage volume.
Timepoint [3] 294011 0
Assessed at commencement of study and again at 12months.
Secondary outcome [1] 312347 0
Global perceived effect scale. Measures of global effect are a recommended outcome measure for clinical trials
Timepoint [1] 312347 0
Assessed at 1,3,6 and 12months post commencement of study.
Secondary outcome [2] 312348 0
Pain Treatment Satisfaction Scale - a validated questionnaire
Timepoint [2] 312348 0
Assessed at 1,3,6 and 12months post commencement of study.
Secondary outcome [3] 312350 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] 312350 0
Assessed at commencement of study

Eligibility
Key inclusion criteria
Inclusion Criteria :
1. Radiological diagnosis of knee osteoarthritis using the American College of Rheumatology criteria (Altman, 1986).
2. Primary OA 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 dietitian 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 OA (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
Sex
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 knee symptoms suspected to be due to serious pathology such as tumour or referral from the hip or lumbar spine. These conditions are not under investigation within the current project.
5. Blood disorder (accepted contra-indication as no safety data on this population)
6. Anti-coagulant therapy that cannot safely be ceased.
7. History of cancer.

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. Google ads will also be used to gather attention within the general community.

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 KOOS, 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 KOOS 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 insufficient data published to date on the effects of autologous MSC on knee osteoarthritis. As such sample size calculations are not possible. We will aim to recruit 100 participants.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Adequate participant recruitment for case series analysis.
Date of first participant enrolment
Anticipated
27/11/2014
Actual
27/11/2014
Date of last participant enrolment
Anticipated
Actual
1/01/2017
Date of last data collection
Anticipated
Actual
1/03/2018
Sample size
Target
100
Accrual to date
Final
50
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 9115 0
3128 - Box Hill

Funding & Sponsors
Funding source category [1] 290565 0
Self funded/Unfunded
Name [1] 290565 0
Country [1] 290565 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] 289256 0
Commercial sector/Industry
Name [1] 289256 0
Melbourne Stem Cell Centre
Address [1] 289256 0
Level 2, 116-118 Thames St
Box Hill Nth 3128
Victoria
Country [1] 289256 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292206 0
Monash University Humam Research Ethics Committee
Ethics committee address [1] 292206 0
Ethics committee country [1] 292206 0
Australia
Date submitted for ethics approval [1] 292206 0
Approval date [1] 292206 0
03/11/2014
Ethics approval number [1] 292206 0
CF14/2230 - 2014001175

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 278 278 0 0
/AnzctrAttachments/367750-knee case series explanatory statement.pdf

Contacts
Principal investigator
Name 54058 0
Prof Richard Boyd
Address 54058 0
Department of Anatomy and Developmental Biology, School of Biological Sciences Monash University Clayton, Victoria 3800 Australia
Country 54058 0
Australia
Phone 54058 0
+6139905 0630
Fax 54058 0
Email 54058 0
[email protected]
Contact person for public queries
Name 54059 0
Julien Freitag
Address 54059 0
Melbourne Stem Cell Centre Level 2, 116-118 Thames St Box Hill Nth Victoria 3128
Country 54059 0
Australia
Phone 54059 0
+61392708000
Fax 54059 0
Email 54059 0
[email protected]
Contact person for scientific queries
Name 54060 0
Richard Boyd
Address 54060 0
Department of Anatomy and Developmental Biology, School of Biological Sciences Monash University Clayton, Victoria 3800 Australia
Country 54060 0
Australia
Phone 54060 0
+6139905 0630
Fax 54060 0
Email 54060 0
[email protected]

No information has been provided regarding IPD availability


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
SourceTitleYear of PublicationDOI
EmbaseThe effect of autologous adipose derived mesenchymal stem cell therapy in the treatment of a large osteochondral defect of the knee following unsuccessful surgical intervention of osteochondritis dissecans - A case study.2017https://dx.doi.org/10.1186/s12891-017-1658-2
N.B. These documents automatically identified may not have been verified by the study sponsor.