Scientific title:
Ischaemic lesions in acute intracerebral haemorrhage: pathophysiological investigation using novel multimodal cerebral and systemic haemodynamic assessments (CHALLENGE-ICH)
Institution:
University of Leicester
Principal investigator:
Dr Jatinder Minhas
Region:
Grant value:
£234,996
Research ID:
SA SCLM 23\100003
Research area:
Start date:
Thursday 1 February 2024
End date:
Wednesday 31 January 2029
Duration:
5 years
Status:
Active
Year awarded:
2023

Why is this research needed?

About one in every seven strokes is caused by bleeding deep inside the brain, known as an intracerebral haemorrhage or ICH.

Bleeding strokes like ICH are often caused by high blood pressure bursting a small blood vessel, leading to blood leaking into the brain and damaging nearby cells. Unfortunately, our bodies' response to injured cells is to bring blood to them to help them repair themselves - but in a bleeding stroke, this just causes more brain damage. This is one reason why strokes caused by bleeding are about twice as likely to be deadly as those caused by blood clots.

Clinical guidelines in the UK recommend treating ICH by intensively lowering blood pressure. There is also a less intensive blood pressure lowering treatment which can be used. Both help to bring the bleeding under control, but the intensive treatment does so more quickly.

Large clinical trials comparing the two treatments showed that the intensive treatment was potentially helpful for some patients, but that a "one size fits all" approach may not reduce the odds of death and disability for everyone who has an ICH.

Jatinder says, "Through caring for patients with bleeding strokes, I began to realise that whilst they are at risk of further bleeding strokes, the risk of clotting strokes is also high for them."

His theory, which he will test during his Senior Clinical Lectureship, is that intensive blood pressure lowering treatment might be causing these clots to form. Because we can't target blood pressure changes to the area where the bleed is happening, this treatment reduces blood flow to the whole brain. For some people, especially people whose blood vessels have narrowed because of low levels of carbon dioxide in their blood, this reduced flow could create blood clots even as it's treating the bleeding stroke.

What are the aims of this research?

Jatinder has already shown that injections of sodium bicarbonate, a readily available chemical that's already known to be safe for use in other conditions, can improve blood flow around the brain. However, he first needs to understand whether the increased risk of clotting strokes is actually caused by reduced blood flow in the brain.

In his previous research, Jatinder found out that carbon dioxide levels have effects on blood flow in the brain during a stroke. However, it is not yet clear whether low carbon dioxide levels and low brain blood flow could cause clotting strokes after ICH.

He will ask 120 ICH patients to have some extra assessments beyond the standard care that they receive. These will include measures of blood pressure and breathing rate, plus some extra brain scans to look for any new brain damage (caused by clotting strokes) that appears in the first week after the stroke. Finally, he’ll follow up with them three months after the stroke to find out how they're doing - for example, what kinds of disabilities do they have as a result of their stroke?

Together with his collaborators, Jatinder will look at the relationships between the different assessments. This will enable him to see whether changes to blood flow caused by intensive blood pressure lowering are causing more brain damage for some people. It will also reveal which groups of patients are most at risk of developing clots.

Finally, Jatinder and his team will use the information they've gathered to plan for a future clinical trial looking at whether sodium bicarbonate could reduce the risk of clotting strokes after ICH.

What is the benefit of this research?

Within five years, Jatinder's work should give us a much better understanding of the risks and benefits of intensive blood pressure lowering, improving clinical decision-making about ICH. For example, healthcare professionals will be able to provide patients with more personalised information about the risks and benefits of this treatment. However, at this point the only alternative treatment they might be able to offer is standard blood pressure lowering, which is not as effective for the immediate problem of slowing down bleeding.

In the longer term, Jatinder hopes that his research will mean ICH patients who need it can be given a sodium bicarbonate injection alongside intensive blood pressure lowering. This would be the best of both worlds for these high-risk patients: the most effective immediate treatment with protection against the long-term damage it could cause.

Jatinder says, "The opportunity to inform acute stroke management decisions through a non-invasive, inexpensive and bedside-based imaging modality will mean we can deliver improved clinical care with greater certainty that our treatments do not have harmful consequences for the brain's blood supply."

What PSP priorities does this research link to?

From 2019 to 2021, we worked with the James Lind Alliance on the Stroke Priority Setting Partnership (PSP). During the PSP process, we collaborated with people with lived experience of stroke and stroke professionals to find out what they thought were the top priorities in stroke research. From this, we identified the top ten priorities in two areas: prevention, diagnosis and short-term care, and rehabilitation and long-term care.

Now, when researchers apply to us for funding, we require that their work addresses at least one of these priorities, or a priority from the Childhood Neurological Disabilities PSP Top 10 as it relates to childhood stroke.

Jatinder’s project addresses the following priority from the Stroke PSP:

  • Prevention and acute care 3: Benefits and risks of treatments for bleeding strokes
  • Prevention and acute care 4: Benefits and risks of new therapies for stroke
  • Prevention and acute care 8: How can we reduce complications of stroke?

Meet the researcher

Jatinder is a Clinical Associate Professor of Stroke Medicine at the University of Leicester and an Honorary Consultant Stroke Physician at University Hospitals of Leicester NHS Trust. Alongside his clinical work, he has been researching the brain's blood flow supply for the last ten years.

Jatinder says, "This Senior Clinical Lectureship offers me a unique opportunity to inform the next phase of ICH research through an innovative and exciting programme of work. I have positioned myself to maximise available resources here in Leicester and to succeed through developing into a strong ambassador for the Stroke Association in addition to a 'Citizen of Change' - an aspiration my institution has for all its affiliates. I've been labelled a 'rising star' amongst academic staff by the University of Leicester and I hope to continue to develop to achieve my potential here."

Jatinder is also keen to support other researchers and develop networks of people who can bridge the gaps between our current understanding of stroke, treatment and complications, and the overall outcome for patients. Working with a team including clinicians, research nurses, clinical physiologists, medical physicists and engineers, he hopes to make it possible for the NHS to use real-time personalised assessments to make better decisions about stroke treatment.