Condition category
Digestive System
Date applied
29/06/2016
Date assigned
04/07/2016
Last edited
05/07/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Liver disease can overtime cause scarring and damage to the liver and eventually lead to a condition called liver cirrhosis. When this happens the liver is unable to work properly and the person can become tired and unwell. A malfunctioning liver makes people prone to infection, bruising, swelling, confusion and jaundice (yellowing of the skin). Cirrhosis is the fifth most common cause of death in UK. Currently we have no cure for liver cirrhosis but liver transplant. This is a very big operation which requires lifelong treatment with immunosuppressant drugs. Not everyone is suitable to have a liver transplant and there aren’t enough transplantable livers to cure all the patients. Our group has demonstrated using animals models that selected cells (monocytes) taken from the patient’s own blood can be grown in the laboratory into cells called macrophages and infused back into the patient to replace damaged liver cells. The aim of this study is to test the safety and effectiveness of autologous macrophage infusion in humans.

Who can participate?
Adults age 16-75 with liver cirrhosis

What does the study involve?
The first part of the study is to check that the macrophages are safe and find out the best number of macrophages to use. Three patients receive the same dose and if there are no side effects the dose is increased for the second group of three patients, until the maximum safe dose is reached. The second part of the study looks at whether the treatment can benefit patients with liver disease. Patients are randomly allocated to receive either the macrophage treatment or standard medical care. Liver function is then assessed after 3 months.

What are the possible benefits and risks of participating?
Patients may not gain direct benefit from the study but this could lead to the development in the future of a treatment for liver cirrhosis. This is a first in human study so the side effects are not known. We could potentially witness side effects similar to blood transfusion reactions or allergic reactions. Macrophages Activation Syndrome is a very rare condition that could potential arise from this treatment. This will be characterised by low blood pressure and difficulties in breathing. Appropriate measures are in place in the remote eventuality this may occur. Liver function could worsen. There is no information available to support the increased risk of cancer but it is difficult to predict. Patients could experience discomfort during blood sampling.

Where is the study run from?
Edinburgh Royal Infirmary (UK)

When is the study starting and how long is it expected to run for?
August 2016 to August 2021

Who is funding the study?
Medical Research Council (UK)

Who is the main contact?
Prof. Stuart Forbes
Stuart.Forbes@ed.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Francesca Moroni

ORCID ID

Contact details

SCRM Building
University of Edinburgh
5 Little France Drive
Edinburgh
EH164UU
United Kingdom
+44 (0)131 651 9510
fmoroni@ed.ac.uk

Additional identifiers

EudraCT number

2015-000963-15

ClinicalTrials.gov number

Protocol/serial number

MR/M007588/1

Study information

Scientific title

Macrophages therapy for liver cirrhosis

Acronym

MATCH01

Study hypothesis

Autologous macrophages therapy can improve liver function and reduce fibrosis in patients with established liver cirrhosis.

Ethics approval

REC - Research Ethics Committee South East Scotland, 24/06/2016, REC ref: 15/SS/0121

Study design

Dose-escalation phase I single-centre study with 3+3 design, followed by randomised controlled single-centre phase II study

Primary study design

Interventional

Secondary study design

Phase I safety and maximum tolerated dose study, phase II randomised controlled single centre study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, plase use contact details to request a partecipant informaton sheet

Condition

Liver cirrhosis

Intervention

Dose-escalation phase I single-centre study with 3+3 design: 3 patients will receive the same dose, if no dose-limiting toxicity recorded dose will be escalated to the second group of 3 patients until maximum tolerated dose.

Followed by randomised controlled single centre phase II study of autologous activated macrophage infusion versus standard medical care. Macrophages will be infused via peripheral vein for the duration of 30 minutes. Participants will be randomised 1:1 via computer system based on a minimisation algorithm using the key variable aetiology of disease. No blinding will be possible but efficacy data will be analysed at the end of the trail to avoid bias.

Intervention type

Biological/Vaccine

Phase

Drug names

Primary outcome measures

Phase I: The safety and feasibility of re-infusion of autologous macrophages, measured 14 days after infusion of 3rd patient in each dose escalation group (model 3+3), and the maximum safe dose of infusion
Phase II: Liver function (MELD score) at 3 months

Secondary outcome measures

1. Markers of liver fibrosis
2. Disease-related quality of life
3. Liver-related clinical events
4. Transplant-free survival
Measured at 3 months and 1 year (improvement in markers of fibrosis of the liver, improvement of quality of life, transplant free)

Overall trial start date

01/08/2016

Overall trial end date

01/08/2021

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age 17-65
2. Liver cirrhosis
3. Model for End-Stage Liver Disease (MELD) score 10-16
4. Aetiology liver disease: ALRD, NAFLD, PBC, hemochromatosis, alpha 1 anti trypsin deficiency, previous Hep C with SVR

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

65-74

Participant exclusion criteria

1. Refusal or inability to give informed consent to participate in the study
2. Other cause of chronic liver disease/cirrhosis not included in listed aetiologies – this is left to the clinical judgement of the investigator based on previous investigations and trial screening
3. Portal hypertensive bleeding; active episode of bleeding requiring hospitalisation in the last 3 months where varices have not been eradicated by banding
4. Ascites unless, in the opinion of the investigator, the ascites is minimal and well controlled with no increase to diuretic therapy in last 3 months
5. Encephalopathy; current or requiring hospitalisation for treatment in last 3 months
6. Hepatocellular carcinoma – uncertain cases to be discussed at local hepatobiliary multidisciplinary meeting, dysplastic or indeterminate nodules to be excluded, regenerative or other nodules to be included at discretion of MDM
7. Previous diagnosis of hepatocellular carcinoma
8. Previous organ transplant or previous recipient of tissue
9. Listed for liver transplantation
10. Any situation that in the Investigators' opinion may interfere with optimal study participation such as alcohol or drug abuse, domicile too distant from study site, potential non-compliance or inability to co-operate
11. Presence of clinically relevant acute illness that in the opinion of the investigator might compromise the participant’s safe participation in the study
12. Presence or history of cancer within past 5 years with exception of adequately treated localised skin carcinoma, in situ cervical cancer or solid malignancy surgically excised in total without recurrence for 5 years
13. Pregnancy or breastfeeding

Recruitment start date

01/08/2016

Recruitment end date

01/08/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Edinburgh Royal Infirmary
Little France Crescent
Edinburgh
EH16 4SA
United Kingdom

Sponsor information

Organisation

ACCORD (UK)

Sponsor details

Research Governance & QA Office
Queens Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4T
United Kingdom
+44 (0)131 242 9418
fiach.o'mahony@ed.ac.uk

Sponsor type

University/education

Website

http://accord.scot/

Funders

Funder type

Research council

Funder name

Medical Research Council

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

05/07/2016: Internal review