Macrophage Therapy for Acute Liver Injury (MAIL) Trial
Research type
Research Study
Full title
Macrophage Therapy For Acute Liver Injury (MAIL) Trial: A Phase 1 Randomised, Open-Label, Dose-Escalation Study to Evaluate Safety, Tolerability, and Activity of Allogeneic Alternatively Activated Macrophages (AAM) in Patients with Paracetamol-induced Acute Liver Injury.
IRAS ID
1005258
Contact name
James Dear
Contact email
Sponsor organisation
University of Edinburgh
Eudract number
2022-002584-29
ISRCTN Number
ISRCTN12637839
Research summary
This trial tests a new cell therapy for liver injury. Healthy people with no liver disease can develop sudden acute liver injury (ALI) which can lead to a syndrome called acute liver failure (ALF). ALF is characterised by bleeding, excessive pressure in the brain, kidney failure, and infection. ALF has no effective treatment other than liver transplantation, which has limited use because of its linked complications, expense to the health provider and scarcity of donor livers. Medicines are the most common cause of ALF in the Western world, especially paracetamol when taken in overdose. The only treatment for paracetamol overdose is called acetylcysteine, which prevents ALF only if treatment is started within around 8 hours of taking the tablets. For other causes of ALF there are currently no specific treatments.
Our new treatment is an infusion of cells called macrophages, which are large white blood cells that clear away damaged liver cells, reduce inflammation, and promote the regeneration of healthy liver tissue in mice with ALF. The macrophages will be made in the laboratory from cells called monocytes which are isolated from blood donated by healthy people.
This trial is the first-time macrophage therapy has been given to patients with ALI, but it builds on local expertise in similar clinical trials. The patients eligible to take part in this trial are those with ALI due to paracetamol overdose. The primary objective is to determine whether macrophage treatment is safe. The secondary objective is to determine whether there is any evidence that this treatment may improve the health of the injured liver. Patients will be included in cohorts with increasing doses. A group of independent experts will review the safety of each dose and decide whether or not the study can continue to the next higher dose. This study paves the way for a large trial of macrophage therapy for this condition and the development of macrophage therapy for other causes of ALF.REC name
North East - York Research Ethics Committee
REC reference
23/NE/0019
Date of REC Opinion
9 Mar 2023
REC opinion
Further Information Favourable Opinion