Trial registered on ANZCTR


Trial ID
ACTRN12610000985088
Ethics application status
Approved
Date submitted
26/10/2010
Date registered
15/11/2010
Date last updated
2/06/2011
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase 1 study to evaluate the potential role of mesenchymal stem cells in the treatment of chronic refractory tendinopathy
Scientific title
A phase 1 study to evaluate the potential role of mesenchymal stem cells in the treatment of chronic refractory Achilles tendinopathy
Secondary ID [1] 252959 0
MMRI#MSC-Ten-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Refractory Tendinopathy 258488 0
Condition category
Condition code
Musculoskeletal 258656 258656 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each patient will receive a single intratendon injection of unrelated, HLA-mismatched, placenta derived mesenchymal stem cells. There are 3 dosing arms in this study: low dose = 1x10^6, medium dose = 4 x10^6 and high dose = 16 x10^6 cells.
Intervention code [1] 257486 0
Treatment: Other
Comparator / control treatment
Nil
Control group
Dose comparison

Outcomes
Primary outcome [1] 259507 0
The primary objective of this study is to establish the feasibility and safety of precision local injections of allogeneic MSCs, from unrelated donors, in the treatment of chronic refractory degenerative Achilles tendonopathy.

This will be assessed by no evidence of acute toxicity within the first four hours following injection, adverse events, VISA score assessments and ultrasound assessment of the tendon
Timepoint [1] 259507 0
2 weeks, 4 weeks, 10 weeks and 26 weeks
Secondary outcome [1] 266103 0
The secondary objective is to document changes in related signs, symptoms, function, and radiological parameters, following precision intratendonous injection of MSCs, over a six month evaluation period.

This wll be assessed be VISA-A score assessments and ultrasound assessment of the tendon
Timepoint [1] 266103 0
2 weeks, 4 weeks, 10 weeks and 26 weeks

Eligibility
Key inclusion criteria
1. Male or female from 40 to 75 years of age.

2. Clinical diagnosis of mid-substance Achilles tendonopathy based on clinical assessment, including painful arc sign and The London Hospital Test.

3. Symptoms of Achilles tendonopathy for at least 18 months.

4. Power Doppler Ultrasound confirmation of diagnosis of Achilles tendonopathy by independent specialist musculoskeletal radiologist. The tendonopathy must be maximal within the mid-portion of the tendon (2-7cm from insertion), and must not involve the tenoperiosteal (insertion) or musculo-tendonous junctions.

6. Victorian Institute of Sport Assessment Score (VISA-A Questionnaire) of less than or equal to 55.

7. Previous treatment for Achilles tendonopathy from an Australian Registered Specialist Medical Practitioner relevant to the condition - Orthopaedic Surgeon, Rheumatologist, Sports Physician or Rehabilitation Physician.

8. Completion of medical specialist prescribed, Achilles exercise program for at least 4 days per week for 8 weeks. After which, VISA-A score must still be less or equal to 55.

9. Competency to understand the information given in the Human Research and Ethics Committee (HREC) approved Achilles tendonopathy Participant Information Sheet, and must sign the consent form prior to the initiation of any study procedures.
Minimum age
40 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Insertional Achilles tendonopathy, or muscle-tendon junction tendonopathy, as defined by an ultrasound scan.

2. Persisting full thickness tendon defect (e.g. full thickness tear which would not provide tendon construct.)

3. Evidence of underlying inflammatory or rheumatological disorder.

4. Calcific tendonopathy, or other abnormal tissue within the mid-portion of the Achilles tendon. (Note ectopic calcification, at the Achilles tendon insertion on the calcaneus would not constitute an exclusion criteria).

5. Tendonopathy associated with or aggravated by the recent use of medication known to cause tendonopathy (e.g. Fluoroquinones)

6. Either Achilles surgery within previous 6 months, or persistence of non-dissolving surgical material (e.g. sutures visible on ultrasound).

7. Local injection of corticosteroid or potential growth factors (e.g. Autologous Blood or Platelet Rich Plasma) within previous 3 months of potential MSC injection.

8. Recent use of oral corticosteroids within 3 months of potential MSC injection.

9. Inability to perform, or poor compliance to undertake, an exercise rehabilitation program. This will include assessment for co-existing conditions (e.g. osteoarthritis of the knee/ankle).

10. Bilateral tendonopathy whereby the principal investigator believes disease on the contralateral side may affect ability to undertake rehabilitation exercise program.

11. Requirement to take oral anti-inflammatories (including Aspirin).

12. Use of anticoagulant medication (e.g. Warfarin).

13. History of malignancies within the past 5 years, with the exception of squamous or basal cell carcinoma of the skin or successfully treated in situ carcinoma of the cervix.

14. Female who is of child-bearing potential .

15. Known history of alcohol abuse within 1 year of enrolment.

16. Co-morbid condition or illness limiting life expectancy to < 1 year at time of screening.

17. Serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with treatment, assessment or compliance with the protocol.
18. Allergy to all available antiseptics or local anaesthetics.

19. Positive serology for any of the following: HIV1, HIV2, HTLV1, HTLV2, Hepatitis B, Hepatitis C, or Syphilis (VDRL).

20. Abnormal haematology and biochemistry profiles. Abnormal profiles will be defined with respect to the normal laboratory ranges. Any measurement up to and including 5% variation of the normal laboratory ranges will be repeated after 1 week. If the abnormality persists, then the subject will be referred to their treating General Practitioner. If both the GP and the PI determine that the abnormality is of no clinical significance, then the subject will be able to re-enter the trial. Any subject with a laboratory measurement above 5 % from the normal range will not be able to enter trial and will be referred to their GP

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
Other
Other design features
Different groups of participants receive different interventions at different times during the study.
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

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
Current
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 257934 0
Self funded/Unfunded
Name [1] 257934 0
Dr Mark Young
Address [1] 257934 0
C/O Aubigny Place
Raymond Terrace
South Brisbane
Qld 4101
Country [1] 257934 0
Australia
Primary sponsor type
Other
Name
MMRI
Address
Aubigny Place
Raymond Terrace
South Brisbane
Qld 4101
Country
Australia
Secondary sponsor category [1] 257125 0
None
Name [1] 257125 0
Address [1] 257125 0
Country [1] 257125 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259946 0
Mater Health Services
Ethics committee address [1] 259946 0
Level 3 Quarters Building
Mater Health Services
Raymond Terrace
South Brisbane QLD 4101
Ethics committee country [1] 259946 0
Australia
Date submitted for ethics approval [1] 259946 0
11/11/2010
Approval date [1] 259946 0
06/04/2011
Ethics approval number [1] 259946 0
1658A

Summary
Brief summary
The purpose of this study is to assess if mesenchymal stem cells are a safe and effective therapeutic treatment option for people suffering from chronic disabling tendinopathy, who have no other effective treatment options
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31834 0
Address 31834 0
Country 31834 0
Phone 31834 0
Fax 31834 0
Email 31834 0
Contact person for public queries
Name 15081 0
Dr Mark Young
Address 15081 0
C/O MMRI
Aubigny Place
Raymond terrace
South Brisbane Qld 4101
Country 15081 0
Australia
Phone 15081 0
+61 7 38311908
Fax 15081 0
Email 15081 0
myoung@mmri.mater.org.au
Contact person for scientific queries
Name 6009 0
Dr Mark Young
Address 6009 0
C/O MMRI
Aubigny Place
Raymond terrace
South Brisbane Qld 4101
Country 6009 0
Australia
Phone 6009 0
+61 7 38311908
Fax 6009 0
Email 6009 0
myoung@mmri.mater.org.au