Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000636358
Ethics application status
Approved
Date submitted
22/03/2017
Date registered
2/05/2017
Date last updated
30/06/2021
Date data sharing statement initially provided
30/06/2021
Date results information initially provided
30/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of mesenchymal stem cells for the treatment of lower back pain
Scientific title
Evaluation of adipose-derived mesenchymal stem cells for the treatment of chronic lower back discogenic pain - a prospective, case series pilot study
Secondary ID [1] 291517 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lower Back Pain 302604 0
Condition category
Condition code
Musculoskeletal 302126 302126 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will look to prospectively assess the response of discogenic lower back pain to mesenchymal stem cell therapy using the following protocol :
- Intra-discal injection of 10million stem cells at commencement of treatment and a further injection at 6months if clinically indicated (i.e. persistent pain).

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. The 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 suitable 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-discal injections will be performed by a suitably qualified procedural clinician with a medical degree equivalent of Bachelor of Medicine & Bachelor of Surgery (MBBS). These injections will be performed under radiological guidance. The chosen disc for treatment will be determined by MRI analysis.

A decision to undergo a second injection at 6months will be determined after a clinical assessment by a study doctor at 6months.

Any repeat injections 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] 297590 0
Treatment: Other
Comparator / control treatment
Nil control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 301560 0
Lower Back Pain : assessed using a Numeric Pain Rating Scale
Timepoint [1] 301560 0
Follow-up will be conducted at baseline, 1, 3, 6, 9, 12 and 24 months.
- trial was extended to 24 months of follow-up with HREC approval after all participants were recruited.
Primary outcome [2] 301708 0
Safety and Tolerability of Treatment : assessed using an Adverse Event Registry
Previous studies using mesenchymal stem cells have noted an initial flare up in pain. Other studies using intra-venous administration of mesenchymal stem cells have observed a self limiting fever.
Timepoint [2] 301708 0
Adverse events documented at 1 week, 1 month, 3month, 6month, 9month and 12month time points.
Secondary outcome [1] 333024 0
Disc Structural Changes - assessed by MRI
Timepoint [1] 333024 0
MRI will be conducted prior to commencement of therapy and again at 12months post therapy.

Eligibility
Key inclusion criteria
1) 18 years or older
2) Severe low back pain
3) Failure with 3 months of conservative back pain care.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Age <18yrs
2. Breastfeeding (accepted contra-indication as no safety data on this population).
3. Blood disorder (accepted contra-indication as no safety data on this population)
4. Anti-coagulant therapy that cannot safely be ceased.
5. History of malignancy within 10years.

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
Completed
Date of first participant enrolment
Anticipated
31/05/2017
Actual
13/06/2017
Date of last participant enrolment
Anticipated
Actual
13/06/2018
Date of last data collection
Anticipated
Actual
8/10/2020
Sample size
Target
10
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 296006 0
Commercial sector/Industry
Name [1] 296006 0
Magellan Stem Cells
Country [1] 296006 0
Australia
Funding source category [2] 296007 0
Commercial sector/Industry
Name [2] 296007 0
Melbourne Stem Cell Centre
Country [2] 296007 0
Australia
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] 294893 0
Commercial sector/Industry
Name [1] 294893 0
MetroPain Group
Address [1] 294893 0
Ground Floor
Monash House
271 Clayton Rd
Clayton
Victoria, Australia
Country [1] 294893 0
Australia
Secondary sponsor category [2] 295051 0
Commercial sector/Industry
Name [2] 295051 0
Melbourne Stem Cell Centre
Address [2] 295051 0
Level 2, 116-118 Thames St
Box Hill Nth 3128
Victoria
Country [2] 295051 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297268 0
Charles Sturt University Human Research Ethics Committee
Ethics committee address [1] 297268 0
Research Office
Charles Sturt University
Locked Bag 588
Wagga Wagga NSW 2678
Ethics committee country [1] 297268 0
Australia
Date submitted for ethics approval [1] 297268 0
01/12/2016
Approval date [1] 297268 0
09/03/2017
Ethics approval number [1] 297268 0
H17027

Summary
Brief summary
Low back pain (LBP) is a major health problem affecting approximately 60-80% of the adult population at some stage. LBP is the second most common reason for physician visits, and for work disability and is associated with substantial health care costs.

The intervertebral disc (IVD) is the most common source of LBP, being the prime source in about 40% of complex chronic LBP presentations. Non-invasive options, such as pharmacological manipulation, exercise, physical therapy and pain management programs have limited evidence. Further, surgical interventions such as discectomy and fusion for disc
degeneration have similarly limited success. Cell based therapies may offer possibilities to
regenerate the IVD, restore or improve its function, leading to clinical success.

Mesenchymal stem cells (MSCs) are a very attractive cell source for use in restoring the normal cellular constitution of the degenerated disc. A recent pre-clinical animal study showed that implantation of bone marrow derived MSCs to degenerative discs inhibits fibrosis/scarring, preserving mechanical properties and overall spinal function. Furthermore, a study of 10 patients with confirmed disc related LBP and injected with autologous MSCs, described rapid improvement in pain and disability at 3 months, followed by a modest improvement within 6 and 12 months after injection.

Importantly, based upon current clinical trial outcomes, MSC therapy is low-risk. A recent
meta-analysis of trials involving a total of 1012 participants receiving MSC therapy for various
conditions , did not identify any significant adverse events other than transient fever.

The primary aim of this prospective case series pilot study is to evaluate the safety, tolerability
and dose efficacy of autologous mesenchymal stem cells in the treatment of internal disc
disruption (IDD) resulting in LBP. A secondary aim is to determine whether MSC therapy
offers disease modifying potential through the examination of structural changes using MRI.
Follow-up will be conducted over 12-months.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73522 0
Dr James Wickham
Address 73522 0
Charles Sturt University
School of Biomedical Sciences
Leeds Parade
Orange, NSW 2800
Australia
Country 73522 0
Australia
Phone 73522 0
+61 3 92708000
Fax 73522 0
Email 73522 0
[email protected]
Contact person for public queries
Name 73523 0
Ms Lera O'Connor
Address 73523 0
Ground Floor
Monash House
271 Clayton Rd
Clayton
Victoria
3168
Country 73523 0
Australia
Phone 73523 0
+61 3 95956111
Fax 73523 0
+613 9595 6182
Email 73523 0
[email protected]
Contact person for scientific queries
Name 73524 0
Dr David Vivian
Address 73524 0
Ground Floor
Monash House
271 Clayton Rd
Clayton
Victoria
3168
Country 73524 0
Australia
Phone 73524 0
+61 3 95956111
Fax 73524 0
Email 73524 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual de-identified participant data which underlie results reported in this article will be available upon publication. The study protocol will also be available. Material will be accessible to investigators whose proposed use of data has been approved by an independent review committee and for data meta-analysis. Requests are to be directed to the corresponding author of the article upon publication
When will data be available (start and end dates)?
Individual de-identified participant data which underlie results reported in this article will be available upon publication. The study protocol will also be available. Material will be accessible to investigators whose proposed use of data has been approved by an independent review committee and for data meta-analysis. Requests are to be directed to the corresponding author of the article upon publication. No end date determined for request of data.
Available to whom?
Individual de-identified participant data which underlie results reported in this article will be available upon publication. The study protocol will also be available. Material will be accessible to investigators whose proposed use of data has been approved by an independent review committee and for data meta-analysis. Requests are to be directed to the corresponding author of the article upon publication.
Available for what types of analyses?
Individual de-identified participant data which underlie results reported in this article will be available upon publication. The study protocol will also be available. Material will be accessible to investigators whose proposed use of data has been approved by an independent review committee and for data meta-analysis. Requests are to be directed to the corresponding author of the article upon publication.
How or where can data be obtained?
Individual de-identified participant data which underlie results reported in this article will be available upon publication. The study protocol will also be available. Material will be accessible to investigators whose proposed use of data has been approved by an independent review committee and for data meta-analysis. Requests are to be directed to the corresponding author of the article upon publication via email ([email protected])


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.