NORMALISE, version 0.9
Research type
Research Study
Full title
Inhibition of PD-1 to Restore Monocyte/Macrophage Function in Liver Failure
IRAS ID
313128
Contact name
Mark Thursz
Contact email
Sponsor organisation
Imperial College London
Clinicaltrials.gov Identifier
2022-000402-94 , EudraCT number
Duration of Study in the UK
1 years, 6 months, 31 days
Research summary
Liver failure may occur in people with previously healthy livers (acute liver failure) or in patients with cirrhosis (acute decompensation). Irrespective of the cause, liver failure is a serious medical emergency which may progress to failure of other organs (including the kidneys, heart, lungs and brain) and death. Patients have increased risk of death due to susceptibility to infection. We have recently found one of the causes of reduced immune function in an animal model of liver failure. In the model immune cells resident in the liver, called macrophages, and their circulating counterparts, monocytes, are unable to clear bacteria from the blood. The bacteria are therefore able to disseminate throughout the body and cause infection. In the model we were able to reverse the immune defect using an anti-PD1 antibody which is currently used to treat some types of cancer. We have preliminary evidence that the same problem with macrophages and monocytes occurs in patients with liver failure. This programme of research sets out to investigate whether the anti-PD1 antibody is able to reverse the immune defect seen in patients with liver failure. To assess safety we will run two sentinel (safety) cohorts and monitor the patients carefully before progressing with the main study. To demonstrate that anti-PD1 antibody restores immune function we will carefully examine monocytes from blood before and after treatment. In addition to testing the immune response to anti-PD1 antibody we will investigate whether this treatment reduces the risk of infection. Patients with liver failure are always kept under close surveillance for infection so we will be able to measure whether the rate of infection is reduced by treatment compared to the rate of infection that we would expect.
REC name
London - Harrow Research Ethics Committee
REC reference
22/LO/0397
Date of REC Opinion
20 Jun 2022
REC opinion
Unfavourable Opinion