Condition category
Musculoskeletal Diseases
Date applied
10/05/2011
Date assigned
16/09/2013
Last edited
27/08/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Osteoarthritis is a condition that affects the bone and cartilage (the protective surface that allows your joints to move smoothly). Symptoms include joint damage, pain and loss of mobility, and in the longer term most patients need a total joint replacement. Cell therapy is a novel method of treating patients with damaged cartilage and bone, but it is not yet known which type of cells would do this best. Patients with cartilage damage have been treated with cartilage cells (chondrocytes) for over 10 years and patients with bone fractures that fail to heal properly are treated with stem cells from their bone marrow. In all, over 400 patients to date have been treated with their own cells for cartilage and/or bone repair. These patients are treated with cells that have been grown in specialist facilities available on the hospital site from small samples of their own cartilage or bone marrow. Since this technique uses the patients' own cells (called autologous), the cells are not likely to cause an immune reaction. The aim of this study is to see whether stem cells from bone marrow will be able to repair the damage to joints better than cartilage cells, or if the two cell types are better when used in combination.

Who can participate?
Patients aged between 18 and 80 with osteoarthritis of the knee.

What does the study involve?
Participants will be randomly allocated to be treated with either stem cells from bone marrow, cartilage cells, or both cell types combined. All participants will be followed up for 20 years after treatment.

What are the possible benefits and risks of participating?
Not provided at time of registration.

Where is the study run from?
Robert Jones and Agnes Hunt Orthopaedic Hospital (UK).

When is study starting and how long is it expected to run for?
September 2011 to September 2035.

Who is funding the study?
Arthritis Research UK.

Who is the main contact?
Prof James Richardson
janet.morris@rjah.nhs.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof James Richardson

ORCID ID

Contact details

Institute of Orthopaedics
Robert Jones and Agnes Hunt Orthopaedic Hospital
Oswestry
SY10 7AG
United Kingdom
+44 (0)1691 404386
janet.morris@rjah.nhs.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

R5242 A789

Study information

Scientific title

Autologous cell therapy for osteoarthritis: an evaluation of the safety and efficacy of autologous transplantation of articular chondrocytes and/or bone marrow-derived stromal cells to repair chondral/osteochondral lesions of the knee

Acronym

ASCOT

Study hypothesis

The ASCOT trial will be testing the following three alternative hypotheses:
1. Using autologous bone marrow stromal cells (BMSCs to repair chondral or osteochondral defects in the knee gives a different functional outcome from using autologous chondrocytes.
2. Using a combination of autologous BMSCs and autologous chondrocytes to repair chondral or osteochondral cartilage defects in the knee gives a different outcome from using autologous chondrocytes alone.
3. Using a combination of autologous BMSCs and autologous chondrocytes to repair chondral or osteochondral cartilage defects in the knee gives a different outcome from using autologous BMSCs alone.

Ethics approval

1. NRES Committee West Midlands - Coventry & Warwickshire; 29/07/2011; Ref: 11/WM/0175
2. Substantial amendment (AM1 21/05/2013) approval date: 06/06/2013
3. Non-substantial amendment (AM2 19/06/2013) acknowledgement date: 16/09/2013

Study design

Single-centre single-blind three-arm randomised controlled trial with long-term follow-up

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Symptomatic cartilage defects in the knee

Intervention

According to the treatment allocation, trial participants will receive one of the three following cell therapy strategies:
1. Autologous chondrocytes:
1.1. One syringe containing resuspended autologous chondrocytes will be supplied, containing between 1 and 20 million cells depending on the cell kinetics of the individual patient
1.2. It is recommended that the full dose is used
2. Bone marrow-derived stromal cells (BMSCs):
2.1. One syringe containing resuspended autologous BMSCs will be supplied, containing between 1 and 20 million cells depending on the cell kinetics of the individual patient
2.2. It is recommended that the full dose is used
3. Autologous chondrocytes and BMSCs combined:
3.1. Two syringes will be supplied, one containing resuspended autologous chondrocytes and one containing resuspended BMSCs, each containing between 1 and 20 million cells, depending on the cell kinetics of the individual patient
3.2. It is recommended that half of each syringe will be used
3.3. Therefore the patient will receive a total cell population of between 1 and 20 million cells
3.4. This will prevent a bias of one group in the study having generally twice the number of cells in the other two groups
4. Each of the three groups will receive the intervention in two stages:
4.1. Cell harvesting stage
4.2. Cell implantation stage
5. There is approximately 3 weeks between the two stages
6. All participants will be followed up for 20 years after the second stage of treatment is complete

Intervention type

Biological/Vaccine

Phase

Drug names

Primary outcome measures

Patient-reported functional knee score (Modified Lysholm) at 15 months, taking into account the pre-operative score as a covariate

Secondary outcome measures

1. Incidence of adverse events
2. Quality of the repair tissue determined using the Oswestry Arthroscopy Score, for which participants will undergo a repeat arthroscopy between 12 and 15 months
3. A 2mm diameter needle biopsy will also be taken at this time, and the histology analysed by a blinded assessor using the International Cartilage Repair Society (ICRS) II histology scoring system
4. An MRI/CT scan will also be performed, with the participants' agreement, and scored by a blinded assessor using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) Score
5. Health related quality of life, pain, knee function, activity levels and general mood of the patient will be assessed at 2m, 12m, 15m and annually up to 20 years post treatment using the following scores respectively:
5.1. The Veterans Rand 12 Item Health Survey (VR-12)
5.2. the Intermittent and Constant Osteoarthritis Pain score (ICOAP)
5.3. KOOS physical function short form (KOOS-PS)
5.4. Modified Lysholm Score
5.5. Human Activity Profile (HAP)
5.6. International Positive and Negative Affect Schedule Short Form (I-PANAS-SF)
6. Number of years free from further surgery
7. Observed patterns of rehabilitation and compliance to physiotherapy schedules will be collected using a participant diary up to 15 months post treatment
8. Unit costs per treatment will be recorded in order to perform a cost utility analysis

Overall trial start date

01/09/2011

Overall trial end date

01/09/2035

Reason abandoned

Eligibility

Participant inclusion criteria

1. A symptomatic defect of the knee that extends to (Outerbridge grade 4) or into the subchondral bone
2. The patient will be aged between 18 and 80 years at the time of surgery
3. The defect is considered suitable for ACI
4. Surgical treatment has been performed on the same defect at least 6 months previously and has failed to relieve symptoms
5. The patient is able to provide written informed consent to participate in the trial

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

111

Participant exclusion criteria

1. English is not the first language of the patient
2. Likely to show contraindications to autologous cell therapy:
2.1. Osteoarthritis
2.2. Inflammatory arthritis
2.3. Previous or current malignant tumour
2.4. Therapy with steroids or methotrexate
2.5. Bleeding tendency or known anaphylaxis to any product used in chondrocyte preparation
3. Low probability of compliance with physiotherapy or follow-up, including a major life threatening condition
4. A defect of greater than 20cm2 in total area
5. The patient is shown to be positive for serology tests required by the cell provider. This includes:
5.1. HIV
5.2. Hepatitis B and C
5.3. Syphilis
5.4. Human T cell lymphotrophic virus (HTLV) I & II
6. Pregnancy or lactation
7. Exclusion criteria (5) and (6) will not be confirmed until after written informed consent is obtained

Recruitment start date

01/09/2011

Recruitment end date

01/09/2035

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Robert Jones and Agnes Hunt Orthopaedic Hospital
Oswestry
SY10 7AG
United Kingdom

Sponsor information

Organisation

Robert Jones and Agnes Hunt Orthopaedic Hospital (UK)

Sponsor details

Arthritis Research Centre
Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust
Oswestry
SY10 7AG
United Kingdom
+44 (0)1691 404000
teresa.jones@rjah.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Arthritis Research UK ref: 18480

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes