Autologous Stem Cells in Achilles Tendinopathy (ASCAT)

This study is looking at a new treatment, using the patient's own stem cells (the repair cells of the body), to see whether this can help reduce pain and promote healing of the Achilles tendon, without side effects.

Study Overview

• Status: Unknown
• Conditions: Tendinopathy; Achilles Tendinitis; Achilles Degeneration; Achilles Tendinitis, Right Leg; Achilles Tendon Thickening; Achilles Tendinitis, Left Leg
• Intervention / Treatment: Biological: Autologous Mesenchymal Stem Cells

Detailed Description

Tendon disorders compromise pain free activity and often progress to chronic pain with a major impact on quality of life. More than 85,000 patients each year see their general practitioner (GP) with Achilles Tendinopathy (AT) which affects the lower leg in young and middle aged adults. The main treatment is physiotherapy, although surgery is eventually considered in 25-45%of patients, an intervention that requires several months of immobilisation and has unpredictable outcomes.

Other treatments include, shockwave therapy, Platelet Rich Plasma (PRP) (a blood injection of platelet rich plasma) and steroid injections, but other than physiotherapy non have been shown to be better than placebo. There is a need for improved nonsurgical treatments. There is an established treatment in horses that involves injection of the horses own stem cells into the tendon, which has been shown to be effective but has never been used in man. We wish to translate the technology to humans and propose a pilot phase II trial to establish the safety of stem cells implanted in diseased human tendon. We aim to study 10 patients with chronic mid substance achilles tendinopathy to assess safety as our primary outcome measure. In addition we capture clinical outcomes scores and ultrasound appearances. Other than the stem cell injection, all assessments will be non invasive. Participants will be otherwise healthy adults, aged 18-70 and recruited from routine outpatient clinics at the Royal National Orthopaedic Hospital, presenting with a painful heel, diagnosed by a specialist as Achilles tendinopathy, and having already undergone a minimum of 6 months of physiotherapy. Each participant will have 6 months follow up. This study will help inform a larger clinical trial in the future for which a further ethics application will be made.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Andy Goldberg; Phone Number: 0208 909 5825; Email: andy.goldberg@rnoh.nhs.uk

Study Locations

• United Kingdom
  • London, United Kingdom, HA74LP
    • Recruiting
    • Royal National Orthopaedic Hospital
    • Principal Investigator: Andrew Goldberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged ≥18 and ≤ 70 (both males and females)
• Participants with chronic midportion AT (as defined by pain in region of AT and tender swelling in mid portion of AT (no tenderness over bony attachment to heel) with symptoms for longer than 6 months who have failed conservative treatment (at least a full course of physiotherapy) and for whom surgery is being considered
• Able to provide written informed consent

Exclusion Criteria:

• Previous bony surgery (e.g. reconstructive pelvic osteotomy) at or in proximity to the bone marrow harvest site
• Pregnancy or lactation
• Current use of steroids, anti-tumour necrosis factor (TNF) drugs, methotrexate, or ciprofloxacin (or use within 4 weeks of assessment for eligibility)
• Positive for hepatitis B virus (HBV), Hepatitis C virus (HCV), Human Immunodeficiency Virus (HIV 1 and 2), syphilis and human t-cell leukaemia virus (HTLV)
• Previous AT surgery on the tendon to receive mesenchymal stem cell (MSC) implantation
• Inflammatory arthritis
• Known or suspected underlying haematological malignancy
• Other active malignancy in the past 3 years
• Bovine or antibiotic allergy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Autologous Mesenchymal Stem Cells	Biological: Autologous Mesenchymal Stem Cells; Other Names: Mesenchymal Stem Cells; Cell Therapy; Stem Cells; Stromal Cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary safety outcome will be the incidence rate of Serious Adverse Reaction (SAR).	The primary safety outcome is the incidence rate of SARs. This will be expressed as the proportion of participants experiencing a SAR at any time over the 24 week follow-up period. Primary outcomes will be assessed by adverse events reporting, clinical assessment and ultrasound.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of success	The secondary efficacy outcome measure is the incidence of success at 6 months, where success is defined as a reduction of 2 or more points on VAS of pain and an increase of VISA-A score greater than the Minimum Clinically Important Difference (MCID).	6 months
Conventional ultrasound changes from baseline		Baseline immediately before implantation and at weeks 6, 12 and 24
Ultrasound Tissue Characterisation (UTC) changes from baseline		Baseline immediately before implantation and at weeks 6, 12 and 24
Inter-observer reliability of UTC against conventional US		Baseline immediately before implantation and at weeks 6, 12 and 24

Collaborators and Investigators

• Sponsor: University College, London
• Investigators: Principal Investigator: Andrew Goldberg, MBBS MD FRCSI FRCS(Tr&Orth), Royal National Orthopaedic Hospital NHS Trust, UCL

Publications and helpful links

General Publications

• Smith RK, Korda M, Blunn GW, Goodship AE. Isolation and implantation of autologous equine mesenchymal stem cells from bone marrow into the superficial digital flexor tendon as a potential novel treatment. Equine Vet J. 2003 Jan;35(1):99-102. doi: 10.2746/042516403775467388. No abstract available.
• Goldberg AJ, Zaidi R, Brooking D, Kim L, Korda M, Masci L, Green R, O'Donnell P, Smith R. Autologous Stem Cells in Achilles Tendinopathy (ASCAT): protocol for a phase IIA, single-centre, proof-of-concept study. BMJ Open. 2018 May 14;8(5):e021600. doi: 10.1136/bmjopen-2018-021600.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (ANTICIPATED): December 1, 2018

Study Registration Dates

• First Submitted: February 12, 2014
• First Submitted That Met QC Criteria: February 13, 2014
• First Posted (ESTIMATE): February 17, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): May 12, 2016
• Last Update Submitted That Met QC Criteria: May 11, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Musculoskeletal; Achilles Tendinopathy; Autologous Stem Cells
• Additional Relevant MeSH Terms: Wounds and Injuries; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Tendon Injuries; Bone Diseases; Hyperostosis; Tendinopathy; Bursitis; Exostoses
• Other Study ID Numbers: 12/0419; 2013-000966-12 (EUDRACT_NUMBER)