VIDA DTC: Systematic evidence-based approach to identifying and tailoring inflammation modulating treatments to improve clinical outcomes including cognition for patients with intracerebral haemorrhage

Background – 40% patients die in the first month after intracerebral haemorrhage (ICH) and of those who survive 30% will develop dementia with dementia risk linked to ICH severity and underlying small vessel disease including cerebral amyloid angiopathy.1 Finding an effective ICH treatment could improve outcomes including the risk of developing dementia after ICH. We have shown that brain swelling (peri-haematomal oedema) increases in the first two weeks after ICH and this tends to occur most in ICH in the lobes of the brain rather than ICH in other locations,2 which may be linked to cerebral amyloid angiopathy. Brain swelling is a biomarker of neuroinflammation and is associated with clinical outcome.3

Drug repurposing accelerates the identification of effective treatments and we have developed systematic evidence-based approaches to guide drug repurposing in clinical trials of MND.4 We will use similar approaches to identify potential inflammation modulating treatments for improving outcomes after ICH.

 Aim – To develop a framework to identify, evaluate, and prioritise repurposed inflammation-modulating drugs to improve clinical outcomes after ICH including reducing the risk of post-ICH cognitive impairment and dementia. We would aim to match information on potential candidate drugs with clinical features such as ICH location, to tailor drug selection to a given patient. We have a CSO funded feasibility study for an ICH platform trial – PLINTH nearmejobs.eu The University of Edinburgh and this will enable drug selection for a platform trial where a trial arm meeting predefined futility endpoints can be replaced with a new trial arm testing a different drug without interrupting study recruitment.

 Methods– We will create a systematic online living evidence summary of inflammation modulating drugs tested in human and animal models. We will integrate automated processes to continuously gather, synthesise and summarise all existing evidence from a research domain, and report the resulting content as interrogatable databases via interactive web applications. We will summarise the information for each drug and present the evidence to an expert panel for shortlisting.

 Patient and public involvement – We sought the opinion of ICH survivors on studying inflammation. 39 patients, carers, and members of the public responded to questions about the design. 87% strongly agreed that, “studying inflammation after brain haemorrhage is a priority.” We presented an outline of the proposed research to members of our patient group Patient Reference Group nearmejobs.eu Centre for Clinical Brain Sciences (ed.ac.uk). They supported it because they thought it was a good way of finding a treatment which improves outcomes for people with ICH.

VIDA (Vascular and Immune contributors to DementiA) is a new multi-institutional partnership between Alzheimer’s Society and four world-leading research sites: the University of Manchester, University of Edinburgh, Imperial, and City St George’s University of London. With projects focussing on the importance of vascular and immune mechanisms in dementia, VIDA PhD students will become the next generation of much-needed dementia researchers, contributing to breakthroughs in dementia diagnosis and treatment.

VIDA students will embark upon a 4 year fully-funded PhD project at one of the four institutions above, with access to the state-of-the-art research facilities and interdisciplinary training available at all sites. Students at each site will come together as a cohort at several points during the programme, most importantly for an induction week at the beginning of the programme, followed by annual conferences and residential workshop retreats which will link in with other Alzheimer’s Society Doctoral Training Centres across the UK. Students will also participate in engagement schemes with the Alzheimer’s Society and beyond, sharing the impact of their research in the community. The programme also benefits from built in opportunities for placements with leading industrial partners, and bespoke training plans including schemes to develop teaching, mentoring, and grant writing skills.

https://www.dementiaresearcher.nihr.ac.uk/vascular-and-immune-contributors-to-dementia/

https://www.alzheimers.org.uk/research/our-research/alzheimers-society-doctoral-training-centres/vascular-and-immune-contributors-dementia

Please apply using the INSTITUTION link which will take you to the APPLY HERE button to access detailed instructions and the EdNeuro.PhD APPLICATION FORM.