World Encephalitis Day: Enceph-IG Trial22 February 2021
World Encephalitis Day on February 22 is a global awareness day where individuals and families affected by encephalitis (inflammation of the brain) come together to shine a light on the condition. The Centre for Trials Research at Cardiff University is fully co-ordinating the Intravenous Immunoglobulin in Autoimmune Encephalitis in Adults-A Randomised Double-Blind Placebo-Controlled Trial (Enceph-IG Trial)
Autoimmune encephalitis is swelling in the brain caused by the immune system attacking in error. It can cause people to become confused, drowsy, act out of character, and have seizures. It is a rare condition effecting approximately 6,000 people a year in the UK, according to the Encephalitis Society, and even though there are a range of treatment options available to tackle both the causes and symptoms of encephalitis, there isn’t a specific targeted treatment. The Enceph-IG Trial is hoping to help change that.
Typically, patients receive steroids but some patients are given intravenous immunoglobulin (IVIG) because some clinicians think it may help speed up recovery. There have been very few clinical trials looking at recovery time and IVIG use in those with autoimmune encephalitis, so we don’t really know if it is effective at speeding up recovery. IVIG can be associated with significant side effects and is very expensive because it is developed from donated blood. The aim of the current trial is to evaluate how effective early treatment with IVIG is in speeding up recovery from autoimmune encephalitis.
We are looking to recruit 356 patients, from 50 hospitals across the UK. The trial will be double blind, this means neither the patients, their families, nor the clinicians treating them will know whether they received IVIG or not. This is to avoid accidentally biasing the results. Once patients are recruited and randomised they will receive steroids and IVIG, or steroids and a placebo (a product that looks identical but which does not contain the active ingredient) for 5 days. Patients will be asked to regularly report on their recovery, and they will be assessed by a clinician at 2 weeks, 3 months, and 12 months after they enter the trial.
We are still very early on in the trial set up phase but the impact of COVID on research has meant that we have had to rethink a lot of our standard procedures. A trial comprises of lots of documents, such as detailed protocols and patient information sheets, which are developed collaboratively with the multi-disciplinary team. It has been a challenge to work on all of these documents remotely. Many of the grant collaborators are clinicians and during COVID they have been very busy with their clinical work or were drafted to cover COVID related healthcare. It has been so important before each meeting to identify the key priorities so that we can maximise the time we have with the collaborators and keep the trial moving forward. Given the delays experienced, we have been able to progress and were able to submit our trial for ethical review recently. We will also be utilising more digital tools for data collection and for training site staff in trial activities in order to streamline processes for our clinical teams at sites. We are hoping to start opening our first group of NHS sites in the summer.
Trials in rare disease areas can be difficult to do, so it is very important that any trial actually meets the needs of the specific patient group. The Enceph-IG trial has strong links with the Encephalitis Society, the leading charity advocating for Encephalitis patients and their families in the UK, and their patient advocate group has provided input from the inception of the trial. During the grant development stage, patients and their families were consulted on what they thought the most meaningful outcome would be patients, data collection methods, and frequency of follow up visits. Currently, we have a patient and public representative from Encephalitis Society sitting on our trial management group, and others sitting on our trial steering group.
We are very early on in the life cycle of this trial, so we won’t see results for another 5 years but because this is a rare disease area we are hoping that this will be a landmark trial and improve patient treatment for those with encephalitis.
The trial is funded through the NIHR NIHR Efficacy and Mechanism Evaluation programme (NIHR17/60/67).
The Chief Investigator is Professor Tom Solomon, Chair of Neurology University of Liverpool, @RunningMadProf
Trial Collaborators: Dr Benedict Michael (University of Liverpool), Dr Simon Keller (University of Liverpool), Dr Michael Griffiths (University of Liverpool), Dr Perry Moore (Salford Royal NHS Foundation Trust), Prof Richard Pleass (Liverpool School of Hygiene and Tropical Medicine), Dr Ava Easton (Encephalitis Society), Associate Prof Sarosh Irani (University of Oxford), Dr David Gillespie (Centre for Trials Research), Dr Emma Thomas-Jones (Centre for Trials Research), Dr Sylviane Defres (The Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool), Dr Mark Ellul (University of Liverpool), Dr Michael Lunn (University College London Hospital NHS Foundation Trust), Dr Michael Zandi (University College London Hospital NHS Foundation Trust)
The trial is sponsored by the University of Liverpool and fully coordinated by the Centre for Trials Research, Cardiff University.
The Centre for Trials Research is a UKCRC-registered clinical trials unit. It is publicly-funded to enable applied research that informs policy in health and social care in Wales and the UK, and is currently running studies across Wales, the UK and internationally. The Centre is funded through Welsh government by Health and Care Research Wales, and Cancer Research UK.